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Three subcategories of high-risk flat and depressed lesions (FDLs), laterally spreading tumors non-granular type (LST-NG), depressed lesions, and large sessile serrated lesions (SSLs), are highly attributable to post-colonoscopy colorectal cancer (CRC). Efficient and organized educational programs on detecting high-risk FDLs are lacking. We aimed to explore whether a web-based educational intervention with training on FIND clues (fold deformation, intensive stool/mucus attachment, no vessel visibility, and demarcated reddish area) may improve the ability to detect high-risk FDLs.This was an international web-based randomized control trial that enrolled non-expert endoscopists in 13 Asian countries. The participants were randomized into either education or non-education group. All participants took the pre-test and post-test to read 60 endoscopic images (40 high-risk FDLs, five polypoid, 15 no lesions) and answered whether there was a lesion. Only the education group received a self-education program (video and training questions and answers) between the tests. The primary outcome was a detection rate of high-risk FDLs.In total, 284 participants were randomized. After excluding non-responders, the final data analyses were based on 139 participants in the education group and 130 in the non-education group. The detection rate of high-risk FDLs in the education group significantly improved by 14.7% (66.6-81.3%) compared with -0.8% (70.8-70.0%) in the non-education group. Similarly, the detection rate of LST-NG, depressed lesions, and large SSLs significantly increased only in the education group by 12.7%, 12.0%, and 21.6%, respectively.Short self-education focusing on detecting high-risk FDLs was effective for Asian non-expert endoscopists. (UMIN000042348).

BackgroundThere were limited data on the risk of post-polypectomy bleeding (PPB) in patients on direct oral anticoagulants (DOAC). We aimed to evaluate the PPB and thromboembolic risks among DOAC and warfarin users in a population-based cohort.MethodsWe performed a territory-wide retrospective cohort study involving patients in Hong Kong from 2012 to 2020. Patients who received an oral anticoagulant and had undergone colonoscopy with polypectomy were identified. Propensity-score models with inverse probability of treatment weighting were developed for the warfarin-DOAC and between-DOAC comparisons. The primary outcome was clinically significant delayed PPB, defined as repeat colonoscopy requiring haemostasis within 30 days. The secondary outcomes were 30-day blood transfusion requirement and new thromboembolic event.ResultsApixaban was associated with lower PPB risk than warfarin (adjusted HR (aHR) 0.39, 95% CI 0.24 to 0.63, pFor thromboembolic events, apixaban was associated with lower risk than warfarin (aHR 0.22, 95% CI 0.11 to 0.45, pConclusionsApixaban was associated with a significantly lower risk of PPB and thromboembolism than warfarin, dabigatran and rivaroxaban, particularly in older patients with right-sided polyps.

Anti-thrombotics use is a significant risk factor of post-polypectomy bleeding (PPB). Evidence of prophylactic clipping is only available for proximal and large colonic lesions in general population. Dedicated studies to examine the benefit of prophylactic clipping in patients on aspirin remain scarce.A propensity-score weighted retrospective cohort study was performed in a tertiary referral center from January 2018 to September 2021. Patients who received aspirin and underwent colonoscopic polypectomy, endoscopic mucosal resection or endoscopic submucosal dissection were included. Data on baseline demographics, medications and endoscopic factors (polyp number, size, location, morphology, resection method and prophylactic clipping) were captured. Propensity-score weighting models were developed between prophylactic clipping and no clipping groups. The primary outcome was delayed PPB within 30 days, with a composite endpoint consisting of repeated colonoscopy for hemostasis, requirement of blood transfusion or hemoglobin drop of greater than 2g/dL.Total 1,373 patients with 3,952 polyps were included. Baseline characteristics were balanced between two groups. In the multivariate analysis, the largest polyp size was a significant risk factor for PPB (odds ratio (OR) 1.07, 95%CI 1.02-1.11, p=0.002). Prophylactic clipping was not associated with a reduced risk of PPB (OR 1.34, 95%CI 0.83-2.18, p=0.240) and did not show any risk reduction in subgroups with different polyp sizes, locations and endoscopic resection techniques.Prophylactic clipping was not associated with a lower risk of PPB in aspirin users after endoscopic resection of colorectal polyps. Aspirin use should not be regarded as the only factor for the routine use of prophylactic clips.

This study evaluated teachers’ use of universal Program-Wide Positive Behavior Support (PW-PBS) practices at a class-wide level, the rate of disruptive behavior, and the level of academic engagement in Singapore preschool general education classrooms. Evaluation was carried out in 32 classrooms using mainly direct observational methods. Findings indicated that while the majority of the teachers taught rules and expectations to children several times throughout the year, used effective error corrections, and allocated more than 70% of class time to academic instructions, none of them had a system for documenting and rewarding appropriate child behavior, or a documented system to address specific behavioral violations. Very few teachers used a continuum of consequences to manage rule violations, and the use of general and behavior-specific praise was low. Furthermore, rates of disruptive behavior were relatively high, which were associated with high rates of reprimands, and one third of the classrooms had low academic engagement levels. Methods of enhancing teacher training in universal practices are discussed.

Alloimmune responses driven by donor-specific antibodies (DSAs) can lead to antibody-mediated rejection (ABMR) in organ transplantation. Yet, the cellular states underlying alloreactive B cell responses and the molecular components controlling them remain unclear. Using high-dimensional profiling of B cells in a cohort of 96 kidney transplant recipients, we identified expanded numbers of CD27+CD21– activated memory (AM) B cells that expressed the transcription factor T-bet in patients who developed DSAs and progressed to ABMR. Notably, AM cells were less frequent in DSA+ABMR– patients and at baseline levels in DSA– patients. RNA-Seq analysis of AM cells in patients undergoing ABMR revealed these cells to be poised for plasma cell differentiation and to express restricted IGHV sequences reflective of clonal expansion. In addition to T-bet, AM cells manifested elevated expression of interferon regulatory factor 4 and Blimp1, and upon coculture with autologous T follicular helper cells, differentiated into DSA-producing plasma cells in an IL-21–dependent manner. The frequency of AM cells was correlated with the timing and severity of ABMR manifestations. Importantly, T-bet+ AM cells were detected within kidney allografts along with their restricted IGHV sequences. This study delineates a pivotal role for AM cells in promoting humoral responses and ABMR in organ transplantation and highlights them as important therapeutic targets.

ObjectiveThe impact of faecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome is uncertain. We aimed to study whether combining FMT with lifestyle modification could enhance the engraftment of favourable microbiota in obese patients with type 2 diabetes mellitus (T2DM).DesignIn this double-blind, randomised, placebo-controlled trial, 61 obese subjects with T2DM were randomly assigned to three parallel groups: FMT plus lifestyle intervention (LSI), FMT alone, or sham transplantation plus LSI every 4 weeks for up to week 12. FMT solution was prepared from six healthy lean donors. Faecal metagenomic sequencing was performed at baseline, weeks 4, 16 and 24. The primary outcome was the proportion of subjects acquiring ≥20% of microbiota from lean donors at week 24.ResultsProportions of subjects acquiring ≥20% of lean-associated microbiota at week 24 were 100%, 88.2% and 22% in the FMT plus LSI, FMT alone, and sham plus LSI groups, respectively (pBifidobacterium and Lactobacillus compared with FMT alone (pConclusionRepeated FMTs enhance the level and duration of microbiota engraftment in obese patients with T2DM. Combining lifestyle intervention with FMT led to more favourable changes in recipients’ microbiota and improvement in lipid profile and liver stiffness.Trial registration numberNCT03127696.

Background The Coronavirus Disease 2019 (COVID-19) pandemic had a huge impact on healthcare systems globally. Decline in hospital admissions for common medical emergencies was observed. We investigated its collateral effect on hospitalizations and clinical outcomes in patients with gastrointestinal (GI) and liver diseases in Hong Kong. Methods We performed a territory-wide retrospective cohort study in Hong Kong from January 1, 2019, to May 31, 2020. Data were retrieved through Clinical Data Analysis and Reporting System. We included patients admitted to hospitals with top diagnoses of luminal GI cancers, pancreatico-hepatobiliary cancers, benign pancreaticobiliary disorders, liver diseases, non-infective enteritis and colitis, non-variceal and variceal upper gastrointestinal bleeding (UGIB). We excluded patient-based hospital admissions without emergency department attendance and length of stay equal to or shorter than one day. The primary endpoint was the total number of index hospital admissions related to these diagnoses at different time points. The secondary endpoints were in-hospital mortality, intensive care unit admission, elective or emergency operations and endoscopy. The COVID-19 period was defined as the time after the first local case in January 2020, week 4. Results We recorded a total of 195,867 hospital admissions related to GI diseases during the study period, and 125,049 of them were included in the final analysis. Comparing the same pre-COVID19 and COVID-19 periods, we observed a significant decline in the average number of hospitalizations for GI diseases (17.0% reduction, P Conclusions The number of hospitalizations related to GI diseases reduced drastically during the COVID-19 epidemic, yet no excessive in-hospital mortality was observed. More emergency endoscopies and operations were required, particularly for UGIB and benign pancreaticobiliary conditions.

BACKGROUND: Although antibody-mediated rejection (ABMR) has been long recognized as a leading cause of allograft failure after kidney transplantation, the cellular and molecular processes underlying the induction of deleterious donor-specific antibody (DSA) responses remain poorly understood. METHODS: Using high-dimensional flow cytometry, in vitro assays, and RNA sequencing, we concomitantly investigated the role of T follicular helper (T(FH)) cells and B cells during ABMR in 105 kidney transplant recipients. RESULTS: There were 54 patients without DSAs; of those with DSAs, ABMR emerged in 20 patients, but not in 31 patients. We identified proliferating populations of circulating T(FH) cells and activated B cells emerging in blood of patients undergoing ABMR. Although these circulating T(FH) cells comprised heterogeneous phenotypes, they were dominated by activated (ICOS(+)PD-1(+)) and early memory precursor (CCR7(+)CD127(+)) subsets, and were enriched for the transcription factors IRF4 and c-Maf. These circulating T(FH) cells produced large amounts of IL-21 upon stimulation with donor antigen and induced B cells to differentiate into antibody-secreting cells that produced DSAs. Combined analysis of the matched circulating T(FH) cell and activated B cell RNA-sequencing profiles identified highly coordinated transcriptional programs in circulating T(FH) cells and B cells among patients with ABMR, which markedly differed from those of patients who did not develop DSAs or ABMR. The timing of expansion of the distinctive circulating T(FH) cells and activated B cells paralleled emergence of DSAs in blood, and their magnitude was predictive of IgG3 DSA generation, more severe allograft injury, and higher rate of allograft loss. CONCLUSIONS: Patients undergoing ABMR may benefit from monitoring and therapeutic targeting of T(FH) cell–B cell interactions.

BACKGROUND Children with developmental disabilities tend to develop challenging behaviours. Parenting programmes that focus on behaviour management may help parents address these difficult behaviours by increasing parenting self-efficacy. However, the literature on parenting self-efficacy is still limited due to measurement variability in conceptualization and operationalization of the construct, and heavy reliance on cross-sectional data. METHOD This study utilized hierarchical linear regression to examine the predictors of parenting self-efficacy in 284 mothers who attended a parenting programme in a hospital's Department of Child Development in Singapore. RESULTS Our model was able to explain 37% of variance in parenting self-efficacy. After controlling for general stress and specific parenting hassles, the programme was still found to be effective in improving mothers' parenting self-efficacy. CONCLUSIONS Results are discussed in terms of their implications for developing a model for parenting self-efficacy, and possible improvements to be made on the parenting programme.

It is recommended that patients with acute upper gastrointestinal bleeding undergo endoscopy within 24 hours after gastroenterologic consultation. The role of endoscopy performed within time frames shorter than 24 hours has not been adequately defined.To evaluate whether urgent endoscopy improves outcomes in patients predicted to be at high risk for further bleeding or death, we randomly assigned patients with overt signs of acute upper gastrointestinal bleeding and a Glasgow-Blatchford score of 12 or higher (scores range from 0 to 23, with higher scores indicating a higher risk of further bleeding or death) to undergo endoscopy within 6 hours (urgent-endoscopy group) or between 6 and 24 hours (early-endoscopy group) after gastroenterologic consultation. The primary end point was death from any cause within 30 days after randomization.A total of 516 patients were enrolled. The 30-day mortality was 8.9% (23 of 258 patients) in the urgent-endoscopy group and 6.6% (17 of 258) in the early-endoscopy group (difference, 2.3 percentage points; 95% confidence interval [CI], -2.3 to 6.9). Further bleeding within 30 days occurred in 28 patients (10.9%) in the urgent-endoscopy group and in 20 (7.8%) in the early-endoscopy group (difference, 3.1 percentage points; 95% CI, -1.9 to 8.1). Ulcers with active bleeding or visible vessels were found on initial endoscopy in 105 of the 158 patients (66.4%) with peptic ulcers in the urgent-endoscopy group and in 76 of 159 (47.8%) in the early-endoscopy group. Endoscopic hemostatic treatment was administered at initial endoscopy for 155 patients (60.1%) in the urgent-endoscopy group and for 125 (48.4%) in the early-endoscopy group.In patients with acute upper gastrointestinal bleeding who were at high risk for further bleeding or death, endoscopy performed within 6 hours after gastroenterologic consultation was not associated with lower 30-day mortality than endoscopy performed between 6 and 24 hours after consultation. (Funded by the Health and Medical Fund of the Food and Health Bureau, Government of Hong Kong Special Administrative Region; ClinicalTrials.gov number, NCT01675856.).

ObjectiveWhile it is recommended that patients presenting with acute upper gastrointestinal bleeding (AUGIB) should receive endoscopic intervention within 24 hours, the optimal timing is still uncertain. We aimed to assess whether endoscopy timing postadmission would affect outcomes.DesignWe conducted a retrospective, territory-wide, cohort study with healthcare data from all public hospitals in Hong Kong. Adult patients (age ≥18) that presented with AUGIB between 2013 and 2019 and received therapeutic endoscopy within 48 hours (n=6474) were recruited. Patients were classified based on endoscopic timing postadmission: urgent (t≤6), early (6ResultsResults showed that urgent timing (n=1008) had worse outcomes compared with early endoscopy (n=3865), with higher 30-day all-cause mortality (pConclusionCompared with urgent and late endoscopy among patients who have received therapeutic endoscopies, early endoscopy was associated with superior outcomes especially among patients with non-variceal bleeding. This supports the notion that non-variceal AUGIB patients should receive endoscopy within 24 hours, but also emphasises the importance of prior resuscitation and pharmacotherapy.

Esophageal squamous cell carcinoma (ESCC) is a deadly disease, partly because it is often diagnosed late in disease stage. An accurate early diagnosis by endoscopy could detect advanced carcinoma as well as curable dysplasia and early ESCC. This could save patients from incurable advanced malignancy. Important progress has been made in high-quality endoscopic diagnosis, including magnifying endoscopy, narrowband imaging, and other image enhancement, as well as in techniques in endoscopic resection. These emerging techniques will aid the early diagnosis of ESCC that lead to higher chance of curing the cancer.

The clinical outcome of upper gastrointestinal bleeding has improved due to advances in endoscopic therapy and standardized peri-endoscopy care. Apart from validating clinical scores, artificial intelligence-assisted machine learning models may play an important role in risk stratification. While standard endoscopic treatments remain irreplaceable, novel endoscopic modalities have changed the landscape of management. Over-the-scope clips have high success rates as rescue or even first-line treatments in difficult-to-treat cases. Hemostatic powder is safe and easy to use, which can be useful as temporary control with its high immediate hemostatic ability. After endoscopic hemostasis, Doppler endoscopic probe can offer an objective measure to guide the treatment endpoint. In refractory bleeding, angiographic embolization should be considered before salvage surgery. In variceal hemorrhage, banding ligation and glue injection are first-line treatment options. Endoscopic ultrasound-guided therapy is gaining popularity due to its capability of precise localization for treatment targets. A self-expandable metal stent may be considered as an alternative option to balloon tamponade in refractory bleeding. Transjugular intrahepatic portosystemic shunting should be reserved as salvage therapy. In this article, we aim to provide an evidence-based comprehensive review of the major advancements in endoscopic hemostatic techniques and clinical outcomes.

Esophageal squamous cell carcinoma (ESCC) is a deadly disease, partly because it is often diagnosed late in disease stage. An accurate early diagnosis by endoscopy could detect advanced carcinoma as well as curable dysplasia and early ESCC. This could save patients from incurable advanced malignancy. Important progress has been made in high-quality endoscopic diagnosis, including magnifying endoscopy, narrowband imaging, and other image enhancement, as well as in techniques in endoscopic resection. These emerging techniques will aid the early diagnosis of ESCC that lead to higher chance of curing the cancer.

We conducted a single-centre, retrospective study for all consecutive cases of recurrent or refractory CDI who underwent FMT from 2013 to 2018. Clinical demographics, outcome, and safety parameters were collected.A total of 24 patients with recurrent or refractory CDI (median age 70 years, interquartile range=45.0-78.3 years; 67% male) were included. Over 80% had been recently hospitalised or were long-term care facility residents. Faecal microbiota transplantation was delivered by feeding tube in 11 (45.8%), oesophagogastroduodenoscopy in eight (33.3%), and colonoscopy in six (25%) of the patients. Resolution of diarrhoea without relapse within 8 weeks was achieved in 21 out of 24 patients (87.5%) after FMT. No deaths occurred within 30 days. The FMT was well tolerated and no serious adverse events attributable to FMT were reported.Our results confirm that FMT is a safe, efficacious, and feasible intervention for patients with refractory or recurrent CDI in Hong Kong. Given the increasing disease burden and the lack of effective alternatives in Hong Kong for difficult-to-treat cases of CDI, we recommend that a territory-wide FMT service be established to address increasing demand for this treatment.

Introduction Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infection globally, causing significant morbidity and mortality. Faecal microbiota transplantation (FMT) has emerged as a promising option for recurrent and refractory CDI. This study aimed to assess the safety, efficacy, and feasibility of FMT for CDI in Hong Kong. Methods We conducted a single-centre, retrospective study for all consecutive cases of recurrent or refractory CDI who underwent FMT from 2013 to 2018. Clinical demographics, outcome, and safety parameters were collected. Results A total of 24 patients with recurrent or refractory CDI (median age 70 years, interquartile range=45.0-78.3 years; 67% male) were included. Over 80% had been recently hospitalised or were long-term care facility residents. Faecal microbiota transplantation was delivered by feeding tube in 11 (45.8%), oesophagogastroduodenoscopy in eight (33.3%), and colonoscopy in six (25%) of the patients. Resolution of diarrhoea without relapse within 8 weeks was achieved in 21 out of 24 patients (87.5%) after FMT. No deaths occurred within 30 days. The FMT was well tolerated and no serious adverse events attributable to FMT were reported. Conclusion Our results confirm that FMT is a safe, efficacious, and feasible intervention for patients with refractory or recurrent CDI in Hong Kong. Given the increasing disease burden and the lack of effective alternatives in Hong Kong for difficult-to-treat cases of CDI, we recommend that a territory-wide FMT service be established to address increasing demand for this treatment.

Non-alcoholic fatty liver disease (NAFLD) is an increasingly important cause of chronic liver disease globally. Similar to metabolic syndrome and obesity, NAFLD is associated with alternations in the gut microbiota and its related biological pathways. While the exact pathophysiology of NAFLD remains largely unknown, changes in intestinal inflammation, gut permeability, energy harvest, anaerobic fermentation and insulin resistance have been described. In this chapter, we review the relationship between the gut microbiota, obesity and NAFLD, and highlight potential ways to modify the gut microbiota to help managing NAFLD patients.

PURPOSE: The purpose of this study is to evaluate the efficacy and safety of botulinum toxin injection as a primary treatment for strabismus in a cohort of patients with nasopharyngeal carcinoma (NPC)-related chronic sixth nerve palsy. PATIENTS AND METHODS: We retrospectively reviewed all cases of NPC-related sixth nerve palsy receiving botulinum toxin injection in the Hong Kong Eye Hospital between January 2009 and January 2016. Only cases with diplopia for at least 6 months; and failed a trial of Fresnel prism therapy were recruited. We excluded cases with prior strabismus surgery and multiple cranial nerve palsies. Patients were offered botulinum toxin injection as primary treatment for their strabismus and were given further injections or offered surgery if diplopia persisted. Success with botulinum toxin was defined as a final distant orthophoria of

Non-alcoholic fatty liver disease (NAFLD) is an increasingly important cause of chronic liver disease globally. Similar to metabolic syndrome and obesity, NAFLD is associated with alternations in the gut microbiota and its related biological pathways. While the exact pathophysiology of NAFLD remains largely unknown, changes in intestinal inflammation, gut permeability, energy harvest, anaerobic fermentation and insulin resistance have been described. In this chapter, we review the relationship between the gut microbiota, obesity and NAFLD, and highlight potential ways to modify the gut microbiota to help managing NAFLD patients.

Background The Signposts for Building Better Behaviour program, developed by the Parenting Research Centre, Victoria, Australia, was conducted at a public hospital facility in Singapore.Method More than 1,000 parents completed the program, and filled in questionnaires about their child's behaviours.Results Parents rated themselves in the questionnaires as being significantly less hassled, stressed, depressed, and anxious after attending the program. They were more confident and satisfied with managing their child, and rated their children's behaviours as having improved. Effect sizes ranged from 0.12 to 0.59. The findings were maintained 3 months after completion of the program.Conclusions The study provides evidence of the cross-cultural applicability of the principles underlying the Signposts program. As there are long-term repercussions when children's behaviour problems are not dealt with appropriately, such behaviour management programs should be made more available to parents and caregivers.

Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), superoxide anion (O2(-)), and hydroxyl radical (OH(•)) have been implicated in mediating various pathological events such as cancer, atherosclerosis, diabetes, ischemia, inflammatory diseases, and the aging process. The glutathione (GSH) redox cycle and antioxidant enzymes-superoxide dismutase (SOD) and catalase (CAT)-play an important role in scavenging ROS and preventing cell injury. Pycnogenol has been shown to protect endothelial cells against oxidant-induced injury. The present study determined the effects of pycnogenol on cellular metabolism of H2O2 and O2(-) and on glutathione-dependent and -independent antioxidant enzymes in bovine pulmonary artery endothelial cells (PAEC). Confluent monolayers of PAEC were incubated with pycnogenol, and oxidative stress was triggered by hypoxanthine and xanthine oxidase or H2O2. Pycnogenol caused a concentration-dependent enhancement of H2O2 and O2(-) clearance. It increased the intracellular GSH content and the activities of GSH peroxidase and GSH disulfide reductase. It also increased the activities of SOD and CAT. The results suggest that pycnogenol promotes a protective antioxidant state by upregulating important enzymatic and nonenzymatic oxidant scavenging systems.

Lycopene, a red pigmented carotenoid present in many fruits and vegetables such as tomatoes, has been associated with the reduced risk of breast cancer. This study sought to identify proteins modulated by lycopene during cell proliferation of the breast cancercell line MCF-7 to gain an understanding into its mechanism of action. MCF-7 breast cancercells and MCF-10 normal breast cells were treated with 0, 2, 4, 6, 8, and 10mM of lycopene for 72h. 3-(4,5-Dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) tetrazolium reduction assay was used to measure cell proliferation and twodimensional fluorescence difference gel electrophoresis to assess the changes in protein expression, which were identified using MALDI-ToF/ToF (matrix-assisted laser desorption ionization tandem time-of-flight) and Mascot database search. MTTand cell proliferation assays showed that lycopene selectively inhibited the growth of MCF-7 but not MCF-10 cells. Difference gel electrophoresis analysis revealed that proteins in the MCF-7 cells respond differently to lycopene compared with the MCF-10 cells. Lycopene altered the expression levels of proteins such as Cytokeratin 8/18 (CK8/18), CK19 and their post translational status. We have shown that lycopene inhibits cell proliferation in MCF-7 human breast cancercells but not intheMCF-10 mammaryepithelial cells. Lycopenewas shown to modulatecell cycleproteins such as beta tubulin, CK8/18, CK19 and heat shock proteins. Copyright © 2012 John Wiley & Sons, Ltd.

‘Slotting fee’ (hereafter ‘SF’) is an upfront fee a ‘supplier’ is required to pay a retailer in order to have his product sold on the retailer's shelves. It is becoming increasingly common, but also widely reviled. This paper considers a newsvendor product whose expected demand is dependent on retail price and sales effort. The question we pose is: given that the Stackelberg-dominant retailer has to choose a pricing contract with which she transacts with the supplier, how would the supply-chain stakeholders fare when the retailer implements SF instead of another practical pricing contract? We show that, contradicting its negative public image, SF empowers the dominant retailer to specify contract terms that will benefit all the stakeholder-groups. That is, the supplier's and the retailer's profits are higher, the production workers are asked to produce more, and the consumers pay a lower retail price. We also propose a new ‘composite’ contract format that incorporates both the SF and ‘buyback’ features. This composite format empowers the retailer to provide even greater benefits to the supply-chain's stakeholders.

To report the surgical outcomes of 24 patients undergoing single-staged three horizontal muscles squint surgery for extra-large angle exotropia.Prospective case series of 24 consecutive patients with primary exotropia60 prism diopters (PD) at distant and underwent single-staged three horizontal muscles squint surgery from 2003 to 2006. Surgery consisted of bilateral lateral rectus recession of 9.0 mm for 50 PD exotropic correction. For every 5 PD remaining angle exceeding 50 PD, we additionally performed 1.0 mm of unilateral medial rectus resection. The mean follow-up period was 15.8 months (range 6.0-38.0 months; SD 9.5 months).The mean age at surgery was 31.2 years old (range 7-78 years old, SD 18.2 years old). The mean distant preoperative deviation was 71.3 PD (range 60-85 PD, SD 7.7 PD). No limitation of eye movement or diplopia was found. The success rate was higher in the intermittent group (88.2%) than the constant group (42.9%) (P=0.02) and in cases with preoperative deviation of80 PD (84.2%) compared with those with deviationor=80 PD (40.0%) (P=0.042).Measurement of preoperative deviation and the surgery for extra-large angle exotropia made management of this condition difficult. Single-staged three horizontal muscles squint surgery can be one of the options. Further researches on management of exotropia of80 PD are warranted.

By using an extended version of R. Treiman, M. Cassar, and A. Zukowski's (1994) flaps spelling task (wa_er, is it t or d in water?), the authors investigated the metalinguistic awareness of 6-year-old bilingual children from 3 different language backgrounds (LBs): English-LB (English-L1, Mandarin-L2), Chinese-LB (Mandarin-L1, English L2), and Malay-LB (Bahasa Malaysia-L1, English-L2). Treiman et al. found that unilingual English-speaking children's performance was poorer on flapped words than on control words and better on /d/ flaps than on /t/ flaps, suggesting phonology is salient even for beginners. The data for bilinguals revealed predictable group differences in the use of orthographic and phonological awareness for early spellings, even though the children were all attending the same English-medium kindergarten. Possible educational implications for linguistic minority children are briefly discussed.

Purpose. To evaluate and compare the effectiveness of scleral fixation SR and LR union suture and nonscleral fixation union suture for the treatment of myopic strabismus fixus.Methods. Retrospective review of 32 eyes of 22 patients with myopic strabismus fixus who had undergone union suture of superior rectus (SR) and lateral rectus (LR) with or without scleral fixation, and follow-up longer than 6 months at Hong Kong Eye Hospital from 2006 to 2013. Surgical techniques and outcomes in terms of ocular alignment are analyzed.Results. There is significant overall improvement both in postoperative angle of esodeviation (P<0.01) and postoperative range of movement (P=0.042). Comparing between the sclera fixation group (11 eyes) versus nonscleral fixation group (21 eyes), the postoperative horizontal deviation, the postoperative vertical deviation, successful outcome, and the change in horizontal deviation were not significantly different (P>0.05).Conclusions. Union suture of SR and LR is an effective procedure in correcting myopic strabismus fixus. Fixation of the union suture to the sclera does not improve surgical outcome.

We previously reported that Pycnogenol , procyanidins extracted from the bark of French maritime ® pine (Pinus maritima Aiton; the official botanical name is now Pinus pinaster Aiton) is a potent free radical scavenger. It has been shown to inhibit macrophage oxidative burst. Macrophages carry out their microbicidal and tumoricidal activities via oxygen-dependent and oxygen-independent mechanisms. The present study investigated the effects of Pycnogenol on oxygen-independent killing mechanisms of macrophages, with ® ® and IL-1β. These results suggest that Pycnogenol can enhance the macrophage function by increasing its ® ability to phagocytosis and secretion of TNF-α and IL-1β. These two cytokines may provide costimulatory signals to enhance both the humoral and cellular immune responses to promote host defense.

Two retinoblastoma patients underwent uneventful enucleations while undergoing perioperative chemotherapy. In both cases the postoperative course was complicated by poor conjunctival wound healing. Administration of topical autologous serum was associated with wound healing and conjunctivalization of these wounds.

Oxidative modification of LDL has been recognized as playing an important role in the initiation and progression of atherosclerosis. In this study, we determined the effects of aged garlic extract (AGE) and its major compound, S-allylcysteine (SAC), on oxidized LDL (Ox-LDL)-induced injury in endothelial cells (EC). Lactate dehydrogenase (LDH) release as an index of membrane damage, methylthiazol tetrazoium (MTT) assay for cell viability and thiobarbituric acid reactive substances (TBARS) indicating lipid peroxidation were measured. Ox-LDL caused an increase of LDH release, loss of cell viability and TBARS formation. Both AGE and SAC prevented all of these changes. To elucidate the mechanism, effects of AGE or SAC on intracellular glutathione (GSH) level in EC, and release of peroxide from EC and macrophages (M Phi) were determined. Ox-LDL depleted intracellular GSH and increased release of peroxides. Both AGE and SAC inhibited these changes. Effects of SAC on hydrogen peroxide (H(2)O(2)) or tumor necrosis factor (TNF)-alpha-induced nuclear factor (NF)-kappa B activation were determined. Pretreatment of EC with SAC inhibited NF-kappa B activation. We demonstrated that both AGE and SAC can protect EC from Ox-LDL-induced injury by preventing intracellular GSH depletion in EC and by minimizing release of peroxides from EC and M Phi. SAC also inhibited H(2)O(2)- or TNF-alpha-induced NF-kappa B activation. Our data suggest that AGE and its main compound, SAC, may be useful for prevention of atherosclerosis.

Pycnogenol (procyanidins extracted from the bark of Pinus maritima Aiton) is a potent free radical scavenger. In this study, we used macrophages (a major cell type in inflammation) to study the antiinflammatory effect of pycnogenol. We determined the effects of pycnogenol on peroxide generation and on glutathione (GSH)-dependent and GSH-independent antioxidant systems. J774 cells were incubated with pycnogenol at 37°C and 5% CO 2 for 2 h. Generation of peroxides (one of the major mediators of inflammation) was triggered by zymosan and measured with a fluorometric assay. Pycnogenol exhibited a concentration-dependent suppression of peroxide release. To investigate possible mechanisms involved in pycnogenol's suppression of peroxide release, confluent monolayers of J774 cells were incubated with pycnogenol for 18 h, washed, resuspended in phosphate buffered saline, and sonicated to obtain a cell lysate. Biochemical assays were performed with the lysate. Pycnogenol increased the intracellular GSH content and activities of GSH peroxidase and GSH disulfide reductase, indicating its ability to modulate the GSH redox cycle. The activity of antioxidant enzymes catalase and superoxide dismutase also increased with pycnogenol treatment. These results suggest that the antiinflammatory effect of pycnogenol may at least in part be due to its ability to modulate the GSH redox cycle and activities of catalase and superoxide dismutase.

Purpose. In recent years the attitudes and practices of euthanasia (E) and physician‐assisted suicide (PAS) among health care workers have been evaluated in different countries. There is, however, still an information gap on the role of pharmacists in these matters. The aim of our study was to study the attitudes and practices of E and PAS among pharmacists.Methodology. We conducted a nation‐wide survey into the practice, including adherence to guidelines, of E and PAS in community and hospital pharmacies (CP and HP) in the Netherlands. Furthermore, the attitude of community pharmacists concerning this subject was evaluated. Anonymous questionnaires were sent to a random sample of 50% (n=755) of all CP and to all (n=101) HP.Results. The response rates were 52% and 51% for CP and HP, respectively. Most of the CP‐respondents (95%) agreed with the concept of E and PAS and would dispense drugs for these purposes. When the data were extrapolated to all pharmacies, there were 1351 and 340 dispensings of drugs for E and PAS per year in CP and HP (94% of all requests), respectively. In most cases the pharmacist had been notified of the condition of the patient (CP: 93%, HP 87%) and a written request was obtained (CP: 74%, HP: 79%). The drugs were often handed personally to the physician (CP: 98%, HP: 86%). Involvement of pharmacy technicians was more common in HP than in CP (31% versus 6%). The most frequently dispensed drugs were muscle relaxants with barbiturates (CP: 47%, HP 71%), barbiturates only (CP: 19%, HP: 6.1%), and muscle relaxants with benzodiazepines (CP: 14%, HP: 7.6%).Conclusion. Most pharmacists are supportive of E and PAS and are prepared to fill prescriptions written for these purposes.

The present study determined the effects of Ginkgo biloba extract (GBE) on the activation of nuclear factor kappa B (NF-kappaB) and the level of hydrogen peroxide (H2O2) in bovine pulmonary artery endothelial cells (PAEC). H2O2 showed a concentration-dependent activation of NF-kappaB. GBE demonstrated a concentration-dependent suppression of NF-kappaB activated by H2O2. GBE directly scavenged H2O2 in a cell-free system; it also decreased H2O2 levels in PAEC. These results suggest that the inhibitory effect of GBE on H2O2-induced NF-kappaB activation may be caused by its scavenging and suppression of H2O2. Our experiments demonstrate that GBE can inhibit NF-kappaB activation induced by H2O2 and may thus be effective for the prevention or treatment of atherosclerosis and other disorders related to NF-kappaB activation.

The amino-carbonyl (Maillard) reaction of amino acids with sugars is a nonenzymatic browning reaction that takes place during the processing, cooking, and storage of foods. Maillard reaction products (MRPs) have been shown to possess interesting chemical and biological properties including antimutagenic and antioxidant activity. In this study, we determined the antioxidant effects of fructosyl arginine (Fru-Arg), a MRP in aged garlic extract. Low density lipoprotein (LDL) was incubated with Cu(2+) at 37 degrees C and 5% CO(2) for 24 hours, which resulted in an increase of thiobarbituric acid reactive substances (TBARS) indicating lipid peroxidation. Coincubation of Cu(2+) with Fru-Arg and LDL resulted in a significant inhibition of TBARS formation. Pulmonary artery endothelial cells (PAEC) were exposed to 0.1 mg/mL oxidized LDL (Ox-LDL) at 37 degrees C and 5% CO(2) for 24 hours. Lactate dehydrogenase (LDH) release, as an index of cell membrane damage, and TBARS were measured. Ox-LDL caused an increase of LDH release and TBARS formation. Pretreatment of PAEC with Fru-Arg inhibited these changes. Murine macrophages were incubated with Ox-LDL, and the release of peroxides was measured using a fluorometric assay. Ox-LDL caused an increased release of peroxides. Coincubation of macrophages with Fru-Arg and Ox-LDL inhibited the release of peroxides dose-dependently. In a cell free system, Fru-Arg was shown to scavenge hydrogen peroxide. These data suggest that Fru-Arg is a potent antioxidant, and thus may be useful for the prevention of atherosclerosis and other disorders associated with oxidative stress.

Pycnogenol (procyanidins extracted from Pinus maritima) has been reputed as a potent free-radical scavenger and an antioxidant phytochemical. We previously reported that pycnogenol prevents vascular endothelial cells from injury induced by an organic oxidant t-butyl hydroperoxide. In this study, we determined the effects of pycnogenol on (a) oxidative burst of macrophages, (b) oxidation of plasma low density lipoprotein (LDL), and (c) hydroxyl radical-induced breakage of plasmid DNA. Pycnogenol was incubated with J774 murine macrophages at 37 degrees C and 5% CO2 and oxidative burst was triggered by zymosan. The intensity of fluorescence was measured. Pycnogenol exhibited a concentration-dependent inhibition of oxidative burst. CuSO4 was used to oxidize human plasma LDL and the formation of thiobarbituric acid reactive substances (TBARS) was determined. Co-incubation with pycnogenol resulted in a concentration-dependent inhibition of LDL oxidation. Exposure of pBR322 plasmid DNA to iron/ascorbic acid system resulted in cleavage/damage of DNA by hydroxyl radical, measured by agarose gel electrophoresis. Pycnogenol significantly minimized this cleavage. The results indicate that pycnogenol exhibits an extensive antioxidant effect in all three in vitro systems.

The antioxidant effect of a Chinese medicinal herb, Fructus corni extract (FCE), was investigated using models of oxidative stress in macrophages and vascular endothelial cells. Murine macrophages (J774) were incubated with FCE at 37°C and 5% CO2 for 1 hr. Oxidative burst was triggered by zymosan and measured with a fluorescent probe. FCE exhibited a concentration- dependent suppression of oxidative burst. Confluent monolayers of bovine pulmonary artery endothelial cells (PAEC) were preincubated with FCE for 20 hrs, washed, and then exposed to an organic oxidant t-butyl hydroperoxide (tBHP) for 2 hrs. Cell viability was assessed by methylthiazol tetrazolium (MTT) assay, and cell injury by the release of intracellular lactate dehydrogenase (LDH). Lipid peroxidation products of PAEC were determined by measuring thiobarbituric acid-reactive substances (TBARS). Exposure of PAEC to tBHP resulted in decreased cell viability, increased LDH release, and elevated TBARS. Preincubation of PAEC with FCE significantly reversed these changes. Our results demonstrated that FCE can protect vascular endothelial cells from oxidant injury. The data thus suggest that Fructus corni may be useful for the prevention and/or treatment of disorders associated with oxidative damage.

Oxygen free radicals have been implicated in mediating various pathological processes such as ischemia, inflammatory diseases, diabetes, and atherosclerosis. The antioxidant enzymes—superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX)—play an important role in scavenging oxidants and preventing cell injury. Aged Garlic Extract (AGE) has been shown to prevent oxidant-induced injury of endothelial cells. The present study determined the effects of AGE on the generation of hydrogen peroxide (H 2 O 2 ) and superoxide anion (O 2 − ) and the activity of three antioxidant enzymes in bovine pulmonary artery endothelial cells (PAEC). Confluent monolayers of PAEC were incubated with AGE, and oxidative stress was triggered by hypoxanthine and xanthine oxidase or H 2 O 2 . AGE exhibited both concentration- and time-dependent suppression of H 2 O 2 and O 2 − generation, and it also significantly increased the activities of SOD, CAT and GPX. The results suggest that AGE may be an effective antioxidant in preventing or treating disorders related to endothelial cell injury associated with free radicals.

This paper is an exploratory study of a very common variation of the classical newsboy problem: in addition to the supply at the beginning of the sales period, an additional replenishment opportunity exists sometime during the sales period. A basic model for the problem is presented and a semi-analytical solution procedure is developed. Numerical solutions obtained reveal certain interesting properties of the model. The paper shows that the replenishment extension makes the newsboy problem much more challenging managerially and also that it can be practically solved with significant profit implications.

Oxidation of low density lipoprotein (LDL) has been recognized as playing an important role in the initiation and progression of atherosclerosis. In this study, the effects of aged garlic extract and one of its major compounds, S-allylcysteine, on oxidized LDL-induced cell injury were studied. Pulmonary artery endothelial cells were pre-incubated with the garlic extract (1, 2.5 and 5 mg mL−) or 5-allylcysteine (01, 1, 10 and 20 mm) at 37°C and 5% CO2 for 24 h, washed, and then exposed to 01 mg mL− oxidized LDL for 24 h. Lactate dehydrogenase release as an index of membrane damage, methylthiazol tetrazolium assay for cell viability and thiobarbituric acid reactive substances indicating lipid peroxidation were determined. Preincubation of endothelial cells with the extract or S-allylcysteine significantly prevented membrane damage, loss of cell viability and lipid peroxidation. The data indicate that these compounds can protect vascular endothelial cells from injury caused by oxidized LDL, and suggest that they may be useful for prevention of atherosclerosis.

Reactive oxygen species are involved in signal transduction pathways leading to nuclear factor kappa B (NF-kappa B) activation which has been implicated in the regulation of gene transcription. We recently reported that a garlic compound, S-allyl cysteine (SAC), protects bovine pulmonary artery endothelial cells from oxidant injury induced by hydrogen peroxide (H2O2). In this study we determined the effects of SAC on NF-kappa B activation in human T lymphocytes (Jurkat cells) induced by tumor necrosis factor alpha (TNF- alpha) and H2O2. Activated NF-kappa B in nuclear extracts was measured by an electrophoretic mobility shift assay using 32P-labeled probe. SAC consistently exhibited a dose-dependent inhibition of NF-kappa B activation induced by both TNF-alpha and H2O2. Supershift with specific antibodies to NF-kappa B subunits confirmed that the inducible retarded bands observed in the EMSA and p65-p50 heterodimer of the NF-kappa B/Rel protein. Our data suggest that SAC may act via antioxidant mechanisms to block NF-kappa B activation in Jurkat cells.

Oxygen radical injury and lipid peroxidation have been suggested as major causes of cancer, atherosclerosis and the aging process. We examined in vitro the effect of garlic on H2O2-induced oxidant injury in bovine pulmonary artery endothelial cells (PAEC). After overnight preincubation with Aged Garlic Extract (AGE, from Wakunaga Pharmaceutical Co., Ltd., Japan) or S-allyl cysteine (SAC), PAEC monolayers were exposed to H2O2 for 3 h. Cell viability (MTT assay), lactate dehydrogenase (LDH) release, and lipid peroxidation (TBA-RS) were measured to assess oxidant injury. AGE (1-4 mg/ml) pretreatment significantly reduced the loss of cell viability induced by 50-100 microM of H2O2. AGE and SAC exhibited dose dependent inhibition of both LDH release and TBA-RS production induced by 50 microM of H2O2. The results show that AGE and SAC can protect vascular endothelial cells from oxidant injury. Numerous garlic compounds could be involved in the antioxidant properties of garlic, while there could be some prooxidant compounds derived from garlic. It is important to keep an array of antioxidant compounds to develop good herbal preparation, like AGE.

Nuclear factor kappa B (NF-kB), which has been implicated in the regulation of gene transcription, is essential for the expression of genes controlled by the long terminal repeat of human immunodeficiency virus type 1. Studies have shown that reactive oxygen species are involved in signal transduction pathways leading to NF-kB activation. We have reported that calf thymic peptides (TP) protect various cell types from oxidant injury. In this study, we determined the effects of TP on NF-d activation in human T lymphocytes (Jurkat cells) induced by two stimuli: tumor necrosis factor a and phorbol 12-myristate 13-acetate. Activated NF-kB in nuclear extracts was measured by an electrophoretic mobility shift assay (EMSA) using 32P-labeled probe. TP consistently exhibited a dose-dependent inhibition of NF-kB activation induced by both stimuli. Supershift with specific antibodies to NF-kB subunits confirmed that the inducible retarded bards observed in the EMSA are p6.5-p50 heterodimer of the NF-kB/Rel pr...

We recently reported that Ginkgo biloba extract (GBE) suppressed oxidative burst in macrophages and protected bovine pulmonary artery endothelial cells (PAEC) from oxidant injury. In this study the effects of GBE on glutathione (GSH) redox cycle and activity of antioxidant enzymes were investigated. Confluent monolayers of PAEC were incubated with GBE for 8–48 h, washed, and then lysed with Triton X-100. Biochemical assays were performed with the lysate. GBE caused both dose- and time-dependent increase in GSH level and glutathione disulfide (GSSG) reductase activity while GSH peroxidase and superoxide dismutase activity remained unaffected. Exposure of PAEC to an organic oxidant tert -butyl hydroperoxide ( t BHP) resulted in decreased GSH level, increased lipid peroxidation, and elevated leakage of intracellular lactate dehydrogenase. Preincubation or simultaneous treatment of PAEC with GBE prevented these changes induced by t BHP. Our data suggest that the antioxidant effect of GBE may be due to its modulation of the GSH redox cycle in PAEC as well as direct scavenging of the oxidant.

Studies on risk factors for drug non-compliance have not taken into account the possibility of correlated outcomes. We therefore conducted a study into risk factors for non-compliance by using analysis techniques that adjust for these correlations (longitudinal data analysis). Data were obtained from interviews and pharmacy records in a cross-sectional survey in Amsterdam. The subjects were 157 elderly people aged 70 years or older. Of these subjects, 37 were residents of a home for the elderly, 40 were community-dwelling elderly who needed to be visited regularly by a district nurse, and 80 were community-dwelling elderly who did not need to be visited by a district nurse. Most drugs (78%) were used according to the directions; the remainder (22%) were not used as intended. Odds ratios (95% confidence intervals) for non-compliance for moderate and poor/wrong knowledge of the purpose of a drug as compared with good/correct knowledge were 2.8 (1.2-6.7) and 4.2 (1.5-12), respectively. Drug regimens of two times daily and more than two times daily were associated with odds ratios for non-compliance of 4.5 (1.6-12) and 4.2 (1.7-11), respectively, compared to a regimen of once daily. Compliance increased if a drug was prescribed by a specialist instead of a general practitioner odds ratio 0.1 (0.04-0.4)]. There was no significant relation between compliance and the number of drugs prescribed to a patient, sex, age, living situation, patient group, or perceived effect. This study, which was based on longitudinal data analysis, demonstrates that in elderly people non-compliance with drug therapy is related to the knowledge of purpose of a drug, the complexity of a drug regimen, and the type of prescriber. The positive association between compliance and the number of drugs prescribed found in former studies was not confirmed.