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Investigation of drug-microbial interactions has gained prominence due to the increasing need to study pharmacomicrobiomics. Previous research has revealed the microbiome's role in drug metabolism, influencing efficacy, bioavailability, and toxicity. Several potential interactions have reported between drugs and microbes, including bioaccumulation, biotransformation, and the influence of drugs on microbial growth. To facilitate the investigation of drug-microbial interactions, in this study, we present an integrated platform and procedure for investigating drug-microbial interactions, focusing on biotransformation, bioaccumulation, metabolomics, exometabolomics, lipidomics, and exolipidomics. To illustrate the feasibility of this platform, we examined the interactions between digoxin and Lactiplantibacillus pentosus (L. pentosus), revealing previously unknown interactions. Although the growth of L. pentosus was unaffected by digoxin, metabolomics, exometabolomics, lipidomics, and exolipidomics analyses revealed digoxin's impact on metabolites and lipids inside and outside L. pentosus. Additionally, we utilized a validated liquid chromatography-mass spectrometry quantification platform to evaluate digoxin biotransformation and bioaccumulation levels by L. pentosus. After accurately quantifying digoxin in the supernatant and pellet, we determined that approximately 8.7 % of digoxin was biotransformed by L. pentosus. Exolipidomics analysis further supported digoxin biotransformation, identifying digoxigenin and its metabolites. These findings elucidate the potential impact of L. pentosus on digoxin metabolism, underscoring the importance of considering microbial interactions in pharmacological research. We anticipate that the integrated platform could assist in more pharmacomicrobiomics studies and uncover unknown drug-microbial interactions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hsiao-Wei Liao reports financial support was provided by Ministry of Science and Technology of Taiwan. Hsiao-Wei Liao reports a relationship with Ministry of Science and Technology of Taiwan that includes: funding grants., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To quantify post-cataract surgery health care utilization caused by dry eye symptoms (DES) and identify preoperative risk factors and mediators of postoperative DES., Setting: An outpatient surgical centre in Toronto, Canada., Design: Retrospective cohort study., Participants: Included patients had cataract surgery between April 2019 and January 2020, completed a preoperative Dry Eye Questionnaire 5 (DEQ5), and were over age 18., Methods: Data collected included DES risk factors, prophylaxis, and intraoperative and postoperative details. DES health care utilization and prevalence were reported as percentages. Risk of DES follow-up with DES prophylaxis use, and within each DEQ5 severity group, were analyzed with χ 2 -square test of independence and odds ratios. Binomial logistic regression assessed for significance of multiple preoperative and intraoperative risk factors, controlling for one another., Results: Of 1074 patients (46% male, mean age: 71, mean DEQ5: 5.12), 18.1% had at least one nonroutine postoperative appointment due to DES. Patients with moderate/severe DEQ5 scores were 1.843 times likelier to have postoperative DES concerns than those with no/mild scores (CI = 1.307-2.599). Preoperative DES prophylaxis did not reduce DES risk in any severity group. Higher DEQ5 score, female sex, bilateral sequential surgeries, and femtosecond laser-assisted cataract surgery had higher likelihood of postoperative DES (B = 0.054; p < 0.001; B = -0.351; p = 0.037; B = 0.695; p = 0.003; B = 0.491; p = 0.003, respectively)., Conclusion: Nearly 1 in 5 patients had DES postcataract surgery, with 1 in 12 requiring one or more nonroutine follow-ups for DES, suggesting substantial health care burden. Current standard preoperative DES treatment may not reduce postoperative DES, and further studies are needed to elucidate why., (Copyright © 2024 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess pain perception in patients undergoing manual cataract surgery versus femtosecond laser-assisted cataract surgery (FLACS) and pain perception of patients receiving anaesthesia at 2 different time points during the FLACS procedure. We also aimed to assess the factors affecting pain perception in these different study groups., Design: Prospective cohort comparison of patient-selected surgical approach., Participants: Patients undergoing delayed sequential bilateral cataract surgery at an ambulatory surgical centre in Ontario., Methods: Patients were assigned to 3 groups: a manual cataract surgery cohort (n = 30) and 2 FLACS cohorts, those who received neurolept anaesthesia just prior to draping for phacoemulsification (FLACS standard cohort; n = 38) and those who received neurolept anaesthesia prior to the femtosecond laser part of the procedure (FLACS early cohort; n = 35). Outcome metrics included pain scores on the visual analogue scale on postoperative day 0 and at postoperative week 1. Secondary outcome measures included anxiety scores, surgeon or anaesthesiologist patient cooperation scores, ocular metrics, and perioperative systemic vitals., Results: There were no significant differences in pain perception on postoperative day 0 and at postoperative week 1 among the manual cataract surgery and FLACS standard cohorts (p = 0.94 and p = 0.72, respectively) or FLACS early and FLACS standard cohorts (p = 0.76 and p = 0.67, respectively). Patients had higher pain scores during second-eye procedures than first-eye procedures., Conclusions: Cataract surgery technique or timing of anaesthesia for FLACS procedures does not affect pain perception postoperatively. Second-eye procedures are associated with higher pain scores than first-eye procedures., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Metabolomics has become a promising method for understanding pathological mechanisms. Plasma (PLS) is the most common sample type used for metabolomics studies, and dried blood spot (DBS) sampling has been regarded as a good strategy due to its unique characteristics. However, how results obtained from DBS can be correlated to results obtained from PLS remains unclear. To bridge the results and to investigate the feasibility of using DBS to study metabolomics, we performed a comparative study using 64 paired PLS and DBS samples. The number of features extracted from the two different sample types was investigated. The concentration correlations of the identified metabolites between the DBS and PLS were individually studied. Approximately 47 % showed a strong correlation, 19 % showed a moderate correlation, and 34 % showed a low or even negligible correlation. Finally, we applied both PLS- and DBS-based metabolomics to explore the dysregulated metabolites in diabetes mellitus (DM) patients. Thirty-two non-DM subjects and 32 DM patients were enrolled, and 2 significant metabolites were found in both PLS and DBS samples. In summary, detailed correlation information between PLS and DBS metabolites was first explored in this study, and it is anticipated that these results could facilitate future applications in DBS-based metabolomics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Simultaneous extraction of various types of biomolecule from a single sample can be beneficial for multiomics studies of unique specimens. An efficient and convenient sample preparation approach must be developed that can comprehensively isolate and extract biomolecules from one sample. TRIzol reagent is widely used in biological studies for DNA, RNA, and protein isolation. This study evaluated the feasibility of using TRIzol reagent for the simultaneous isolation of not only DNA, RNA, and proteins but also metabolites and lipids from a single sample. Through the comparison of known metabolites and lipids obtained using the conventional methanol (MeOH) and methyl-tert-butyl ether (MTBE) extraction methods, we determined the presence of metabolites and lipids in the supernatant during TRIzol sequential isolation. Finally, we performed untargeted metabolomics and lipidomics to examine metabolite and lipid alterations associated with the jhp0417 mutation in Helicobacter pylori by using the TRIzol sequential isolation protocol and MeOH and MTBE extraction methods. Metabolites and lipids with significant differences isolated using the TRIzol sequential isolation protocol were consistent with those obtained using the conventional MeOH and MTBE extraction methods. These results indicated that TRIzol reagent can be used to simultaneously isolate metabolites and lipids from a single sample. Thus, TRIzol reagent can be used in biological and clinical research, especially in multiomics studies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hsiao-Wei Liao reports financial support was provided by Ministry of Science and Technology of Taiwan. Hsiao-Wei Liao reports a relationship with Ministry of Science and Technology of Taiwan that includes: funding grants., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To present a multifaceted approach to ophthalmology undergraduate medical education and to assess the efficacy of an eye dissection laboratory in enhancing medical student learning., Design: Curriculum review, validation, and student feedback evaluations., Participants: Year 2 medical students enrolled in the University of Toronto's Doctor of Medicine Program., Methods: Student feedback evaluations were compiled from the University of Toronto undergraduate medical education student surveys before 2012-2016 and following introduction of the redesigned foundations ophthalmology curriculum at the University of Toronto (2017-2018). Students who participated in the Eye Dissection Lab as part of the newly designed curriculum completed the pre- and postsession satisfaction and overall interest in ophthalmology questionnaires and a knowledge-based test., Results: Analysis of 1640 student evaluations demonstrated an increase in ophthalmology curriculum rating following the launch of the foundations ophthalmology curriculum (p = 0.015). Among the 335 students who completed the eye dissection lab, there was a significant increase in the average scores for the satisfaction questionnaire, knowledge-based test, and level of interest in the field of ophthalmology from before and after the session, with improvements in scores noted in 91%, 42%, and 36% of the educational parameters of the participants, respectively (p < 0.001)., Conclusions: The newly designed foundations ophthalmology curriculum and the eye dissection lab at the University of Toronto serve as effective means for enhancing ophthalmology teaching in medical schools across Canada., (Copyright © 2021 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to report the clinical characteristics and long-term visual outcomes in a cohort of children with idiopathic intracranial hypertension (IIH)., Design: Retrospective, observational cohort study., Participants: Consecutive children who met the diagnostic criteria for definite IIH at a tertiary care pediatric hospital between 2009 and 2020., Methods: The charts of pediatric patients with IIH were reviewed. The main outcome measure was long-term visual impairment, with an analysis of clinical features by age and risk factors for a poor visual outcome., Results: There were 110 children (75 females) with IIH. At presentation, younger children with IIH were less likely to present with headaches (p = 0.01) and more likely to be asymptomatic (p = 0.03). There was a strong association with female sex (p < 0.001) and higher body mass index (p < 0.001) in adolescents in comparison to younger children. Of the 90 patients with long-term visual outcome data, only 8 (9%) had evidence of mild visual impairment (1 loss of visual acuity, 7 loss of visual field) with no cases of severe visual impairment. On risk factor analysis, the only variable associated with a poor visual outcome was greater severity of papilledema at diagnosis., Conclusions: In this large series of pediatric IIH, the long-term visual outcomes were favourable, with evidence of mild visual impairment in less than 10% of patients., (Copyright © 2021 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background: Angiotensin receptor blockers (ARBs) and β blockers are widely used in the treatment of Marfan syndrome to try to reduce the rate of progressive aortic root enlargement characteristic of this condition, but their separate and joint effects are uncertain. We aimed to determine these effects in a collaborative individual patient data meta-analysis of randomised trials of these treatments., Methods: In this meta-analysis, we identified relevant trials of patients with Marfan syndrome by systematically searching MEDLINE, Embase, and CENTRAL from database inception to Nov 2, 2021. Trials were eligible if they involved a randomised comparison of an ARB versus control or an ARB versus β blocker. We used individual patient data from patients with no prior aortic surgery to estimate the effects of: ARB versus control (placebo or open control); ARB versus β blocker; and indirectly, β blocker versus control. The primary endpoint was the annual rate of change of body surface area-adjusted aortic root dimension Z score, measured at the sinuses of Valsalva., Findings: We identified ten potentially eligible trials including 1836 patients from our search, from which seven trials and 1442 patients were eligible for inclusion in our main analyses. Four trials involving 676 eligible participants compared ARB with control. During a median follow-up of 3 years, allocation to ARB approximately halved the annual rate of change in the aortic root Z score (mean annual increase 0·07 [SE 0·02] ARB vs 0·13 [SE 0·02] control; absolute difference -0·07 [95% CI -0·12 to -0·01]; p=0·012). Prespecified secondary subgroup analyses showed that the effects of ARB were particularly large in those with pathogenic variants in fibrillin-1, compared with those without such variants (heterogeneity p=0·0050), and there was no evidence to suggest that the effect of ARB varied with β-blocker use (heterogeneity p=0·54). Three trials involving 766 eligible participants compared ARBs with β blockers. During a median follow-up of 3 years, the annual change in the aortic root Z score was similar in the two groups (annual increase -0·08 [SE 0·03] in ARB groups vs -0·11 [SE 0·02] in β-blocker groups; absolute difference 0·03 [95% CI -0·05 to 0·10]; p=0·48). Thus, indirectly, the difference in the annual change in the aortic root Z score between β blockers and control was -0·09 (95% CI -0·18 to 0·00; p=0·042)., Interpretation: In people with Marfan syndrome and no previous aortic surgery, ARBs reduced the rate of increase of the aortic root Z score by about one half, including among those taking a β blocker. The effects of β blockers were similar to those of ARBs. Assuming additivity, combination therapy with both ARBs and β blockers from the time of diagnosis would provide even greater reductions in the rate of aortic enlargement than either treatment alone, which, if maintained over a number of years, would be expected to lead to a delay in the need for aortic surgery., Funding: Marfan Foundation, the Oxford British Heart Foundation Centre for Research Excellence, and the UK Medical Research Council., Competing Interests: Declaration of interests AP has received grants paid to his institutions from the Marfan Foundation, the British Heart Foundation, the UK National Institute for Health and Care Research Biomedical Research Centre, the Gibson fund, Oxford University Hospitals Charitable Fund, and the Academy of Medical Sciences Clinical Lecturer Starter Grant scheme (which is administered by the Academy on behalf of the Academy, the Wellcome Trust, the UK Medical Research Council [MRC], the British Heart Foundation, Arthritis Research UK, Prostate Cancer UK, and the Royal College of Physicians). CR has received institutional grants from the British Heart Foundation and UK MRC. CBa has received institutional grants from the British Heart Foundation, UK MRC, NIHR, and Boehringer Ingelheim (EMPA-KIDNEY trial)., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The use of monoclonal antibody (mAb) therapeutics is increasing rapidly, but mAb concentrations vary widely between individuals and might subsequently affect mAb exposure and treatment response. Precision medicine has gained much attention in recent years, but little is known about the personalized dosage of mAb therapeutics. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been demonstrated as a selective and sensitive approach to quantify mAb therapeutics in biological samples, but current methods to quantify mAbs are usually time-consuming and require tedious sample preparation. This study developed an efficient LC-MS/MS method using an on-bead trypsin digestion procedure at a higher digestion temperature. Five mAbs, bevacizumab, evolocumab, nivolumab, pembrolizumab, and trastuzumab, used for treating different diseases, were selected for method development. Tocilizumab was selected as the internal standard. The result of the on-bead digestion protocol was compared to the conventional low-pH elution method, and it showed better sensitivity and reproducibility for most mAbs. The optimized on-bead digestion protocol used 75 μL of digestion buffer at 60 °C for a 60 min digestion. The calibration curve was generated from 10 to 200 μg mL -1 . The accuracies at the three QC levels of the 5 mAbs were all within 94.5 ± 5.2% to 111.6 ± 3.7%. The repeatability and intermediate precision of the 5 mAbs were all lower than 6.1 and 9.5% RSD, respectively. The newly developed method was successfully applied to quantify trastuzumab in six breast cancer patients under different treatment cycles, and the concentrations ranged from 66.4 to 173.2 μg mL -1 . In conclusion, the developed method is more efficient and more practical for real-world analysis of a large number of clinical samples, it could be used for routine therapeutic drug monitoring, and it could contribute to personalized mAb treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Recently, monoclonal antibody (mAb) therapy has gained increasing attention in the medical field due to its high specificity. Dried blood spots (DBSs) have been used in various clinical fields due to their unique characteristics, such as easy transportation, low invasiveness, and home sampling. However, hematocrit (HCT)-associated issues may lead to inaccurate quantification; moreover, the HCT value is required for converting the drug concentration from DBS to plasma. To simultaneously measure HCT levels and quantify mAb concentrations in DBS samples, this study used volumetrically applied 15 μL DBS, and combined protein G purification and ethanol precipitation approaches as the sample preparation method. Sixty-two clinical samples were used to investigate the HCT estimation ability by using hemoglobin (Hb) peptides. Four mAbs, bevacizumab, trastuzumab, nivolumab and tocilizumab, were selected to demonstrate our method, and pembrolizumab was used as the internal standard. The optimized method could measure four mAbs and Hb peptides simultaneously within 11 min. Moreover, a correlation study revealed that the correlation coefficient for the Hb peptides and the HCT value was larger than 0.9. The HCT estimation results revealed that for over 90% of the real DBS samples the HCT could be obtained within ±20% estimation error acceptance criteria. The method was validated in terms of accuracy and precision for the four mAbs. The developed method was further applied to simultaneously quantify mAb concentrations and estimate HCT values in six patient DBS samples to demonstrate its clinical applicability. It is believed that this newly developed method could facilitate various clinical studies and provide benefits for mAb therapies in clinical fields., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Post-stroke seizure (PSS) can have a strong negative impact on functional recovery after stroke. Researchers have identified numerous risk factors of PSS; however, the relationship between infarction location and PSS remains unclear. We recruited patients who presented with an acute cerebral infarction between 2012 and 2017 and suffered from seizures within 1 year after stroke (PSS group). PSS group was subgrouped into early-PSS and late-PSS groups based on the interval between seizure and stroke. We also recruited an equal number of acute cerebral infarction patients without post-stroke seizures during the follow-up period (Non-PSS group). All brain MRIs from the two groups were processed, whereupon normalized infarct maps from the PSS and Non-PSS groups were compared via voxel- and volumetric-based analyses. A total of 132 subjects were enrolled in the study, including PSS (n = 66, consisting of 31 early-PSS and 35 late-PSS) and Non-PSS (n = 66) patients. No significant differences were observed between the two groups in terms of stroke lateralization or severity. Image analysis revealed that the volume of infarction was larger in the PSS group than in the Non-PSS group; however, the difference did not reach the level of significance. Unlike the Non-PSS group, the PSS group presented hot spots over the left central region, left superior parietal lobule, and right frontal operculum. We observed differences between the distribution of hot spots among patients with early-PSS and those with late-PSS. We found that some brain regions were significantly associated with the development of PSS after ischemic stroke, and these regions differed between cases of early and late PSS. It appears that the location of infarction could help clinicians assess the risk of PSS in specific post-stroke stages., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to test the diagnostic accuracy of optical coherence tomography (OCT) in differentiating optic disc drusen (ODD) from papilledema in children., Design: Retrospective cross-sectional study at a tertiary-care pediatric hospital., Participants: Children with high-quality OCT imaging of ODD or papilledema., Methods: Quantitative OCT parameters and qualitative OCT features were compared for diagnostic accuracy., Results: There were 41 eyes with ODD and 21 eyes with papilledema. Both the quantitative and qualitative OCT parameters showed highly statistically significant differences between ODD and papilledema (p ≤ 0.01 for all). For quantitative parameters (Bruch's membrane opening and retinal nerve fiber layer thicknesses), the area under the curve from the receiver operator curves ranged from 0.81 to 0.90. For qualitative parameters, the sensitivity for ODD ranged from 27% to 100% and specificity ranged from 67% to 100%. The presence of at least 1 of 3 qualitative OCT parameters (hyporeflective boot-shaped area, isolated/clustered hyperreflective bands, or signal-poor regions in the core) had a sensitivity of 90% and a specificity of 100% for ODD., Conclusions: Both quantitative and qualitative OCT parameters differed significantly between ODD and papilledema in this cohort of children. A combination of several qualitative OCT features had high sensitivity for ODD while effectively ruling out papilledema., (Copyright © 2020 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Objective: Fatigue, a painful and unpleasant subjective experience, is common in perimenopausal women. Therefore, an effective tool to evaluate the fatigue-precipitating factor is important for perimenopausal women prone to fatigue syndrome., Materials and Methods: This study was surveyed by short-term perimenopausal fatigue scale. The enrollment period was from November 2019 to January 2020. The subjects were perimenopausal women prone to perimenopausal fatigue. The differences between the fatigue-precipitating factors and the degrees of fatigue and disturbance were determined by one-way ANOVA and t test., Results: A total of 220 perimenopausal women with mean age of 51.3 years were included. Among these, 64.1% did not have a habit of regular exercise and 55.5% had chronic diseases. Fatigue syndrome was found in 64.1% of subjects, who were mainly presented by shoulder and neck pain and sleep problems. There were significant differences between "perimenopausal fatigue" and "duration" (p < 0.001); "with and without regular exercise" (p = 0.05); and "with and without chronic diseases" (p = 0.03)., Conclusions: Our study showed the perimenopausal fatigue syndrome is more frequently found in perimenopausal women who have a co-morbidity (chronic illness) and do not have a habit of regular exercise. An early identification and prompt intervention may help perimenopausal women to deal with their fatigue syndrome. The short questionnaire perimenopausal fatigue scale seems to be useful for screening perimenopausal women prone to fatigue syndrome., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021. Published by Elsevier B.V.)

Recently, there has been significant interest in the influences of the human gut microbiota on many diseases, such as cardiovascular disease (CVD) and metabolic disorders. Trimethylamine N-oxide (TMAO) is one of the most frequently discussed gut-derived metabolites. Dried blood spot (DBS) sampling has been regarded as an attractive alternative sampling strategy for clinical studies and offers many advantages. For DBS sample processing, whole-spot analysis could minimize hematocrit-related bias, but it requires blood volume calibration. This study developed a method combining matrix-induced ion suppression (MIIS) with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) to estimate blood volume and quantify TMAO and its precursors and derivatives, including choline, carnitine and acetylcarnitine, in DBSs. The MIIS method used an ion suppression indicator (ISI) to measure the extent of ion suppression caused by the blood matrix, which was related to the blood volume. The results showed that the volume estimation accuracy of the MIIS method was within 91.7-109.7%. The combined MIIS and LC-MS/MS method for quantifying TMAO, choline, carnitine and acetylcarnitine was validated in terms of linearity, precision and accuracy. The quantification accuracy was within 91.2-113.2% (with LLOQ <119%), and the imprecision was below 8.0% for all analytes. A stability study showed that the analytes in DBSs were stable at all evaluated temperatures for at least 30 days. The validated method was applied to quantify DBS samples (n = 56). Successful application of the new method demonstrated the potential of this method for real-world DBS samples and to facilitate our understanding of the gut microbiota in human health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Menopause is the transitional period of women transforming from middle age to old age, and often associated with obesity. Adequate weight control (ideal body weight maintenance) is an important issue for women's health. However, little is known about the experience of Taiwanese women participating in weight management programs., Materials and Methods: The current weight management program referred to the participation and completion of a 10 h weight management program (the course of 5 weeks, 2 h per week) at a community hospital in 2016 entrusted by the government in Taiwan. Using the descriptive phenomenological research method, purposive sampling, and a semi-structured interview guide, to conduct one-on-one in-depth interviews with menopausal women, did analyses., Results: Between August and September 2016, there were 71 subjects entering into the current study, with a median age of 56 (51-60) years. The median weight reduction was 0.6 kg at the end of the course but all were satisfied with it. There were four experiences detectable in the current study, including initial benefits from weight management programs, the difficulty in facing changes, adjustments, and a better body image., Conclusions: Belief (for better health and body figure) and assistance (for change) were important issues in weight management programs, which can be used as reference for future designs of weight management program in overweight/obese menopausal women., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2020. Published by Elsevier B.V.)

Objective: To report visual outcomes for children with Coats' disease after treatment., Design: Retrospective case series., Participants: Pediatric patients with Coats' disease treated between 2000 and 2018 at a tertiary care pediatric hospital., Methods: Review of medical records. The primary outcome was visual acuity at final follow-up. Anatomical outcomes, retreatment, and risk factors for a poor outcome were also assessed., Results: There were 30 patients with Coats' disease. All cases were unilateral, and 28 (93%) were male. At presentation, 14 (47%) had stage 2 disease (retinal exudates) and 16 (53%) had stage 3 disease (subtotal or total exudative retinal detachment). All patients underwent laser photocoagulation and (or) cryopexy as primary treatment, combined with antivascular endothelial growth factor injection in 7 patients, posterior sclerotomy in 5 patients, and pars plana vitrectomy in 1 patient. Retreatment was required in 16 (53%) patients. After a median follow-up of 3.8 years, visual acuity was 20/50 or better in 6 patients (20%), 20/60 to 20/150 in 3 (10%), 20/200 to counting fingers in 8 (23%), and hand motion or worse in 14 (47%). Greater severity of disease at presentation was significantly associated with a poor visual outcome (p = 0.0001). In terms of complications, 7 (23%) eyes developed cataracts and 2 (7%) progressed to phthisis bulbi, but no patients required enucleation., Conclusions: The visual prognosis for children with Coats' disease remains poor, particularly in patients with more severe disease at presentation. The risk of severe complications and enucleation is low after treatment., (Copyright © 2019 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Monoclonal antibody (mAb) drugs have generated much interest in recent years for treating various diseases. Immunoglobulin G (IgG) represents a high percentage of mAb drugs that have been approved by the Food and Drug Administration (FDA). To facilitate therapeutic drug monitoring and pharmacokinetic/pharmacodynamic studies, we developed a general liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify the concentration of IgG-based mAbs in human plasma. Three IgG-based drugs (bevacizumab, nivolumab and pembrolizumab) were selected to demonstrate our method. Protein G beads were used for sample pretreatment due to their universal ability to trap IgG-based drugs. Surrogate peptides that were obtained after trypsin digestion were quantified by using LC-MS/MS. To calibrate sample preparation errors and matrix effects that occur during LC-MS/MS analysis, we used two internal standards (IS) method that include the IgG-based drug-IS tocilizumab and post-column infused IS. Using two internal standards was found to effectively improve quantification accuracy, which was within 15% for all mAb drugs that were tested at three different concentrations. This general method was validated in term of its precision, accuracy, linearity and sensitivity for 3 demonstration mAb drugs. The successful application of the method to clinical samples demonstrated its' applicability in clinical analysis. It is anticipated that this general method could be applied to other mAb-based drugs for use in precision medicine and clinical studies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Targeted metabolomic analysis of fatty acids has linked the dysregulation of fatty acids to many diseases. This study selected five frequently used fatty acid derivatization methods for comparison., Methods: We compared the method precisions and derivatization efficiencies, the most economical and best performing method was subjected to method validation. Twenty-four fatty acid standards were used to validate the method, which was later applied to the investigation of potential fatty acid markers of breast cancer., Results: The acetyl chloride method was demonstrated to provide the best derivatization efficiency and lowest cost for plasma samples. The ionic liquid column successfully separated positional and geometric fatty acid isomers within 26 min under the optimized conditions. Intra-day and inter-day CVs for most of the fatty acids were <10%. Over 90% of the results showed recoveries within 85%-115%. The validated method was applied to investigate potential fatty acid markers of breast cancer. The fatty acid profiling results revealed that 3 fatty acids (C22:0, C24:0, C18:2n6) were significantly lower in both pre- and post-menopausal breast cancer patients (P<0.05)., Conclusions: We demonstrated that the proposed method is an accurate, efficient and economical method for plasma metabolomic studies of fatty acids., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To investigate the impact of a graphical timeline summarizing bilateral retinoblastoma disease and treatment outcomes on parents' understanding of complex medical information., Design: Cross-sectional survey., Participants: Parents of children with retinoblastoma who were being actively managed at The Hospital for Sick Children were recruited. Forty-five parents from 42 families participated., Methods: After a standardized presentation on retinoblastoma and visual tool named Disease-Specific electronic Patient Illustrated Clinical Timeline (DePICT), parents completed a 19-item questionnaire designed to assess their understanding of treatment choices for 2 eyes in bilateral retinoblastoma as communicated using DePICT. SPSS was used to perform statistical analysis., Results: Forty-five parents from 42 families participated (65% female). Median age of participants was 34 years. Median level of participant education was completion of college/trade school. The median level of annual income was $40,000 to $70,000 CDN. Median time since diagnosis of retinoblastoma in their child was 13.5 months. Twenty-three (51%) participants were parents of children with unilateral retinoblastoma, and 22 (49%) were parents of children with bilateral retinoblastoma. Median number of correct answers was 15 of 19, and mean score was 77%. Normal distribution of scores was noted. English as a first language was significantly associated with score (p = 0.01). No significant association was observed between other variables and score in all analyses., Conclusions: This study builds on the validation of DePICT by demonstrating that parents can achieve good comprehension even when considering choices for treatment for 2 eyes with bilateral retinoblastoma. Clinical application of this tool can enhance the consent process., (Copyright © 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background: As fatty acids play an important role in biological regulation, the profiling of fatty acid expression has been used to discover various disease markers and to understand disease mechanisms. This study developed an effective and accurate comparative fatty acid analysis method using differential labeling to speed up the metabolic profiling of fatty acids., Methods: Fatty acids were derivatized with unlabeled (D0) or deuterated (D3) methanol, followed by GC-MS analysis. The comparative fatty acid analysis method was validated using a series of samples with different ratios of D0/D3-labeled fatty acid standards and with mouse liver extracts., Results: Using a lipopolysaccharide (LPS)-treated mouse model, we found that the fatty acid profiles after LPS treatment were similar between the conventional single-sample analysis approach and the proposed comparative approach, with a Pearson's correlation coefficient of approximately 0.96. We applied the comparative method to investigate voriconazole-induced hepatotoxicity and revealed the toxicity mechanism as well as the potential of using fatty acids as toxicity markers., Conclusions: In conclusion, the comparative fatty acid profiling technique was determined to be fast and accurate and allowed the discovery of potential fatty acid biomarkers in a more economical and efficient manner., (Copyright © 2014 Elsevier B.V. All rights reserved.)

As the predominant environmental biodegradation product of nonylphenol (NP) ethoxylates and with proven estrogenic effects, NP is formed during the alkylation process of phenols. The purposes of this study were (1) to examine maternal and prenatal exposure to NP in Taiwan, (2) to determine the level of placental protection against NP exposure as well as the level of NP in breast milk, and (3) to assess the potential risk for breastfed newborns exposed to NP through the milk. Thirty pairs of maternal and fetal blood samples, placenta, and breast milk during the 1st and the 3rd months of lactation were collected. External NP exposures of these specimens were then analyzed by using high-performance liquid chromatography coupling with fluorescence detection. Next, the socio-demographics, lifestyle, delivery method, dietary and work history were collected using a questionnaire. In addition, the daily intake of NP from consuming breast milk in the 1st and 3rd months for newborns was studied through deterministic and probabilistic risk assessment methods. The geometric means and geometric standard deviation of NP levels in maternal blood, fetal cord blood, placenta, and breast milk in the 1st and 3rd months were 14.6 (1.7) ng/ml, 18.8 (1.8) ng/ml, 19.8 (1.9) ng/g, 23.5 (3.2) ng/ml, and 57.3 (1.4) ng/ml, respectively. The probabilistic percentiles (50th, 75th, and 95th) of daily intake NP in breast milk were 4.33, 7.79, and 18.39 μg/kg-bw/day in the 1st month, respectively, and were 8.11, 10.78, 16.08 μg/kg-bw/day in the 3rd month, respectively. The probabilistic distributions (5th, 25th, and 50th) of risk for infants aged 1 month old were 0.27, 0.64, and 1.15, respectively, and that for infants aged 3 month old were 0.31, 0.46, and 0.62, respectively. Through repeated exposure from the dietary intake of expectant mothers, fetuses could encounter a high NP exposure level due to transplacental absorption, partitioning between the maternal and fetal compartments. Daily NP intake via breast milk in three month-old babies exceeded the tolerable daily intake (TDI) of 5 µg/kg bw/day indicated a potential risk for Taiwan infants., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Microvolt T wave alternans (MTWA) is an indicator of repolarization heterogeneity and a predictor of ventricular arrhythmia in adults with ischemic or dilated cardiomyopathy. Its implication in patients with repaired tetralogy of Fallot (TOF) is still unclear. This study sought to define the changes and the clinical implication of MTWA in these patients., Methods: Treadmill examination with modified moving average beat analysis (MMA) for MTWA was performed in 101 repaired TOF patients (60.4% male). Data from 103 age- and sex-matched subjects with normal hearts served as controls., Results: The age at latest follow-up was 20.0 ± 10.6 years. Total repair (60.4% received a transannular right ventricular outflow patch) was performed at a mean age of 4.8(± 5.8) years. After excluding 11 patients with indeterminate data, the MTWA data in 90 TOF patients revealed higher values than those in the control (25.1 ± 14.0 vs. 17.6 ± 9.2 μV, p<0.001). The values were best correlated to the presence of severe pulmonary regurgitation (p=0.006). Ten (9.9%) patients experienced late ventricular arrhythmic events. They tended to have higher MTWA values than those without (34.0 ± 16.5 vs. 24.2 ± 13.5 and p=0.053). Although the MTWA per se would not predict the late arrhythmia events better than QRS duration alone, the positive and negative predictive values increased slightly after adding the MTWA to QRS duration., Conclusions: MTWA, as measured by MMA, increased in repaired TOF patients particularly in those with severe pulmonary regurgitation and late arrhythmia events. To predict late ventricular arrhythmia, MTWA however was not superior to QRS duration alone., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Biosludge can be reused as an adsorbent after ZnCl(2) activation, pyrolysis, washing with HCl and distilled water, and drying. But the pyrolysis exhaust of ZnCl(2) immersed sludge can be hazardous to human health and the environment. The chemical composition, including carbon, nitrogen, hydrogen, sulfur and 21 trace elements, as well as the physical characteristics, including specific surface area, pore volume, pore size distribution and pore diameter of pyrolytic residue, were investigated in this work. In addition, the components of pyrolytic exhaust including 30 VOC species and 5 odorous sulfur gases were determined to evaluate the exhaust characteristics. The results indicated that the pyrolytic temperature was higher than 500°C, the specific surface area could be over 900 m(2)/g, and the total pore volume could be up to 0.8 cm(3)/g at 600°C. Exhaust concentration fractions of VOC groups were about 65-71% oxygenated VOCs, 18-21% chlorinated VOCs, 4-6% aromatic VOCs, and 6-10% acrylonitrile and cyclohexane under the specific conditions in this study., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objectives: Uncorrected congenital heart defects (CHD) with severe pulmonary hypertension (sPH, systolic pulmonary artery>70% of systolic pressure) are usually considered inoperable. We are curious to know if some selected patients might benefit from palliative operation for those sPH with uncorrected CHD., Methods: Adults or adolescents with sPH associated with ventricular septal defect (VSD) with/without great artery anomalies were selected for pulmonary artery banding (PAB) to reduce sPH. The target pulmonary pressure was less than half of the systolic blood pressure after arch or great arteries reconstruction. Repeated catheterization was performed to evaluate the feasibility of defect closure., Results: Consecutively, 8 patients (age 26 ± 9 years) received PAB as a palliative procedure in the past 8 years without mortality. The pre-PAB systolic pulmonary pressure was 119 ± 9 mmHg. Additional PAB had been applied in 4 of them. All patients showed significant improvement in function class (III to I or II). The mean post-PAB pulmonary pressure decreased significantly (77.5 ± 9.2 mmHg to 42.0 ± 9.0 mmHg) and 6-minute walk test was also found to have great improvement (270 ± 86 m to 414 ± 49 m), but the saturation at rest did not show a difference. Three of them received corrective surgery to close defects over 3-5 years., Conclusion: For some selected adult sPH with uncorrected CHD, PAB can work as a palliative procedure to improve their functional class and even provide a chance of total repair., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Introduction: The provision of optimal care for women with gynaecologic cancer may be threatened due to the changing demographics of patients and the projected increasing shortage of gynaecologic oncologists in Canada. We evaluated the career plans of Canadian residents in obstetrics and gynaecology to determine the proportion of residents currently considering a career in gynaecologic oncology (GO) and to explore factors that may affect their career decisions., Methods: Following institutional ethics approval, all residents at 13 participating Canadian obstetrics and gynaecology residency training programs were contacted by email to complete a 20-item confidential questionnaire examining career plans. Quantitative data were analyzed using SAS v9.1. Qualitative data were coded by theme and grouped into various domains., Results: Of 293 residents, 105 (36%) participated. More than half of these were considering at least one obstetrics and gynaecology subspecialty, but 53% indicated that their most appealing career path was general obstetrics and gynaecology. Although 50% of residents had ever considered a career in GO, only 17% were considering a GO career at the time of the survey. When rated as positive influences, medical school exposure, resident exposure, role models within GO, colleagues, other health care professionals, "my individual life circumstances," "my personal attributes," the clinical, research, and educational components of GO, the GO patient population, and relation with gynaecologic oncologists and other specialists were significant predictors of current GO interest. Themes that emerged from qualitative analysis revealed that the clinical, professional, and research domains were predominant influences among residents currently considering a career in GO., Conclusions: GO is an infrequent career choice for Canadian residents in obstetrics and gynaecology, and a number of factors significantly affect GO career decisions. Modifying factors such as educational experiences, work environment, and current practice models may lead to improved recruitment to the subspecialty, which is crucial for meeting the future needs of women with gynaecologic malignancies in Canada.

Marfan syndrome has been associated with approximately 562 mutations in the fibrillin-1 (FBN1) gene. Mutation scanning of the FBN1 gene with DNA direct sequencing is time-consuming and expensive because of its large size. This study analyzed the diagnostic value of high-resolution melting analysis as an alternative method for scanning of the FBN1 gene. A total of 75 polymerase chain reaction (PCR) amplicons (179-301bp, average 256bp) that covered the complete coding regions and splicing sites were evaluated on the 96-well LightCycler system. Melting curves were analyzed as fluorescence derivative plots (-dF/dT vs. temperature). To determine the sensitivity of this method, a total of 82 samples from patients with Marfan syndrome and 50 unaffected individuals were analyzed. All mutations reported in this study had been confirmed previously by direct sequencing analysis. Melting analysis identified 48 heterozygous variants. The variant c.3093 G>T (exon 25) was incorrectly identified by melting curve analysis. The sensitivity of the technique in this sample was 98.78% (81/82). This study demonstrated that high-resolution melting analysis is a reliable gene scanning method with greater speed than DNA sequencing. Our results support the use of this technology as an alternative method for the diagnosis of Marfan syndrome as well as its suitability for high-throughput mutation scanning of other large genes.

Natural products are normally obtained by organic solvent extraction and many subsequent chromatographic separations. Compounds of interest are often isolated with very low yield and limited purity. An aqueous two-phase extraction process combined with a simple ethanol treatment, for removing excess inorganic salt, has been developed for preparation of geniposide from gardenia. The system was comprised of PE62, a random copolymer composed of 20% ethylene oxide and 80% propylene oxide, KH2PO4 and ethanol. To find optimal conditions, the partition behavior of geniposide under an aqueous two-phase system was investigated. Various factors were considered, including the concentration of salt, the concentration of polymer, the sample loading, and the addition of ethanol. The experimental results demonstrated that increasing salt concentration or decreasing PE62 concentration results in enhancement of the geniposide partition in the salt-rich phase. The addition of ethanol and higher sample loading also promoted the partition efficiency of geniposide. Based on this study, an optimized system containing 5% PE62, 7.5% KH2PO4, and 10% ethanol was tested on a large-scale extraction. A 39.0-g aliquot of final product (in powder form) with 77% purity of geniposide can be effectively extracted from 500 g of gardenia fruit. This process is proved to be useful for industrial application of geniposide preparation.