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Botulinum Neurotoxin A (BoNT/A) is a bacterial protein that has proven to be a valuable pharmaceutical in therapeutic indications and aesthetic medicine. One major concern is the formation of neutralizing antibodies (nAbs) to the core BoNT/A protein. These can interfere with the therapy, resulting in partial or complete antibody (Ab)-mediated secondary non-response (SNR) or immunoresistance. If titers of nAbs reach a level high enough that all injected BoNT/A molecules are neutralized, immunoresistance occurs. Studies have shown that continuation of treatment of neurology patients who had developed Ab-mediated partial SNR against complexing protein-containing (CPC-) BoNT/A was in some cases successful if patients were switched to complexing protein-free (CPF-) incobotulinumtoxinA (INCO). This seems to contradict the layperson's basic immunological understanding that repeated injection with the same antigen BoNT/A should lead to an increase in antigen-specific antibody titers. As such, we strive to explain how immunological memory works in general, and based on this, we propose a working hypothesis for this paradoxical phenomenon observed in some, but not all, neurology patients with immunoresistance. A critical factor is the presence of potentially immune-stimulatory components in CPC-BoNT/A products that can act as immunologic adjuvants and activate not only naïve, but also memory B lymphocyte responses. Furthermore, we propose that continuous injection of a BoN/TA formulation with low immunogenicity, e.g., INCO, may be a viable option for aesthetic patients with existing nAbs. These concepts are supported by a real-world case example of a patient with immunoresistance whose nAb levels declined with corresponding resumption of clinical response despite regular INCO injections.

Oral health of the older population has long been overlooked in global healthcare agenda. Limited access to oral healthcare for dependent older adults results in poor oral health, negatively impacting their quality of life, nutrition and overall well-being. Especially for nations experiencing rapid ageing population, efforts must be urgently made to integrate oral healthcare services into the current healthcare system and policy. Singapore stands out as one of the most rapidly ageing nations in Southeast Asia, achieving remarkable progress in the healthcare field, as well as advancements in social modernization and economic growth. It now faces the growing burden of the dependent older population and is required to respond to the complex challenges associated with providing holistic eldercare services and ensuring the well-being of its ageing population. This narrative review offers an overview of Singapore's current healthcare policy and system development for the older population, with a specific focus on oral healthcare. The goal is to shed light on this underexplored area, highlighting the challenges that need to be tackled to improve the accessibility of oral health services for dependent older adults., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The formation of neutralizing antibodies is a growing concern in the use of botulinum neurotoxin A (BoNT/A) as it may result in secondary treatment failure. Differences in the immunogenicity of BoNT/A formulations have been attributed to the presence of pharmacologically unnecessary bacterial components. Reportedly, the rate of antibody-mediated secondary non-response is lowest in complexing protein-free (CF) IncobotulinumtoxinA (INCO). Here, the published data and literature on the composition and properties of the three commercially available CF-BoNT/A formulations, namely, INCO, Coretox ® (CORE), and DaxibotulinumtoxinA (DAXI), are reviewed to elucidate the implications for their potential immunogenicity. While all three BoNT/A formulations are free of complexing proteins and contain the core BoNT/A molecule as the active pharmaceutical ingredient, they differ in their production protocols and excipients, which may affect their immunogenicity. INCO contains only two immunologically inconspicuous excipients, namely, human serum albumin and sucrose, and has demonstrated low immunogenicity in daily practice and clinical studies for more than ten years. DAXI contains four excipients, namely, L-histidine, trehalosedihydrate, polysorbate 20, and the highly charged RTP004 peptide, of which the latter two may increase the immunogenicity of BoNT/A by introducing neo-epitopes. In early clinical studies with DAXI, antibodies against BoNT/A and RTP004 were found at low frequencies; however, the follow-up period was critically short, with a maximum of three injections. CORE contains four excipients: L-methionine, sucrose, NaCl, and polysorbate 20. Presently, no data are available on the immunogenicity of CORE in human beings. It remains to be seen whether all three CF BoNT/A formulations demonstrate the same low immunogenicity in patients over a long period of time.

Objective: Diet significantly contributes to dental decay (caries) yet monitoring and modifying patients' diets is a challenge for many dental practitioners. While many oral health and diet-tracking mHealth apps are available, few focus on the dietary risk factors for caries. This study aims to present the development and key features of a dental-specific mobile app for diet monitoring and dietary behaviour change to prevent caries, and pilot data from initial user evaluation., Methods: A mobile app incorporating a novel photo recognition algorithm and a localised database of 208,718 images for food item identification was developed. The design and development process were iterative and incorporated several behaviour change techniques commonly used in mHealth. Pilot evaluation of app quality was assessed using the end-user version of the Mobile Application Rating Scale (uMARS)., Results: User feedback from the beta-testing of the prototype app spurred the improvement of the photo recognition algorithm and addition of more user-centric features. Other key features of the final app include real-time prompts to drive actionable behaviour change, goal setting, comprehensive oral health education modules, and visual metrics for caries-related dietary factors (sugar intake, meal frequency, etc.). The final app scored an overall mean (standard deviation) of 3.6 (0.5) out of 5 on the uMARS scale., Conclusion: We developed a novel diet-tracking mobile app tailored for oral health, addressing a gap in the mHealth landscape. Pilot user evaluations indicated good app quality, suggesting its potential as a useful clinical tool for dentists and empowering patients for self-monitoring and behavioural management., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

With increasing off-label aesthetic indications using higher botulinum neurotoxin A (BoNT-A) doses and individuals starting treatment at a younger age, particularly in Asia, there is a greater risk of developing immunoresistance to BoNT-A. This warrants more in-depth discussions by aesthetic practitioners to inform patients and guide shared decision-making. A panel comprising international experts and experienced aesthetic practitioners in Hong Kong discussed the implications and impact of immunoresistance to BoNT-A in contemporary aesthetic practice, along with practical strategies for risk management. Following discussions on a clinical case example and the results of an Asia-Pacific consumer study, the panel concurred that it is a priority to raise awareness of the possibility and long-term implications of secondary non-response due to immunoresistance to BoNT-A. Where efficacy and safety are comparable, a formulation with the lowest immunogenicity is preferred. The panel also strongly favored a thorough initial consultation to establish the patient's treatment history, explain treatment side effects, including the causes and consequences of immunoresistance, and discuss treatment goals. Patients look to aesthetic practitioners for guidance, placing an important responsibility on practitioners to adopt risk-mitigating strategies and adequately communicate important risks to patients to support informed and prudent BoNT-A treatment decisions.

Background: The likelihood of experiencing the impact of chronic disease rises with age, and cumulative functional deficits over time increase the risk of frailty in older adults. The exact causes of frailty are not clear, and research is needed to identify appropriate intervention measures to reduce risk of developing frailty in old age., Objective: To review the evidence on the relationship between frailty, dental status and chronic periodontitis and to determine if improvements in oral health of older adults can contribute to reversal of frailty., Results: The oral cavity is the entry point to the gastro-intestinal tract, and natural teeth facilitate efficient mastication of food prior to swallowing and subsequent digestion. The loss of natural teeth, which is gradual and cumulative over the life course, is associated with diminished nutritional intake, especially in older adults. Furthermore, chronic periodontitis has been postulated as a risk factor for frailty. The evidence supporting a strong relationship between oral health status and frailty is not clearcut. Cross sectional studies suggest an association with missing teeth and chronic periodontal inflammation. However, there are very few longitudinal studies and accordingly, it is not currently possible to claim a causal relationship. As yet, there is no evidence to suggest that improvements in oral health contribute to reversal of frailty., Conclusion: Longitudinal studies with robust designs are required to better inform the relationship across functional dentition, chronic periodontitis and frailty in older adults.

Background: Clinical trials in cancer frequently include cancer-specific measures of health but not preference-based measures such as the EQ-5D that are suitable for economic evaluation. Mapping functions have been developed to predict EQ-5D values from these measures, but there is considerable uncertainty about the most appropriate model to use, and many existing models are poor at predicting EQ-5D values. This study aims to investigate a range of potential models to develop mapping functions from 2 widely used cancer-specific measures (FACT-G and EORTC-QLQ-C30) and to identify the best model., Methods: Mapping models are fitted to predict EQ-5D-3L values using ordinary least squares (OLS), tobit, 2-part models, splining, and to EQ-5D item-level responses using response mapping from the FACT-G and QLQ-C30. A variety of model specifications are estimated. Model performance and predictive ability are compared. Analysis is based on 530 patients with various cancers for the FACT-G and 771 patients with multiple myeloma, breast cancer, and lung cancer for the QLQ-C30., Results: For FACT-G, OLS models most accurately predict mean EQ-5D values with the best predicting model using FACT-G items with similar results using tobit. Response mapping has low predictive ability. In contrast, for the QLQ-C30, response mapping has the most accurate predictions using QLQ-C30 dimensions. The QLQ-C30 has better predicted EQ-5D values across the range of possible values; however, few respondents in the FACT-G data set have low EQ-5D values, which reduces the accuracy at the severe end., Conclusions: OLS and tobit mapping functions perform well for both instruments. Response mapping gives the best model predictions for QLQ-C30. The generalizability of the FACT-G mapping function is limited to populations in moderate to good health., (© The Author(s) 2015.)

Introduction: Congenital atresia of the common and external iliac arteries is a rare vascular anomaly that may be associated with congenital renal or genitourinary malformations. In ESRD patients, its presence may pose potential problems during renal transplantation., Case Presentation: We report a rare case of kidney transplantation in a patient with VACTERL syndrome who was found to have absent right common and external iliac arteries during pre-operative imaging. Vascular supply to the right lower limb is derived from an anomalous branch from the left internal iliac artery which takes on a convoluted course across the pelvis. Kidney transplantation was performed successfully with implantation performed on the left side., Discussion: Isolated cases of congenital iliac artery atresia have been described in association with urological abnormalities but no clear association has yet been established. However, we feel that it may be useful to perform routine angiographic evaluation for ESRD patients with congenital genitourinary abnormalities being planned for kidney transplantation. While most cases of congenital iliac artery anomalies are symptomatic with claudication, some remain asymptomatic with normal physical examination findings. There is some evidence in literature suggesting the usefulness of routine pre-operative CT in a selective group of patients., Conclusion: Kidney transplantation in such cases is safe and we recommend routine pre-operative imaging of patients known to have congenital genitourniary abnormalities. The kidney should be implanted heterotopically to the contralateral side of the vascular anomaly and care must be taken to preserve vascular supply to the lower limbs., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Gain-of-function mutations involving c-kit protein, a cell-surface transmembrane receptor for stem cell factor, have been identified as a key oncogenic driver in a variety of solid tumours. Coupled with the development of tyrosine kinase inhibitors such as imatinib, c-kit has emerged as a viable drug target in what seems to be a validated therapeutic concept. This review will focus on gastrointestinal stromal tumours and melanomas, two types of solid tumours most closely associated with KIT gene mutations. The biology of KIT mutations in both conditions, as well as the value of KIT mutation testing in predicting disease and treatment outcomes are discussed. Since initial response to imatinib is largely influenced by mutation status, genotyping these tumours serves to facilitate personalised oncology. We also summarise our experience with diagnostic reporting of KIT mutation analysis over a period of 3 years, and briefly survey future developments in treatment, which indeed look very promising.

Introduction: We assessed the pedagogical value of a student-led community-based experiential learning project called the Public Health Screening (PHS) run by medical and nursing students of the National University of Singapore's Yong Loo Lin School of Medicine (NUS YLLSoM)., Materials and Methods: We conducted a cross-sectional study using a self-administered anonymised questionnaire on medical and nursing students who participated in PHS using the Fund for the Improvement of Postsecondary Education (FIPSE) Survey Instrument. Participants also gave an overall score for their learning experience at the PHS., Results: The participation rate was 93.1% (576/619) for medical students and 100% (37/37) for nursing students. All participants gave the PHS learning experience a high rating (median = 8 out of maximum of 10, inter-quartile range, 7 to 9). A majority of participants felt that PHS had helped them to improve across all domains surveyed. For medical students, those in preclinical years and females were independently more likely to feel that PHS had helped them to improve in communication skills, teamwork, ability to identify social issues, taking action, and gaining and applying their knowledge than those in clinical years and males. Improved ability to interact with patients (β=1.64, 95%CI, 1.01-2.27), appreciation of challenges to healthcare faced by Singaporeans from lower income groups (β=0.93, 95%CI, 0.49-1.37), thinking of others (β=0.70, 95%CI, 0.04-1.37) and tolerance of different people (β =0.63, 95%CI, 0.17-1.10) were strongly associated with the overall rating score., Conclusion: PHS was a positive learning experience in a wide range of domains for all students involved. This suggests that student-organised community-based experiential learning projects have potential educational value for both medical and nursing students.

A fiber Bragg grating (FBG) with an inverse-Gaussian apodization function is proposed and fabricated. It is shown that such a FBG possesses dual-wavelength narrow transmission peaks and the wavelength spacing between the two peaks is easily controllable during fabrication. Incorporating such a FBG filter into a fiber laser with a linear cavity, we obtain stable dual-wavelength emission with 0.146 nm wavelength spacing. This arrangement provides a simple and low cost way of achieving dual-wavelength fiber laser operation.

This work investigates the use of optical coherence tomography (OCT) to identify virus infection in orchid plants. Besides revealing the cross-sectional structure of orchid leaves, highly scattering upper leaf epidermides are detected with OCT for virus-infected plants. This distinct feature is not observable under histological examination of the leaf samples. Furthermore, the leaf epidermides of stressed but healthy plants, which exhibit similar visual symptoms as virus-infected plants, are not highly scattering and are similar to those of healthy plants. The results suggest that virus-infected orchid plants can be accurately identified by imaging the epidermal layers of their leaves with OCT. The OCT modality is suitable for fast, nondestructive diagnosis of orchid virus infection, which may potentially lead to significant cost savings and better control of the spread of viruses in the orchid industry.

This paper reports a compact and practical fluorescence sensor using an in-fiber microchannel. A blue LED, a multimode PMMA or silica fiber and a mini-PMT were used as an excitation source, a light guide and a fluorescence detector, respectively. Microfluidic channels of 100 microm width and 210 microm depth were fabricated in the optical fibers using a direct-write CO(2) laser system. The experimental results show that the sensor has high sensitivity, able to detect 0.005 microg L(-1) of fluorescein in the PBS solution, and the results are reproducible. The results also show that the silica fiber sensor has better sensitivity than that of the PMMA fiber sensor. This could be due to the fouling effect of the frosty layer formed at the microchannel made within the PMMA fiber. It is believed that this fiber sensor has the potential to be integrated into microfluidic chips for lab-on-a-chip applications.

High-strength dental stone is widely used to produce dies for the fabrication of restorations with the lost-wax technique. It is normal to wait at least 24 hours for casts to dry and gain sufficient strength prior to initiating laboratory procedures. This waiting time may be greatly reduced by using microwave drying. This study determined the optimum microwave energy density for preserving working die accuracy of a Type IV high-strength dental stone (Silky Rock; Whipmix). Cylindrical die specimens were fabricated according to manufacturer's instructions and allowed to set for one hour. The specimens were subsequently treated as follows: Group I (Control group)--air dried; Group II--microwaved at 700W for 40 seconds; Group III--microwaved at 490W for 60 seconds. The percentage weight loss of cylindrical specimens (n = 6) and the percentage dimensional change (n = 7) of die specimens in three axes (x, y and z) were determined at 30 minutes, 1 hour and 24 hours after air drying/microwaving. Weight loss was measured using an electronic digital balance, while dimensional changes were assessed using image analysis software. Data was subject to ANOVA/Scheffe's tests at significance level 0.05. No significant difference in percentage weight loss was observed between air drying for 24 hours and microwaved specimens at all time intervals. Although no significant difference in percentage dimensional changes was observed between specimens microwaved at 490W for 60 seconds and specimens air dried for 24 hours, significant changes in x, y and z dimensions were observed after microwaving at 700W for 40 seconds at various time intervals. Microwave radiation at 490W for 60 seconds is recommended for drying Type IV high-strength dental stone. Further investigations are required to determine changes in physical properties associated with the aforementioned microwave power density.