Developments in understanding and applying prebiotics in research and practice-an ISAPP conference paper.

AIMS: The concept of using specific dietary components to selectively modulate the gut microbiota to confer a health benefit, defined as prebiotics, originated in 1995. In 2018, a group of scientists met at the International Scientific Association for Probiotics and Prebiotics annual meeting in Singapore to discuss advances in the prebiotic field, focussing on issues affecting functionality, research methodology and geographical differences. METHODS AND RESULTS: The discussion ranged from examining scientific literature supporting the efficacy of established prebiotics, to the prospects for establishing health benefits associated with novel compounds, isolated from different sources. CONCLUSIONS: While many promising candidate prebiotics from across the globe have been highlighted in preliminary research, there are a limited number with both demonstrated mechanism of action and defined health benefits as required to meet the prebiotic definition. Prebiotics are part of a food industry with increasing market sales, yet there are great disparities in regulations in different countries. Identification and commercialization of new prebiotics with unique health benefits means that regulation must improve and remain up-to-date so as not to risk stifling research with potential health benefits for humans and other animals. SIGNIFICANCE AND IMPACT OF STUDY: This summary of the workshop discussions indicates potential avenues for expanding the range of prebiotic substrates, delivery methods to enhance health benefits for the end consumer and guidance to better elucidate their activities in human studies.

Current development in non-enzymatic lipid peroxidation products, isoprostanoids and isofuranoids, in novel biological samples.

Isoprostanoids and isofuranoids are lipid mediators that can be formed from omega-3 and omega-6 polyunsaturated fatty acids (PUFAs). F2-isoprostanes formed from arachidonic acid, especially 15-F2t-isoprostane, are commonly measured in biological tissues for decades as the biomarker for oxidative stress and diseases. Recently, other forms of isoprostanoids derived from adrenic, eicosapentaenoic, and docosahexaenoic acids namely F2-dihomo-isoprostanes, F3-isoprostanes, and F4-neuroprostanes respectively, and isofuranoids including isofurans, dihomo-isofurans, and neurofurans are reported as oxidative damage markers for different metabolisms. The most widely used samples in measuring lipid peroxidation products include but not limited to the blood and urine; other biological fluids, specialized tissues, and cells can also be determined. In this review, measurement of isoprostanoids and isofuranoids in novel biological samples by gas chromatography (GC)-mass spectrometry (MS), GC-MS/MS, liquid chromatography (LC)-MS, and LC-MS/MS will be discussed.

Synthesis and discovery of phytofurans: metabolites of α-linolenic acid peroxidation.

Phytofurans are novel metabolites produced by non-enzymatic peroxidation of α-linolenic acid. An unprecedented Payne rearrangement-cyclization of a C2-symmetric bis-epoxide permitted construction of the core 3-hydroxy-2,5-disubstituted tetrahydrofuran. LC-MS/MS investigation provided evidence for the presence of phytofurans in nuts and seeds for the first time.

Special Issue on "Analytical Methods for Oxidized Biomolecules and Antioxidants" The use of isoprostanoids as biomarkers of oxidative damage, and their role in human dietary intervention studies.

Isoprostanoids are a group of non-enzymatic oxidized lipids from polyunsaturated fatty acids. They are commonly used as biomarkers for oxidative damage, to assess in vivo lipid peroxidation in diseases related to the vascular system and neurodegeneration. Currently, there is a mismatch with the outcome in the use of these biomarkers in intervention studies, particularly when testing the effect of antioxidants such as vitamins C and E, or zinc, or a cocktail of these, with other food components. Much of this is because the biomarkers, the method of measurement, and the duration of supplementation are unsuitable. In this review, we will highlight the formation of isoprostanoids from their respective fatty acids, and their application as biomarkers for oxidative damage in vivo, considering human dietary intervention studies evaluating plasma and urine, using mass spectrometry techniques.

Prenatal exposure to the contaminant perfluorooctane sulfonate elevates lipid peroxidation during mouse fetal development but not in the pregnant dam.

Perfluorooctane sulfonate (PFOS), a member of the perfluorinated chemical family, has been convincingly demonstrated to affect lipid metabolism in animals and humans and readily crosses the placenta to exert its effects on the developing fetuses. While its exact mechanism is still not clear, PFOS exposure has long been suggested to exert its toxicity via oxidative stress and/or altered gene expression. Levels of PFOS and malondialdehyde in various organs and cell cultures have been widely determined as general indicators of non-specific lipid peroxidation after PFOS exposure. In this study, the oxidation of precise polyunsaturated fatty acids and their metabolites, derived from enzymatic and non-enzymatic pathways was determined following PFOS exposure in both adult and maternal/fetal mice. CD-1 mice were exposed to 3 mg/kg body weight/day of PFOS in corn oil by oral gavage until late gestation (GD17). We demonstrated that lipid peroxidation was particularly and exclusively affected in fetuses exposed to PFOS, but this was not the case in the maternal mice, where limited effects were observed in the enzymatic oxidation pathway. In this study, we demonstrated that PFOS-induced lipid peroxidation might have a greater impact in free radical generation in fetuses than in dams and could be responsible for affecting fetal development. In addition, antioxidant enzymes, such as superoxide dismutase and catalase, appeared to maintain oxidative stress homeostasis partially in adult mice exposed to PFOS. Taken together, our results might elucidate the mechanism of how PFOS induces oxidative stress in vivo.

Hong Kong Chinese teachers' attitudes towards life-sustaining treatment in the dying patients.

OBJECTIVE: To evaluate the attitudes of Hong Kong Chinese teachers towards life-sustaining treatment in the dying patients. DESIGN: Prospective structured questionnaire survey. SETTING: Hong Kong Institute of Education. SUBJECTS AND METHODS: All teaching staff at the Hong Kong Institute of Education were sent the survey questionnaire. The questionnaire gathered demographic data, information on experience of 'life and death' decision-making, and views on life-sustaining treatment decisions. Respondents were also requested to respond to statements on life-sustaining treatment using a 5-point Likert Scale (1 representing strong disagreement and 5 representing strong agreement). RESULTS: A total of 436 questionnaires were sent to teaching staff at the Hong Kong Institute of Education. The response rate was 27.8%. More than half (65.8%) of the respondents were aged between 30 and 49 years. There was an equal proportion of men and women among respondents. The respondents agreed with statements supporting end-of-life decisions (mean aggregate score, 3.13; standard deviation, 1.24; P<0.0001), and disagreed with statements against such decisions (mean aggregate score, 2.81; standard deviation, 1.22; P<0.0001). If the patient is competent, half of the respondents agreed that the patient alone should make the decision, while 27.2% believed that it should be a joint decision made by the patient, the family, and the doctor. Conversely, if the patient is incompetent, 52.6% agreed that it should be a joint decision made by the family and the doctor. There was strong support for advanced directives, whereby decisions in relation to life-sustaining treatment were legally recorded in advance (mean score, 3.62; P=0.0001). CONCLUSION: The teachers in this survey appear to support the practice of withdrawing and withholding life-sustaining treatment in the dying patients when medical treatment is considered futile. Although patient autonomy in decision-making was supported by the greatest number of respondents, joint decision-making by the patient, family members, and doctors was also favoured by a substantial group. There was strong support for the use of advanced directives with respect to life-sustaining treatment.

Thyroid surgery--the Tan Tock Seng Hospital otolaryngology experience.

INTRODUCTION: Central to the management of a patient with a thyroid nodule is the evaluation of the risk of malignancy. Postoperative morbidity, though rare, remains a concern because of its impact on the quality of the life of the patient. MATERIALS AND METHODS: A retrospective audit of 91 consecutive patients who underwent thyroid surgery for thyroid nodules, at the Department of Otolaryngology, Tan Tock Seng Hospital, between January 1995 and December 2000. RESULTS: The sensitivity and specificity of fine-needle aspiration cytology (FNAC) were 60% and 100%, respectively. The sensitivity and specificity of intraoperative frozen section examination was 82% and 100%, respectively. Sixty-four patients experienced no postoperative morbidity. Of the 27 patients with postoperative morbidity, only 1 was permanent. The incidence of transient and permanent biochemical hypocalcaemia was 44% and 0%, respectively. Nodal dissection performed together with total thyroidectomy increased the incidence of postoperative hypocalcaemia (P < 0.05). The number of parathyroid glands preserved in situ did not predict for postoperative hypocalcaemia. The incidence of transient and permanent recurrent laryngeal nerve (RLN) palsy was 10.3% and 1.1% (8.2% and 0.9% of nerves at risk), respectively. Tracheo-oesophageal groove clearance performed together with thyroid lobectomy did not increase the incidence of postoperative RLN palsy (P > 0.05). The median hospital stay was 3 days for benign thyroid disease, 4.5 and 16 days for malignant disease with tracheo-oesophageal groove clearance only and with neck dissection, respectively. CONCLUSION: The combination of clinical examination and FNAC remains the mainstay in selecting patients for surgery. Frozen section examination is an important intraoperative diagnostic adjunct to decide the extent of surgery. With proper surgical training and experience, thyroid surgery for malignancy can be undertaken with minimum postoperative morbidity and a short hospital stay.

Central nervous system inflammatory demyelinating disorders among Hong Kong Chinese.

Classical multiple sclerosis (CMS) and neuromyelitis optica spectrum disorders (NMOSD) are distinct central nervous system inflammatory demyelinating disorders (CNS IDD). Early diagnosis of CNS IDD is important as appropriate immunotherapies to optimize prognosis. We studied the diagnoses of CNS IDD among Hong Kong Chinese in a hospital-based setting. Consecutive Chinese patients who presented to our hospital with clinically isolated syndrome and subsequently diagnosed to have CNS IDD from 1980 to 2010 were reviewed. Patients with known diagnosis of CNS IDD referred for further care were excluded. Serial sera were assayed for aquaporin-4 autoantibodies (AQP4 Ab), at least 3 assays within 2-5years. A total of 210 patients diagnosed to have CNS IDD with disease duration of at least 2years were studied. Among 198 patients with serial sera available, 40 (20.2%, 20 had NMO and 20 other NMOSD) were AQP4 Ab-positive. Four patients who were AQP4 Ab-negative on the initial assay converted to AQP4 Ab-positive on repeated assays. The diagnoses of 210 patients were CMS in 88 (41.9%), NMOSD 47 (22.4%, 27 NMO, 20 other NMOSD), single attack of myelitis 23 (11.0%), single attack of optic neuritis 21 (10.0%), relapsing myelitis 10 (4.8%), acute disseminated encephalomyelitis (ADEM) 9 (4.3%), relapsing optic neuritis in 6 (2.9%), opticospinal multiple sclerosis 3 (1.4%) and single attack of brainstem encephalitis 3 (1.4%). Compared to CMS, NMOSD patients had older onset age, lower frequencies of brain MRI abnormalities and CSF OCB, higher frequency of LETM, higher CNS inflammation attack frequency in the first 2years, worse clinical outcome with higher EDSS score and mortality rate. This hospital-based study suggests that CMS (41.9%) and NMOSD (22.4%) are the most common CNS IDD among Hong Kong Chinese. NMOSD has worse clinical outcome than CMS. Detection of AQP4 Ab facilitates early diagnosis and prompts immunotherapies of NMOSD.

Oculomotor nerve palsy after functional endoscopic sinus surgery.

We report an unusual case of partial oculomotor nerve palsy occurring after functional endoscopic sinus surgery, without anatomical disruption of the extra-ocular muscles. The clinical course and possible pathogenic mechanisms are also presented.

Why generic and disease-specific quality-of-life instruments should be used together for the evaluation of patients with persistent allergic rhinitis.

BACKGROUND: The importance of assessing health-related quality of life (HRQL) of patients with allergic rhinitis (AR) has been well established, but the specific roles of rhinitis-specific or general health instruments have not been delineated. OBJECTIVE: We analysed the psychometric properties of a disease-specific instrument, the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ) and the general health instrument, the Medical Outcome Short-Form 36 (SF-36) as they are employed in combination in patients with persistent AR in clinical practice. METHOD: We analysed the data collected from a prospective study of 43 newly diagnosed patients with persistent AR and 44 controls. We interviewed the patients four times, at baseline, weeks 4, 8 and 10. RESULTS: The RQLQ and SF-36 have good discriminative property, internal consistency, and test-retest reliability. The RQLQ is superior to the SF-36 as an evaluative instrument because more of its domains respond to change, the magnitude of change was greater, and the response was faster. The SF-36 is more susceptible to floor and ceiling effects. Both instruments are unsuitable for mildly symptomatic patients based on Rasch model analysis. Each questionnaire assesses a distinct and significant portion of the total HRQL of persistent AR. CONCLUSION: The SF-36 and RQLQ are good for discriminating rhinitis patients from controls, but the former is poor for detecting changes in QOL. Both are inappropriate for mildly symptomatic patients. Each instrument measures non-overlapping halves of the measurable HRQL. For an assessment of the HRQL in persistent AR that is complete and responsive both instruments should be employed together.