Search

This article explores the use of deep brain stimulation (DBS) as a treatment for Parkinson's disease (PD). PD is a neurodegenerative disorder with both motor and non-motor symptoms. While current therapies focus on supplementing dopamine, DBS offers an alternative approach by implanting stimulating electrodes into specific brain structures. DBS has shown promise in improving motor function and quality of life for PD patients, but its long-term benefits and effects on disease progression are still uncertain. The article also discusses the potential of adaptive DBS, which allows for real-time adjustments to stimulation parameters, to enhance motor function and reduce side effects. Further research is needed to determine the optimal timing for DBS and whether it provides any neuroprotective benefits for PD patients. [Extracted from the article]

Objectives: Hospital outbreaks of SARS-CoV-2 infection are dreaded but preventable catastrophes. We reviewthe literature to examine the pattern of SARS-CoV-2 transmission in hospitals and identify potential vulnerabilities to mitigate the risk of infection. Methods: Three electronic databases (PubMed, Embase and Scopus) were searched from inception to July 27, 2021 for publications reporting SARS-CoV-2 outbreaks in hospital. Relevant articles and grey literature reports were hand-searched. Results: Twenty-seven articles that described 35 SARS-CoV-2 outbreaks were included. Despite epidemiological investigations, the primary case could not be identified in 37% of outbreaks. Healthcare workers accounted for 40% of primary cases (doctors 17%, followed by ancillary staff 11%). Mortality among infected patients was approximately 15%. By contrast, none of the infected HCWs died. Several concerning patterns were identified, including infections involving ancillary staff and healthcare worker infections from the community and household contacts. Conclusion: Continuous efforts to train-retrain and enforce correct personal protective equipment use and regular routine screening tests (especially among ancillary staff) are necessary to stem future hospital outbreaks of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Autoimmune epilepsy is increasingly recognized as a distinct clinical entity, driven in large part by the recent discovery of neural autoantibodies in patients with isolated or predominant epilepsy presentations. Detection of neural autoantibodies in high-risk epilepsy patients supports an immune-mediated cause of seizures and, if applicable, directs the search for an underlying cancer when the paraneoplastic association of the associated antibody is compelling. Early diagnosis of autoimmune epilepsy is crucial, as prompt initiation of immunosuppressive treatment increases the likelihood of achieving either seizure freedom or a substantial reduction in seizure frequency. A practical clinical approach that incorporates risk scores to guide patient selection on the basis of clinical features, neural autoantibodies, and a treatment trial of immunotherapy is suggested. Elucidating an immunological basis of epilepsy provides neurologists with wider treatment options (incorporating immune-suppressive treatment), in addition to standard antiepileptic drugs, which often improves patient outcomes. [ABSTRACT FROM AUTHOR]

Background Leukotriene B4, a 5-lipoxygenase product of arachidonic acid with potent chemotactic effects on neutrophils, has not been assessed in dengue patients. In this study, plasma leukotriene B4 and serum high-sensitivity C-reactive protein levels were determined in adult patients during the febrile, convalescent and defervescent stages of dengue serotype-2 (DENV-2) infection, and compared with those of age--matched healthy and non-dengue febrile subjects. In vitro studies were performed to examine the effects of live and heat-inactivated DENV-2 on the activities and expression of 5-lipoxygenase in human neutrophils. Results Plasma leukotriene B4 were elevated during the febrile stages of dengue infection compared to those during convalescence and in study controls. Plasma leukotriene B4 also correlated with serum high-sensitivity C-reactive protein in dengue patients (febrile, r = 0.91, p < 0.001; defervescence, r = 0.87, p < 0.001; convalescence, r = 0.87, p < 0.001). Exposure of human neutrophils to DENV-2 resulted in a significant rise in leukotriene B4; the extent of increase, however, did not differ between exposure to live and heat-inactivated DENV-2. Preincubation of either live or heat-inactivated DENV-2 resulted in reduced release of leukotriene B4 release by neutrophils, indicating that contact with dengue antigens (and not replication) triggers the neutrophil response. Production of leukotriene B4 was associated with an increase in 5-lipoxygenase expression in human neutrophils; addition of MK886 (a 5- lipoxygenase activating protein inhibitor) attenuated further increase in leukotriene B4 production. Conclusion These findings provide important clinical and mechanistic data on the involvement of 5- lipoxygenase and its metabolites in dengue infection. Further studies are needed to elucidate the therapeutic implications of these findings. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- The role of oxidative damage in the pathogenesis of metabolic syndrome is poorly understood. RESEARCH DESIGN AND METHODS -- A detailed cross-sectional study was performed to assess the relationship between lipid oxidation products, γ -glutamyltransferase, high-sensitivity C-reactive protein (hs-CRP), and phospholipase activities with respect to the metabolic status in a cohort of otherwise healthy individuals. RESULTS -- A total of 179 individuals (87 men and 92 women) aged 43 ± 14 years (mean ± SD) participated in this study. There were no differences in the levels of plasma F2-isoprostanes, hydroxyeicosatetraenoic acids, cholesterol oxidation products, and phospholipase activities in individuals with features of metabolic syndrome. In multivariate analyses, serum hs-CRP was a consistent independent predictor of metabolic syndrome. CONCLUSIONS -- Minimal changes were observed in multiple markers of oxidative damage in a well-characterized cohort of individuals with features of metabolic syndrome. [ABSTRACT FROM AUTHOR]

With the restoration of You-Know-Who to full corporeal form, the practice of the dark arts may lead to multitudes being charmed, befuddled and confounded. At present, muggle ethics dictate that aid may be rendered in a life- or limb-threatening situation, but the margins are blurred when neither is at stake. Muggle and wizard healers, fearful of being labelled ambulance chasers, may shy away from approaching those who remain blissfully unaware of their illnesses. We describe 4 case studies in which we intervened as muggle healers, to salutary effect. The afflicted were healed or helped, without bringing the weight of the Ministries of Magic or Magical Healing upon us. We advocate a spirit of cooperation between muggle and magical folk, mindful of the strengths that the healing arts from each community have to offer. As long as the intent is beneficent, healers or even the wizard or muggle on the street may intervene and render aid to the afflicted. [ABSTRACT FROM AUTHOR]

In this article the author discusses the physician's duty of care with emphasis on whether the ethical imperative to treat exists only in a medical emergency or after the establishment of a formal doctor-patient relationship. He points the argument that doctors have a moral and legal obligation to render assistance in the event of a medical emergency. He added that the said relationship likewise provides a doctor with the moral and legal imperative to practice good medicine.

Background: Despite the global availability of multiple sclerosis (MS) treatments, accessing and financing them in Southeast Asia (SEA) remains a challenge. This descriptive survey-based study aimed to describe the current state of MS treatment access and local access dynamics within this region., Methods: The survey questionnaire, comprising of 15 closed-ended and five open-ended questions, was developed by three neurologists with expertise in MS and routine MS patient management, or had training in neuroimmunology. Questionnaire development was guided by the recent Atlas of MS and in alignment with the Access to Treatment framework, focusing on MS diagnosis and treatment issues in SEA. Fifteen neurologists experienced in managing MS across the region were identified as key informants for this study., Results: All fifteen neurologists participated in the survey via email and videoconferencing between January 2020 and February 2023, which included the following countries: Brunei, Cambodia, Indonesia, Malaysia, Myanmar, Lao PDR, Philippines, Singapore, Thailand, Timor-Leste, and Vietnam. All had at least five years of experience in managing MS patients and six had previously completed a neuroimmunology fellowship programme. SEA countries showed disparities in healthcare financing, availability of neurologists, MS treatments, and investigative tools. Access to MS disease-modifying treatments (DMTs) is hindered by high cost, lack of MS specialists, and weak advocacy efforts. On-label DMTs are not listed as essential medicines regionally except for interferon beta1a and teriflunomide in Malaysia. On-label monoclonals are available only in Malaysia, Singapore, and Thailand. Generic on-label DMTs are unavailable due to lack of distributorship and expertise in using them. Off-label DMTs (azathioprine, methotrexate, and rituximab) predominate in most SEA countries. Other challenges include limited access to investigations, education, and knowledge about DMTs among general neurologists, and absence of registries and MS societies. Patient champions, communities, and MS organisations have limited influence on local governments and pharmaceutical companies. Despite its increasing prevalence, there is a lack of concerted priority setting due to MS being perceived as a rare, non-communicable disease., Conclusion: This study highlights the distinct dynamics, challenges, and research gaps within this region, and provides suggestions to improve MS diagnosis, education, and medicine access., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tianrong Yeo reports a relationship with Edanz Group Ltd that includes: consulting or advisory. Tianrong Yeo reports a relationship with Merck & Co Inc that includes: consulting or advisory and travel reimbursement. Tianrong Yeo reports a relationship with EUROIMMUN Medizinische Labordiagnostika AG that includes: consulting or advisory. Tianrong Yeo reports a relationship with Novartis that includes: consulting or advisory. Tianrong Yeo reports a relationship with Terumo BCT that includes: consulting or advisory. Tianrong Yeo reports a relationship with ASEAN Neurological Association that includes: consulting or advisory. Tianrong Yeo reports a relationship with National Medical Research Center that includes: funding grants. Tianrong Yeo reports a relationship with Roche that includes: funding grants. Joanna Laurson-Doube reports a relationship with Bristol Myers Squibb Co that includes: funding grants. Joanna Laurson-Doube reports a relationship with Sanofi that includes: funding grants. Joanna Laurson-Doube reports a relationship with Merck & Co Inc that includes: funding grants. Joanna Laurson-Doube reports a relationship with Viatris that includes: funding grants. Joanna Laurson-Doube reports a relationship with Novartis that includes: funding grants. Joanna Laurson-Doube reports a relationship with Biogen that includes: funding grants. Joanna Laurson-Doube reports a relationship with Roche that includes: funding grants., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Accumulating data suggest blood biomarkers could inform stroke etiology., Objective: The purpose of this study was to investigate the performance of multiple blood biomarkers in elucidating stroke etiology with a focus on new-onset atrial fibrillation (AF) and cardioembolism., Methods: Between January and December 2017, information on clinical and laboratory parameters and stroke characteristics was prospectively collected from ischemic stroke patients recruited from the National University Hospital, Singapore. Multiple blood biomarkers (N-terminal pro-brain natriuretic peptide [NT-proBNP], d-dimer, S100β, neuron-specific enolase, vitamin D, cortisol, interleukin-6, insulin, uric acid, and albumin) were measured in plasma. These variables were compared with stroke etiology and the risk of new-onset AF and cardioembolism using multivariable regression methods., Results: Of the 515 ischemic stroke patients (mean age 61 years; 71% men), 44 (8.5%) were diagnosed with new-onset AF, and 75 (14.5%) had cardioembolism. The combination of 2 laboratory parameters (total cholesterol ≤169 mg/dL; triglycerides ≤44.5 mg/dL) and 3 biomarkers (NT-proBNP ≥294 pg/mL; S100β ≥64 pg/mL; cortisol ≥471 nmol/l) identified patients with new-onset AF (negative predictive value [NPV] 90%; positive predictive value [PPV] 73%; area under curve [AUC] 85%). The combination of 2 laboratory parameters (total cholesterol ≤169 mg/dL; triglycerides ≤44.5 mg/dL) and 2 biomarkers (NT-proBNP ≥507 pg/mL; S100β ≥65 pg/mL) identified those with cardioembolism (NPV 86%; PPV 78%; AUC 87%). Adding clinical predictors did not improve the performance of these models., Conclusion: Blood biomarkers could identify patients with increased likelihood of cardioembolism and direct the search for occult AF., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Biomarkers provide critical mechanistic insights to key biologic processes that occur during cerebral ischemia which, when carefully applied, can improve clinical decision-making in acute stroke management. The translation of a blood-based biomarker in ischemic stroke to clinical practice is challenging, in part, due to the complexity of ischemic stroke pathogenesis and the presence of a blood-brain barrier that restricts the release of brain-specific markers into the circulation. The pathologic and clinical aspects of ischemic stroke are described in this review, where a non-exhaustive list of biomarkers that interrogate different aspects of ischemic stroke such as oxidative damage, inflammation, thrombus formation, cardiac function and brain injury are described. The potential roles of these biomarkers are further examined under different clinical scenarios aimed at (1) averting the risk of hemorrhagic transformation, (2) identifying individuals at risk of early neurologic deterioration and malignant infarction, (3) aiding in the diagnosis of ischemic stroke and its differentiation from other stroke mimics, (4) guiding the search for stroke etiology, and (5) assessing stroke risk within the community. Researchers should explore the roles of stroke biomarkers to enhance clinical decision-making that is presently largely based on intuition and subjective reasoning., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: To evaluate the use of intravenous immunoglobulin (IVIG) in preventing relapses in patients with neuromyelitis optica (NMO) and its spectrum disorders (NMOSDs)., Methods: Six NMO/NMOSD patients who were treated with IVIG induction dose followed by 2- to 3- monthly infusions were retrospectively identified. Annualized relapse rates (ARR) and Expanded Disability Status Scale (EDSS) pre- and post-IVIG were recorded., Results: Median number of relapses and median ARR significantly reduced from 8.0 to 1.0 and 0.75 to 0.15 (p<0.05) respectively. Median EDSS of 6.5 remained the same. Median duration of treatment was 4.0 years., Conclusion: IVIG may be used to reduce the relapse frequency in patients with NMO/NMOSD., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Considerable data implicate oxidative damage in influenza pathogenesis. We examined temporal changes in oxidative damage using accurate biomarkers in an adult cohort with acute influenza infection and their relationships with clinical parameters. Clinical information and blood samples were collected during their acute illness and 3 months later. A fatigue questionnaire was administered 3 months following influenza infection. Thirty-five patients (mean age, 34 years) with polymerase chain reaction-confirmed influenza A infection were included; all patients returned for follow-up assessments. Adjusted levels of plasma F2-isoprostanes, total hydroxyeicosatetraenoic products (HETEs), 7β-hydroxycholesterol and 7-ketocholesterol, serum gamma-glutamyltransferase, and high-sensitivity C-reactive protein (hsCRP) were increased during the acute illness compared with age-matched controls. Despite clinical recovery, levels of these biomarkers remained higher at month 3 compared with controls. A proportion of patients had persistent symptoms such as fatigue (23%), myalgia (14%), and arthralgia (11%) at month 3. Patients with significant fatigue had higher baseline levels of plasma F2-isoprostanes, F4-neuroprostanes, and total HETEs compared to those without fatigue. By contrast, patients with persistent arthralgia and myalgia had higher baseline levels of serum hsCRP compared to those without these symptoms. Our observations lead to the hypothesis that oxidative damage participates in the pathogenesis of influenza infection and postinfectious fatigue.

Evidence on the efficacy of high-dose coenzyme Q10 (CoQ10) in Parkinson's disease (PD) is conflicting. An open-label dose-escalation study was performed to examine the effects of CoQ10 on biomarkers of oxidative damage and clinical outcomes in 16 subjects with early idiopathic PD. Each dose (400, 800, 1200, and 2400 mg/day) was consumed daily for 2 weeks. High-dose CoQ10 was well tolerated and improvements in the total Unified Parkinson's Disease Rating Scale (median, 37 vs. 27; p=0.048) were observed following study completion. Plasma F2-isoprostanes (adjusted for arachidonate) were significantly reduced in the 400-1200 mg/day dose range, but increased at 2400 mg/day dosage. A similar pattern of change was observed with serum phospholipase A2 activities. Levels of plasma all trans-retinol, plasma total tocopherol, serum uric acid, and serum total cholesterol were unchanged despite an increase in the CoQ10 dosage. Subjects with symptomatic benefits from CoQ10 (decrease in total UPDRS >10 points) had lower baseline plasma ubiquinol (p=0.07, Mann-Whitney U test) and decreased F2-isoprostanes per unit arachidonate (p=0.04, Wilcoxon Signed-Ranks test). These results lead to the hypothesis that the therapeutic response to CoQ10 depends on baseline levels of ubiquinol and whether the dosage of CoQ10 used can ameliorate the burden of oxidative damage.

The purpose of this study was to evaluate the use of Framingham risk scores (FRRs) to identify high-risk individuals with biochemical evidence of increased oxidative damage, who may benefit from antioxidant therapies. A bimodal change in plasma F2-isoprostane levels was observed with cardiovascular risk categories, while plasma neuroprostanes, 7α-hydroxycholesterol, and serum γ-glutamyltransferase levels were higher among individuals at high risk of cardiovascular events (Framingham score, > 36). Total plasma hydroxyeicosatetraenoic acid products (HETEs) and serum high-sensitivity CRP (hsCRP) levels were consistently higher across Framingham risk categories. Multivariable analysis identified plasma 7α-hydroxycholesterol (odds ratio (OR), 1.06; 95% confidence interval (CI), 1.03-1.10) and γ-glutamyltransferase (OR, 1.02; 95% CI, 1.01-1.03) as significant predictors of high cardiovascular risk (Framingham score, > 36), accounting for approximately 21% of its variation. Cardiovascular risk scores are useful to identify individuals with high burden of oxidative damage who may benefit from antioxidant therapy.

Background: It is unclear whether changes in insulin sensitivity or arterial stiffness in cigarette smokers could explain the link between cigarette smoking and diabetes mellitus. The purpose of the study was to evaluate the acute effects of cigarette smoking on insulin resistance and arterial stiffness in a cohort of young healthy adults., Methods: Metabolic risk components, hemodynamic parameters, plasma nitrite/nitrate and high-sensitivity C-reactive protein (hsCRP) levels, were compared between smokers and age- and gender-matched controls (non-smokers). In smokers, these levels were determined 8-h following cigarette abstinence and an hour after smoking., Results: One hundred nineteen smokers and age-matched non-smokers (mean age, 32 years; 83% men) were included in this study. Compared with non-smokers, smokers had a significantly higher number of abnormal metabolic risk components, HOMA-IR index and total nitrite/nitrate levels. There were no differences in brachial/central blood pressure, augmentation index and hsCRP between smokers and non-smokers. An hour after smoking, smokers had significantly higher levels of HOMA-IR, total nitrite/nitrate, hsCRP and heart rate compared with baseline levels. By contrast, brachial/central blood pressure and augmentation index were unchanged after cigarette smoking. Baseline vascular and insulin resistance status predicted the extent of rise in the HOMA-IR and augmentation indices acutely after cigarette smoking (adjusted R(2) 0.358 and 0.124, p < 0.001 respectively)., Conclusions: Individuals with more advanced vascular damage and insulin resistance are vulnerable to the acute effects of cigarette smoking., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: There is considerable controversy about what constitutes optimal zinc intakes in patients with type 2 diabetes mellitus. Several studies suggest that higher zinc intakes improve vascular function and decrease oxidative damage. We aimed to assess the effects of zinc supplementation using a range of reliable biomarkers of oxidative damage and vascular function in patients with type 2 diabetes., Methods: Forty male type 2 diabetic patients were supplemented either with 240 mg/day of zinc as zinc gluconate (n=20) or with placebo (n=20) for 3 months. Blood and spot urine samples were taken at baseline, days 3 and 7, months 1, 2 and 3 during supplementation and 1 month after cessation. Serum zinc, reliable biomarkers of oxidative damage (F(2)-isoprostanes, neuroprostanes, cholesterol oxidation products, allantoin) as well as hydroxyeicosatetraenoic acid products and vascular-related indices (augmentation index, pulse wave velocity and aortic pressure) were measured., Results: Despite significantly higher levels of serum zinc in the treatment group, markers of oxidative damage, levels of hydroxyeicosatetraenoic acid products and vascular indices were unchanged by zinc supplementation during the four-month study period., Conclusion: Improving the zinc status in patients with type 2 diabetes with normal zinc levels did not have any impact on oxidative damage and vascular function, and such supplementation may not be generally beneficial in these individuals., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Botulinum toxin (BTX), the exotoxin of the obligate anaerobe, Clostridium botulinum, is used to ameliorate pain and treat conditions associated with glandular, smooth and skeletal muscle overactivity. The benefits derived from the injection of BTX may be negated by unintended weakness of uninjected muscles. Performance of BTX injections may be facile, requiring only surface marking or clinical-localisation techniques but may be more technically demanding, necessitating the use of equipment, such as electromyography (EMG) or ultrasonography (U/S). Less often, endoscopic, fluoroscopic or computed tomographic (CT) guidance may be required. Despite evidence to support the efficacy of BTX injections in treating many conditions, there is no evidence to support the superiority of any one injection technique over needle localisation using surface anatomy. This is possibly due to the lack of well-designed controlled studies, that is, current studies are hampered by small patient numbers, lack of consistency of injection technique and the application of different rating scales. Intuitively, certain injection techniques are more suited to injection of specific muscles or conditions, for example, U/S or passive-monitoring EMG should be used to treat cervical dystonia, active-monitoring EMG applied for strabismus injections, whereas either active-monitoring EMG or endoscopy is indicated when giving BTX for spasmodic dysphonia. Finally, electrical-stimulation EMG or U/S (or a combination of both) would be most suitable when injecting the forearm muscles for spasticity or writer's cramps., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Cigarette smoking predisposes to the development of multiple diseases involving oxidative damage. We measured a range of oxidative damage biomarkers to understand which differ between smokers and nonsmokers and if the levels of these biomarkers change further during the act of smoking itself. Despite overnight abstinence from smoking, smokers had higher levels of plasma total and esterified F(2)-isoprostanes, hydroxyeicosatetraenoic acid products (HETEs), F(4)-neuroprostanes, 7-ketocholesterol, and 24- and 27-hydroxycholesterol. Levels of urinary F(2)-isoprostanes, HETEs, and 8-hydroxy-2'-deoxyguanosine were also increased compared with age-matched nonsmokers. Several biomarkers (plasma free F(2)-isoprostanes, allantoin, and 7β-hydroxycholesterol and urinary F(2)-isoprostane metabolites) were not elevated. The smokers were then asked to smoke a cigarette; this acute smoking elevated plasma and urinary F(2)-isoprostanes, plasma allantoin, and certain cholesterol oxidation products compared to presmoking levels, but not plasma HETEs or urinary 8-hydroxy-2'-deoxyguanosine. Smokers showed differences in plasma fatty acid composition. Our findings confirm that certain oxidative damage biomarkers are elevated in smokers even after a period of abstinence from smoking, whereas these plus some others are elevated after acute smoking. Thus, different biomarkers do not measure identical aspects of oxidative stress., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Oxidative damage has been implicated in the pathogenesis of Parkinson disease (PD) but the literature data are confusing. Using products of lipid and DNA oxidation measured by accurate methods, we assessed the extent of oxidative damage in PD patients. The levels of plasma F(2)-isoprostanes (F(2)-IsoPs), hydroxyeicosatetraenoic acid products (HETEs), cholesterol oxidation products, neuroprostanes (F(4)-NPs), phospholipase A(2) (PLA(2)) and platelet activating factor-acetylhydrolase (PAF-AH) activities, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and serum high-sensitivity C-reactive protein were compared in 61 PD patients and 61 age-matched controls. The levels of plasma F(2)-IsoPs, HETEs, 7beta-and 27-hydroxycholesterol, 7-ketocholesterol, F(4)-NPs, and urinary 8-OHdG were elevated, whereas the levels of plasma PLA(2) and PAF-AH activities were lower, in PD patients compared to controls (p< 0.05). The levels of plasma F(2)-IsoPs, HETEs, and urinary 8-OHdG were higher in the early stages of PD (p trend< 0.05). There was a significant negative correlation between the cumulative intake of levodopa and urinary 8-OHdG (r= -0.305, p= 0.023) and plasma total HETEs (r= -0.285, p= 0.043). Oxidative damage markers are systemically elevated in PD, which may give clues about the relation of oxidative damage to the onset and progression of PD., (Copyright 2009 Elsevier Inc. All rights reserved.)

Background: We performed a case-control study to assess the relationship between vascular endothelial growth factor (VEGF) and its soluble receptors (sVEGFR-1 and 2) in adult patients with dengue fever (DF) and dengue hemorrhagic fever (DHF)., Methods: We recruited 60 adult patients (34 DF and 26 DHF) with serologically-confirmed dengue infections, 10 patients with non-hemorrhagic infections, and 31 community-based healthy volunteers. The levels of VEGF, sVEGFR-1, and sVEGFR-2 were measured and the differences in these markers were compared using one-way analysis of variance (ANOVA), which was adjusted for multiple comparisons., Results: We observed lower VEGF levels in DF and DHF compared to study controls (p<0.01). sVEGFR-1 was higher in DHF than DF, whilst sVEGFR-2 was lower in DF and DHF compared to study controls (all p<0.01). In DHF, lower VEGF levels were observed in older patients. The use of a single marker, sVEGFR-1>350 pg/ml, was predictive of DHF., Conclusion: The changes in VEGF and its soluble receptors highlight the importance of vascular permeability cytokines in the pathogenesis of DHF.

Oxidative stress may be important in the pathogenesis of dengue infection. Using accurate markers of oxidative damage, we assessed the extent of oxidative damage in dengue patients. The levels of hydroxyeicosatetraenoic acid products (HETEs), F(2)-isoprostanes (F(2)-IsoPs), and cholesterol oxidation products (COPs) were measured in 28 adult dengue patients and 28 age-matched study controls during the febrile, defervescent, and convalescent stages of infection. We compared the absolute and the percentage change in these markers in relation to key clinical parameters and inflammatory markers. The levels of total HETEs and total HETEs/arachidonate, total F(2)-IsoPs/arachidonate, and COPs/cholesterol were higher during the febrile compared to the convalescent level. Total HETEs correlated positively with admission systolic blood pressure (r=0.52, p<0.05), whereas an inverse relationship was found between 7beta-hydroxycholesterol and systolic and diastolic blood pressure (r=-0.61 and -0.59, respectively, p<0.01). The urinary F(2)-IsoP level was higher in urine during the febrile stage compared to the convalescent level. Despite lower total cholesterol levels during the febrile stage compared to convalescent levels, a higher percentage of cholesterol was found as COPs (7beta-, 24-, and 27-hydroxycholesterol). The levels of platelet-activating factor-acetylhydrolase activity, vascular cellular adhesion molecule-1, tumor necrosis factor-alpha, and high-sensitivity C-reactive protein were higher during the febrile stage compared to their convalescent levels (p<0.01). Markers of oxidative damage are altered during the various stages of dengue infection.

Introduction: Singaporeans are superstitious, and medical staff are no exception to the rule. We conducted a survey to determine the prevalence of superstitious beliefs and practices amongst doctors, nurses and medical students in Singapore., Methods: Internet and face-to-face surveys of 68 respondents, all of whom completed the survey after being threatened with curses and hexes., Results: Sixty-eight doctors, nurses and medical students responded to our survey. Only 11 admitted to being superstitious, yet 31 believed in the ill-fortune associated with eating bao or meat dumplings, 6 in the nefarious powers of black (5) or red (1) outfits on call, and 14 believed that bathing (6 insisting on the powers of the seven-flower bath) prior to the onset of a call portended good fortune, in terms of busy-ness of a call. Twenty-four believed in "black clouds", i.e. people who attracted bad luck whilst on call, and 32 refused to mouth the words "having a good call" until the day after the event. We discovered 2 hitherto undescribed and undiscovered superstitions, namely the benefits of eating bread and the need to avoid beef, for the good and ill fortune associated with their ingestion., Discussion: Superstitious practices are alive and well in modern-day Singapore, the practice not necessarily being restricted to the poorly-educated or foolish.

Background: Dengue infection can result in severe ocular complications. We prospectively studied the range of ocular symptoms in a cohort of patients with dengue infection., Methods: We included adult patients with serologically confirmed dengue infection who received clinical care at the National University Hospital, Singapore. They were assessed for demographic characteristics, ocular symptoms, laboratory parameters and dengue severity. Patients with two or more ocular symptoms were referred to an ophthalmologist and underwent full ophthalmologic examination that included visual acuity, slit-lamp examination and indirect fundoscopic examination. Descriptive and logistic regression analyses were performed and statistical significance was set at p<0.05., Results: One hundred and fifty-six patients, aged (S.D.) 33.94 (12.7) years, consisting of 89 (57.1%) males and 67 (42.9%) females, participated in this study. They reported ocular symptoms, such as eye strain (30%), retro-ocular pain (20%), blurring of vision (10%), double vision (3%), foreign body sensation (3%), eye flashes (2%) and floaters (1%). Multivariate analysis identified white cell count (odds ratio, OR 0.531; 95% CI 0.292, 0.963) and serum albumin (OR 0.758; 95% confidence intervals, CI 0.618, 0.928) as significant predictors of clinically significant ocular symptoms. The triad of symptoms (eye flashes, floaters and blurring of vision) was highly predictive for the development of retinal hemorrhages (positive predictive value 100%)., Conclusions: Dengue virus results in a spectrum of ocular manifestations, ranging from non-specific symptoms to severe retinal hemorrhages. Further studies are needed to validate the triad of ocular symptoms as a screening tool for severe ocular complications following dengue infection.

Background: Although the acute manifestations of dengue are well known, few studies have assessed the long-term consequences of dengue infection. We prospectively studied the incidence and factors associated with fatigue in a cohort of patients following dengue infection., Methods: We included patients with serologically confirmed dengue infection admitted to the National University Hospital, Singapore, during a dengue outbreak from October-November 2005. The severity of dengue was graded as dengue fever, dengue haemorrhagic fever and dengue shock syndrome. A follow-up telephone interview was performed two months following hospital discharge, where a Fatigue Questionnaire was administered. The presence of significant fatigue was considered as the main outcome measure. Significance was assessed at P<0.05., Results: One hundred twenty-seven patients, 71 (55.9%) males and 56 (44.1%) females, of mean age 36.06 years (range, 16-70; S.D., 13.722), participated in this study. Twenty-five (19.7%) patients had dengue haemorrhagic fever and the remaining 102 (80.3%) had dengue fever. In multivariate analysis, increased age, female sex, the presence of chills, and the absence of rashes were significantly associated with the development of fatigue post-dengue infection. There was no significant association between fatigue and dengue severity., Conclusions: This observation represents the first systematic evidence that dengue can result in clinical disease beyond the acute phases of infection. Host factors, such as age and sex may be important in the pathogenesis of this clinical entity.

With the restoration of You-Know-Who to full corporeal form, the practice of the dark arts may lead to multitudes being charmed, befuddled and confounded. At present, muggle ethics dictate that aid may be rendered in a life-or limb-threatening situation, but the margins are blurred when neither is at stake. Muggle and wizard healers, fearful of being labelled ambulance chasers, may shy away from approaching those who remain blissfully unaware of their illnesses. We describe 4 case studies in which we intervened as muggle healers, to salutary effect. The afflicted were healed or helped, without bringing the weight of the Ministries of Magic or Magical Healing upon us. We advocate a spirit of cooperation between muggle and magical folk, mindful of the strengths that the healing arts from each community have to offer. As long as the intent is beneficent, healers or even the wizard or muggle on the street may intervene and render aid to the afflicted.

Ailments afflicting wizarding folk are underreported in the muggle world. The recent integration of muggles and magical folk with the return of You-Know-Who (aka He Who Must Not Be Named) may result in a similar affliction of inhabitants of both worlds. We describe interesting maladies afflicting muggles and wizarding folk alike, arising from the use and misuse of magic. We also provide a basic glossary of magical ailments, and describe their muggle corollaries. Further studies will hopefully result in the development of immunity against the unforgivable curses.