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Leptospirosis, a notifiable endemic disease in Malaysia, has higher mortality rates than regional dengue fever. Diverse clinical symptoms and limited diagnostic methods complicate leptospirosis diagnosis. The demand for accurate biomarker-based diagnostics is increasing. This study investigated the plasma proteome of leptospirosis patients with leptospiraemia and seroconversion compared with dengue patients and healthy subjects using isobaric tags for relative and absolute quantitation (iTRAQ)-mass spectrometry (MS). The iTRAQ analysis identified a total of 450 proteins, which were refined to a list of 290 proteins through a series of exclusion criteria. Differential expression in the plasma proteome of leptospirosis patients compared to the control groups identified 11 proteins, which are apolipoprotein A-II (APOA2), C-reactive protein (CRP), fermitin family homolog 3 (FERMT3), leucine-rich alpha-2-glycoprotein 1 (LRG1), lipopolysaccharide-binding protein (LBP), myosin-9 (MYH9), platelet basic protein (PPBP), platelet factor 4 (PF4), profilin-1 (PFN1), serum amyloid A-1 protein (SAA1), and thrombospondin-1 (THBS1). Following a study on a verification cohort, a panel of eight plasma protein biomarkers was identified for potential leptospirosis diagnosis: CRP, LRG1, LBP, MYH9, PPBP, PF4, SAA1, and THBS1. In conclusion, a panel of eight protein biomarkers offers a promising approach for leptospirosis diagnosis, addressing the limitations of the "one disease, one biomarker" concept.

Optimizing Resistance spot welding, often used as a time and cost-effective process in many industrial sectors, is very time-consuming due to the obscurity inherent within process with numerous interconnected welding parameters. Small changes in values will give effect to the quality of welds which actually can be easily analysed using application tool. Unfortunately, existing software to optimize the parameters are expensive, licensed and inflexible which makes small industries and research centres refused to acquire. In this study, application tool using open-sourced and customized algorithm based on artificial neural networks (ANN) was developed to enable better, fast, cheap and practical predictions of major parameters such as welding time, current and electrode force on tensile shear load bearing capacity (TSLBC) and weld quality classifications (WQC). A supervised learning algorithm implemented in standard backpropagation neural network gradient descent (GD), stochastic gradient descent (SGD) and Levenberg-Marquardt (LM) was constructed using TensorFlow with Spyder IDE in python language. All the display and calculation processes are developed and compiled in the form of application tool of graphical user interface (GUI). Results showed that this low-cost application tool Q-Check based on ANN models can predict with 80% training and 20% test set on TSLBC with an accuracy of 87.220%, 92.865% and 93.670% for GD, SGD and LM algorithms respectively while on WQC 62.5% for GD and 75% for both SGD and LM. It is also expected that tool with flexible GUI can be widely used and enhanced by practitioner with minimum knowledge in the domain., (© 2023. The Author(s).)

The Modified Ashworth Scale (MAS) is commonly used to assess spasticity in clinics. The qualitative description of MAS has resulted in ambiguity during spasticity assessment. This work supports spasticity assessment by providing measurement data acquired from wireless wearable sensors, i.e., goniometers, myometers, and surface electromyography sensors. Based on in-depth discussions with consultant rehabilitation physicians, eight (8) kinematic, six (6) kinetic, and four (4) physiological features were extracted from the collected clinical data from fifty (50) subjects. These features were used to train and evaluate the conventional machine learning classifiers, including but not limited to Support Vector Machine (SVM) and Random Forest (RF). Subsequently, a spasticity classification approach combining the decision-making logic of the consultant rehabilitation physicians, SVM, and RF was developed. The empirical results on the unknown test set show that the proposed Logical-SVM-RF classifier outperforms each individual classifier, reporting an accuracy of 91% compared to 56-81% achieved by SVM and RF. A data-driven diagnosis decision contributing to interrater reliability is enabled via the availability of quantitative clinical data and a MAS prediction.

The Machine Learning Model (MLM) has garnered popularity in rehabilitation, ranging from developing algorithms in outcome prediction, prognostication, and training artificial intelligence. High-quality data plays a critical role in algorithm development. Limited studies have explored factors that may influence the MLM algorithm performance in predicting spasticity severity level. The objectives of this study were to train and validate a MLM algorithm for spasticity assessment and determine the algorithm's prediction performance in predicting ambiguous spasticity datasets. Forty-seven persons with central nervous system pathology that fulfilled the inclusion and exclusion criteria were recruited. Four biomechanical properties of spasticity were obtained using off-the-shelf wearable sensors. The data were analyzed individually, and ambiguous datasets were separated. The acceptable inertial data were used to train and validate MLM in predicting spasticity. The trained and validated MLM algorithm was later deployed to predict the ambiguous spasticity datasets. A series of MLM were applied, including Support Vector Machine, Decision Tree, and Random Forest. The MLM's performance accuracy of the validation data was 96%, 52%, and 72%, respectively. The validated MLM accuracy performance level predicting ambiguous datasets reduces to 20%, 23%, and 23%, respectively. This study elucidates data biases and variances of disease background, pathophysiological and anatomical factors that have to be considered in MLM training.

Open set recognition (OSR) models need not only discriminate between known classes but also detect unknown class samples unavailable during training. One promising approach is to learn discriminative representations over known classes with strong intra-class similarity and inter-class discrepancy. Then, the powerful class discrimination learned from the known classes can be extended to known and unknown classes. Without appropriate regularization, however, the model may learn representations trivially, collapsing unknown class representations to the known class ones. To resolve this problem, we propose Divergent Angular Representation (DivAR) based on two approaches. Firstly, DivAR maximizes its representational discrimination between known classes via a highly discriminative loss. Secondly, to ensure separation between known and unknown classes in the representation space, DivAR boosts the directional variation of representations over global samples. In addition, self-supervision is leveraged to improve the representation's robustness and extend DivAR to one-class classification. Moreover, unlike other OSR methods that require an extra machinery for inference, DivAR learns and infers in a single module. Extensive experiments on generic image datasets demonstrate the plausibility and effectiveness of DivAR for both OSR and One-Class Classification (OCC) problems.

There are limited data on the fluid balance characteristics and fluid replenishment behaviors of high-performance adolescent athletes. The heterogeneity of hydration status and practices of adolescent athletes warrant efficient approaches to individualizing hydration strategies. This study aimed to evaluate and characterize the hydration status and fluid balance characteristics of high-performance adolescent athletes and examine the differences in fluid consumption behaviors during training. In total, 105 high-performance adolescent athletes (male: 66, female: 39; age 14.1 ± 1.0 y) across 11 sports had their hydration status assessed on three separate occasions-upon rising and before a low and a high-intensity training session (pre-training). The results showed that 20-44% of athletes were identified as hypohydrated, with 21-44% and 15-34% of athletes commencing low- and high-intensity training in a hypohydrated state, respectively. Linear mixed model (LMM) analyses revealed that athletes who were hypohydrated consumed more fluid (F (1.183.85)) = 5.91, ( p = 0.016). Additional K-means cluster analyses performed highlighted three clusters: "Heavy sweaters with sufficient compensatory hydration habits," "Heavy sweaters with insufficient compensatory hydration habits" and "Light sweaters with sufficient compensatory hydration habits". Our results highlight that high-performance adolescent athletes with ad libitum drinking have compensatory mechanisms to replenish fluids lost from training. The approach to distinguish athletes by hydration characteristics could assist practitioners in prioritizing future hydration intervention protocols.

Conventional ankle rehabilitation exercises can be monotonous and repetitive. The use of robots and games can complement the existing practices, provide an engaging environment for the patient and alleviate the physiotherapist's workload. This paper presents an ankle rehabilitation robot that uses two nitinol wire actuators and a Pong game to provide foot plantarflexion and dorsiflexion exercises. Nitinol is a type of smart material that has high volumetric mechanical energy density and can produce translational motion. A two-state discrete antagonistic control is proposed to manipulate the actuators. The system was tested on healthy participants and stroke patients. The results showed that the robot was safe and compliant. The robot did not forcefully plantarflex or dorsiflex the foot when the participant exerted opposing force. The actuators worked antagonistically to flex to the foot as intended, in sync with the up and down motions of the player's bat in the game. These behaviors demonstrated the feasibility of a nitinol-based ankle rehabilitation robot and a simple and yet intuitive game in providing interactive rehabilitation exercise. The robot is expected to enhance the patient's experience, participation and compliance to the rehabilitation routine and to quantitatively monitor the patient's recovery progress.

Stacking-based deep neural network (S-DNN) is aggregated with pluralities of basic learning modules, one after another, to synthesize a deep neural network (DNN) alternative for pattern classification. Contrary to the DNNs trained from end to end by backpropagation (BP), each S-DNN layer, that is, a self-learnable module, is to be trained decisively and independently without BP intervention. In this paper, a ridge regression-based S-DNN, dubbed deep analytic network (DAN), along with its kernelization (K-DAN), are devised for multilayer feature relearning from the pre-extracted baseline features and the structured features. Our theoretical formulation demonstrates that DAN/K-DAN relearn by perturbing the intra/interclass variations, apart from diminishing the prediction errors. We scrutinize the DAN/K-DAN performance for pattern classification on datasets of varying domains-faces, handwritten digits, generic objects, to name a few. Unlike the typical BP-optimized DNNs to be trained from gigantic datasets by GPU, we reveal that DAN/K-DAN are trainable using only CPU even for small-scale training sets. Our experimental results show that DAN/K-DAN outperform the present S-DNNs and also the BP-trained DNNs, including multiplayer perceptron, deep belief network, etc., without data augmentation applied.

Wounds associated with diabetes mellitus are the most severe co-morbidities, which could be progressed to cause cell necrosis leading to amputation. Statistics on the recent status of the diabetic wounds revealed that the disease affects 15% of diabetic patients, where 20% of them undergo amputation of their limb. Conventional therapies are found to be ineffective due to changes in the molecular architecture of the injured area, urging novel deliveries for effective treatment. Therefore, recent researches are on the development of new and effective wound care materials. Literature is evident in providing potential tools in topical drug delivery for wound healing under the umbrella of nanotechnology, where nano-scaffolds and nanofibers have shown promising results. The nano-sized particles are also known to promote healing of wounds by facilitating proper movement through the healing phases. To date, focuses have been made on the efficacy of silver nanoparticles (AgNPs) in treating the diabetic wound, where these nanoparticles are known to exploit potential biological properties in producing anti-inflammatory and antibacterial activities. AgNPs are also known to activate cellular mechanisms towards the healing of chronic wounds; however, associated toxicities of AgNPs are of great concern. This review is an attempt to illustrate the use of AgNPs in wound healing to facilitate this delivery system in bringing into clinical applications for a superior dressing and treatment over wounds and ulcers in diabetes patients., 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 © 2020 Elsevier B.V. All rights reserved.)

Background: Underestimation of leptospirosis cases is happening in many countries. The most common factor of underreporting is misdiagnosis. Considering the limitations of direct detection of pathogen and serological diagnosis for leptospirosis, clinical features and blood tests though non-specific are usually referred in making presumptive diagnosis to decide disease management., Methods: In this single-centre retrospective study, comparative analysis on clinical presentations and laboratory findings was performed between confirmed leptospirosis versus non-leptospirosis cases., Results: In multivariate logistic regression evidenced by a Hosmer-Lemeshow significance value of 0.979 and Nagelkerke R square of 0.426, the predictors of a leptospirosis case are hypocalcemia (calcium <2.10mmol/L), hypochloremia (chloride <98mmol/L), and eosinopenia (absolute eosinophil count <0.040×10 9 /L). The proposed diagnostic scoring model has a discriminatory power with area under the curve (AUC) 0.761 (p<0.001). A score value of 6 reflected a sensitivity of 0.762, specificity of 0.655, a positive predictive value of 0.38, negative predictive value of 0.91, a positive likelihood ratios of 2.21, and a negative likelihood ratios of 0.36., Conclusion: With further validation in clinical settings, implementation of this diagnostic scoring model is helpful to manage presumed leptospirosis especially in the absence of leptospirosis confirmatory tests., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Human leptospirosis, or commonly known as "rat urine disease" is a zoonotic disease that is caused by the bacteria called Leptospira sp. The incidence rate of leptospirosis has been under-reported due to its unspecific clinical symptoms and the limitations of current laboratory diagnostic methods. Leptospirosis can be effectively treated with antibiotics in the early stage, and it is a curable disease but the accuracy to diagnose the infection is rarely achieved., Methods: The present pilot study investigated plasma protein profiles of leptospirosis patients and compared them against two control groups which consisted of dengue patients and healthy individuals. The plasma protein digests were analyzed using shotgun approach by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Protein abundances were estimated from the exponentially modified protein abundance index (emPAI) values. Plasma proteins in leptospirosis patients with at least two-fold differential expression compared to dengue and healthy control groups (p < 0.05, ANOVA) were identified., Results: Lipopolysaccharide (LPS)-binding protein (LBP) was found to be the only protein that has significant different expression between leptospirosis and the two control groups. The expression levels of leucine-rich alpha-2-glycoprotein (LRG1) and alpha-1-antichymotrypsin (ACT) were different significantly between leptospirosis and healthy group but not to the dengue control group., Conclusion: This is the first plasma proteome-based study on leptospirosis that reports the differential expression of LBP compared to both dengue and healthy controls, which has not been previously reported in the context of leptospirosis., (Copyright © 2019. Published by Elsevier B.V.)

Data in this article are supplementary to the corresponding research article [1]. Morphological features of homogeneous and graded nanofibrous electrospun gelatin scaffolds were observed using scanning electron microscopy. Microstructural properties including fiber diameter and pore size were determined via image analysis, using ImageJ. Uniaxial tensile and fracture tests were performed on both homogeneous and graded scaffolds using a universal testing machine. Stress-strain curves of all scaffolds are presented. Computing software, MATLAB, was used to design fibrous networks with thickness-dependent density and alignment gradients (DAG). Finite element analysis software, Abaqus, was used to determine the effect of the number of layers on the fracture properties of DAG multilayer scaffolds., (© 2019 The Authors.)

Introduction: Dengue virus (DENV), the causative agent of dengue disease exists in sylvatic and endemic ecotypes. The cell morphological changes and viral morphogenesis of two dengue ecotypes were examined at the ultrastructural level to identify potential similarities and differences in the surrogate model of enzootic host., Materials and Methods: Vero cells were inoculated with virus at a multiplicity of infection (MOI) of 0.1. Cell cultures were harvested over a time course and processed for transmission electron microscopic imaging., Results: The filopodia protrusions on cell periphery preceded virus entry. Additionally, sylvatic DENV infection was found spreading slower than the endemic DENV. Morphogenesis of both dengue ecotypes was alike but at different level of efficiency in the permissive cells., Conclusions: This is the first ultrastructural study on sylvatic DENV and this comparative study revealed the similarities and differences of cellular responses and morphogenesis of two dengue ecotypes in vitro. The study revealed the weaker infectivity of sylvatic DENV in the surrogate model of enzootic host, which supposed to support better replication of enzootic DENV than endemic DENV.

Dengue is prevalent in the Asia-Pacific region. Participants of two immunogenicity and safety phase II studies conducted in Singapore and Vietnam (NCT0088089 and NCT00875524, respectively) were followed for up to four years after third vaccine dose of a recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV). Participants (2-45 years) received three doses of CYD-TDV or control at 0, 6, and 12 months. Dengue plaque reduction neutralization test (PRNT 50 ) antibody titers were measured in both studies. Cytokine-producing antigen-specific CD4+ and CD8+ T-cells were quantified to assess cell-mediated immunity (CMI) in Singapore. Post-hoc analyses were carried out for participants aged <9 and ≥9 years old. Related and fatal serious adverse events (SAEs) were collected during long-term follow-up. Of participants who received ≥1 CYD-TDV injection in Singapore (n = 1198) and Vietnam (n = 180), 87% and 92% participants completed long-term follow-up, respectively. At four years, geometric mean titers (GMTs) in participants who received CYD-TDV ranged from 30.2 1/dil (95% CI 23.9-38.3) to 73.7 (49.3-110) 1/dil in Vietnam and 9.73 1/dil (95% CI 8.28-11.4) to 21.8 (18.9-25.1) 1/dil in Singapore. Interferon and interleukin-13 levels were lower at four years than one year post-vaccination but were still present. Tumor necrosis factor- α levels at four years were similar to those after the third vaccine dose. Seropositivity rates were higher at year four in participants who were seropositive vs. seronegative at baseline in both studies. No safety concerns were identified. CYD-TDV demonstrated long-term immunogenicity and was well-tolerated for four years after the third vaccine dose.

Purpose: To investigate the sport-specific performance effect of a brief afternoon nap on high-level Asian adolescent student-athletes who were habitually short sleepers., Methods: Participants were randomly assigned to a nap or nonnap (reading) condition. In the first study, 12 male shooters (13.8 [1.0] y) performed a shooting assessment (20 competition shots) with heart-rate variability monitored during the assessment. In the second study, 19 male track-and-field athletes (14.8 [1.1] y) performed a 20-m sprint-performance assessment. Subjective measures of sleepiness and alertness were obtained in both studies., Results: The brief nap had no effect on any measure of shooting performance (P > .05) or autonomic function (P > .05) in shooters. However, the fastest 20-m sprint times increased significantly (P < .05) from 3.385 (0.128) s to 3.411 (0.143) s, with mean 2-m times trending toward significance (P < .1) among the track-and-field athletes. No significant differences were observed in any other measures., Conclusions: The results of the research indicate varying effects of naps between sport-specific performance measures. Napping had no effect on shooting performance, whereas a negative effect existed in 20-m sprint performance, potentially due to sleep inertia. Considering these findings, some caution is warranted when advocating naps for adolescent athletes.

Dengue virus (DENV) is maintained and circulated in both sylvatic/enzootic and endemic/human cycles and spill over infection of sylvatic DENV into human populations has been reported. Extensive deforestation and increase human activities in forest may increase the risk of human exposure to sylvatic dengue infection and this may become a threat to human. Present study investigated the changes in cell morphology and viral morphogenesis upon infection with sylvatic and endemic ecotypes in human monocytic U-937 cells using transmission electron microscopy. Autophagy, a process that is either pro-viral or anti-viral, was observed in U-937 cells of both infections, however only the replication of endemic DENV was evidenced. An insight into the infection responses of sylvatic progenitors of DENV in susceptible host cells may provide better understanding on dengue emergence in human populations.

Background: The effects of different immunoprophylaxis regimens on cytomegalovirus (CMV) infection in liver transplant recipients (LTRs) have not been compared., Methods: In a cohort, we studied 343 CMV-seropositive recipient (R+) and 83 seronegative donor/recipient (D-/R-) consecutive LTRs from 2004 to 2007. Immunoprophylaxis regimens included steroid-only, steroids plus rabbit anti-thymocyte globulin (rATG), and steroids plus basiliximab. Logistic regression analysis, Cox proportional hazards regression model, and log-rank test were performed for multivariate analysis as appropriate., Results: In total, 164 (39%), 69 (16%), and 193 (45%) patients received steroid-only, basiliximab, and rATG immunoprophylaxis, respectively. CMV infection rates were 15.7% (54/343) in CMV R+ LTRs and 2.4% (2/83) in CMV R- LTRs. Among CMV R+ LTRs who received rATG, the use of at least 6 weeks of CMV prophylaxis reduced the rate of CMV infection from 24.4% (19/78) to 11.7% (9/77). In multivariate analysis, CMV R+ vs D-/R- (odds ratio [OR]=13.1, 95% confidence interval [CI]: 1.8-97.2), rATG >3 mg/kg vs steroid-only induction (OR=1.6, 95% CI: 1.1-2.3), and CMV prophylaxis <6 weeks vs ≥6 weeks (OR=2.7, 95% CI: 1.2-6.4) were independently associated with CMV infection. Subgroup analysis in CMV D-/R+ group who received rATG showed that ≥6 weeks of CMV prophylaxis significantly decreased the risk of CMV infection (OR=1.9, 95% CI: 1.1-3.9; P=.03)., Conclusion: The use of rATG immunoprophylaxis increases the risk of CMV infection in CMV-seropositive LTRs, specifically in the CMV D-/R+ group. Prophylaxis with valganciclovir in this group for at least 6 weeks decreases the risk of CMV infection., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: We conducted a national point prevalence survey (PPS) to determine the prevalence of healthcare-associated infections (HAIs) and antimicrobial use (AMU) in Singapore acute-care hospitals., Methods: Trained personnel collected HAI, AMU, and baseline hospital- and patient-level data of adult inpatients from 13 private and public acute-care hospitals between July 2015 and February 2016, using the PPS methodology developed by the European Centre for Disease Prevention and Control. Factors independently associated with HAIs were determined using multivariable regression., Results: Of the 5415 patients surveyed, there were 646 patients (11.9%; 95% confidence interval [CI], 11.1%-12.8%) with 727 distinct HAIs, of which 331 (45.5%) were culture positive. The most common HAIs were unspecified clinical sepsis (25.5%) and pneumonia (24.8%). Staphylococcus aureus (12.9%) and Pseudomonas aeruginosa (11.5%) were the most common pathogens implicated in HAIs. Carbapenem nonsusceptibility rates were highest in Acinetobacter species (71.9%) and P. aeruginosa (23.6%). Male sex, increasing age, surgery during current hospitalization, and presence of central venous or urinary catheters were independently associated with HAIs. A total of 2762 (51.0%; 95% CI, 49.7%-52.3%) patients were on 3611 systemic antimicrobial agents; 462 (12.8%) were prescribed for surgical prophylaxis and 2997 (83.0%) were prescribed for treatment. Amoxicillin/clavulanate was the most frequently prescribed (24.6%) antimicrobial agent., Conclusions: This survey suggested a high prevalence of HAIs and AMU in Singapore's acute-care hospitals. While further research is necessary to understand the causes and costs of HAIs and AMU in Singapore, repeated PPSs over the next decade will be useful to gauge progress at controlling HAIs and AMU., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Fyn tyrosine kinase has been implicated in the pathogenesis of Alzheimer's disease (AD). We have previously reported that upregulation of the FynT isoform in AD brains was partly associated with astrocyte activation. In this study, we demonstrated selective FynT induction in murine cortex and primary astrocyte culture after prolonged exposure to inflammatory stimulants, suggesting that FynT may mediate persistent neuroinflammation. To delineate the functional role of astrocytic FynT in association with TNF-mediated inflammatory responses, immortalized normal human astrocytes (iNHA) stably expressing FynT kinase constitutively active (FynT-CA) or kinase dead (FynT-KD) mutants were treated with TNF and compared for inflammatory responses using high-throughput real-time RT-PCR and Luminex multi-analyte immunoassays. FynT-CA but not FynT-KD mutant exhibited drastic induction of proinflammatory cytokines and chemokines after prolonged exposure to TNF, which could be attenuated by treating with Fyn kinase inhibitor PP2 or silencing via FynT-specific DsiRNA. FynT kinase activity-dependent induction of PKCδ expression, PKCδ phosphorylation, as well as NFκB activation was detected at the late phase but not the early phase of TNF signaling. In conclusion, selective FynT induction by TNF may facilitate persistent inflammatory responses in astrocytes, which is highly relevant to chronic neuroinflammation in neurodegenerative diseases including but not limited to AD.

Purpose: Adolescent student-athletes face time constraints due to athletic and scholastic commitments, resulting in habitually shortened nocturnal sleep durations. However, there is a dearth of research on the effects of sleep debt on student-athlete performance. The study aimed to (i) examine the habitual sleep patterns (actigraphy) of high-level student-athletes during a week of training and academic activities, (ii) ascertain the effects of habitual sleep durations experienced by high-level student-athletes on psychomotor performance, and (iii) examine the impact of sport training intensities on the sleep patterns of high-level student-athletes that participate in low and high intensity sports., Methods: Sleep patterns of 29 high-level student-athletes (14.7 ± 1.3 yrs) were monitored over 7 days. A psychomotor vigilance task was administered on weekdays to ascertain the effects of habitual sleep durations., Results: Weekend total sleep time was longer than weekdays along with a delay in bedtime, and waketimes. Psychomotor vigilance reaction times on Monday were faster than on Thursday and Friday, with reaction times on Tuesday also faster than on Friday. False starts and lapses were greater on Friday compared with Monday., Conclusion: There was a negative impact of sleep debt on student-athletes' psychomotor performance.

Alzheimer's disease (AD) is the leading cause of dementia in old age and is characterized by the accumulation of β-amyloid plaques and neurofibrillary tangles (NFT). Recent studies suggest that Fyn tyrosine kinase forms part of a toxic triad with β-amyloid and tau in the disease process. However, it is not known whether Fyn is associated with the pathological features of AD in an isoform-specific manner. In this study, we identified selective up-regulation of the alternative-spliced FynT isoform with no change in FynB in the AD neocortex. Furthermore, gene ontology term enrichment analyses and cell type-specific localization of FynT immunoreactivity suggest that FynT up-regulation was associated with neurofibrillary degeneration and reactive astrogliosis. Interestingly, significantly increased FynT in NFT-bearing neurons was concomitant to decreased FynB immunoreactivity, suggesting an involvement of alternative splicing in NFT formation. Furthermore, cultured cells of astrocytic origin have higher FynT to FynB ratio compared to those of neuronal origin. Lastly, primary rat mixed neuron-astrocyte cultures treated with Aβ25-35 showed selective up-regulation of FynT expression in activated astrocytes. Our findings point to an isoform-specific role of FynT in modulating neurofibrillary degeneration and reactive astrogliosis in AD. Fyn kinase is known to interact with β-amyloid and tau, and contributes to Alzheimer's disease pathogenesis. In this study, it is shown that the alternatively spliced FynT isoform is specifically up-regulated in the AD neocortex, with no change in FynB isoform. The increased FynT correlated with markers of neurofibrillary degeneration and reactive astrogliosis. In primary mixed cultures, treatment with amyloid peptides specifically up-regulated FynT in activated astrocytes. This study points to altered alternative splicing as a potential pathogenic mechanism in AD., (© 2015 International Society for Neurochemistry.)

Neurologic complications have long been associated with influenza. A novel strain of influenza A (H1N1) first described in humans to have outbreak potential in 2009 in Mexico went on to become the first influenza pandemic of this century. We evaluated the neurologic complications of the novel influenza A (H1N1) 2009 in children and adults admitted to all public hospitals in Singapore during the influenza A (H1N1) 2009 pandemic between May 2009 and March 2010. All patients were positive for novel H1N1 infection and presented with neurologic symptoms prior to oseltamivir treatment. Ninety-eight patients (median age 6.6 years, range 0.4-62.6) were identified; 90 % were younger than 18 years; 32 % suffered from preexisting neurological, respiratory, or cardiac disease; and 66 % presented with seizures. Of those presenting with seizures, new onset seizures were the most common manifestation (n = 40, 61.5 %), followed by breakthrough seizures (n = 18, 27.7 %) and status epilepticus (n = 7, 10.8 %). Influenza-associated encephalopathy occurred in 20 %. The majority of children (n = 88) presented with seizures (n = 63, 71.6 %), encephalopathy (n = 19, 21.6 %), and syncope (n = 4, 4.5 %). Among adults, a wider range of neurological conditions were seen, with half of them presenting with an exacerbation of their underlying neurological disease. The neurological symptoms developed at a median of 2 days after the onset of systemic symptoms. The median length of hospital stay was 3 days, and 79 % were monitored in general wards. Neurologic complications associated with the novel influenza A (H1N1) 2009 strain were generally mild and had a good outcome. They occurred more frequently in patients with underlying neurological disorders. Seizures and encephalopathy were the most common manifestations, similar to other influenza virus strains.

Sport talent identification and development (TI and TD) in youth continues to attract strong interest among coaches, sport scientists and sport administrators. TI for sport in youth with the anticipation of future elite level sport achievement is both an art and a science, and is strongly influenced by within athlete and extraneous-to-athlete factors (ecosystem of support or the lack of). The returns from investment on current TI and TD models of sport in youth are subpar in that few continue in the sport to achieve podium positions at the elite sport level in adulthood. Why, where and how one succeeds in sport, and what that success means to the athlete and stakeholders are dependent on the culture and context of the country. We advocate harnessing the power of sport to help in youth development, to be holistic in its nurturance, to allow for individual idiosyncratic expressions of the athletes, to provide for talent transfer across sport, and to facilitate key stakeholders to 'join' hands to work for the common interest and understanding for as many youth and adults so as to provide them with opportunities through support and coaching to compete at the different levels of competition in sport. Governments, policy makers and administrators of sport must decide, within their specific circumstances, if TI and TD in sport in youth is serving a meaningful purpose and is a viable return on investment; in short, is it mission possible or is it… a quest for the Holy Grail for a podium finish in elite level sport competition?, (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

We conducted a 2-year multicentre prospective observational study to determine the epidemiology of and mortality associated with invasive fungal diseases (IFDs) among patients with haematological disorders in Asia. Eleven institutions from 8 countries/regions participated, with 412 subjects (28.2% possible, 38.3% probable and 33.5% proven IFDs) recruited. The epidemiology of IFDs in participating institutions was similar to Western centres, with Aspergillus spp. (65.9%) or Candida spp. (26.7%) causing the majority of probable and proven IFDs. The overall 30-day mortality was 22.1%. Progressive haematological disorder (odds ratio [OR] 5.192), invasive candidiasis (OR 3.679), and chronic renal disease (OR 6.677) were independently associated with mortality., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Controlled release plays an essential role in formulating topical and transdermal drug delivery systems. In this study, we correlated the skin permeation of Sesamin, a lipophilic drug, with the rheological properties of two different organogel carriers, i.e., low molecular weight gelling agent N-lauroyl-l-glutamic acid di-n-butylamide (GP-1) and Carbopol polymeric gels. Although these two gels have distinct network structures, they share the same trend: the more rigid the gel network and the higher the gelator concentration, the lower the steady flux of Sesamin through skin. This negative correlation lies in the fact that organogel network hinders the diffusion of drug to the gel-skin interface; as a result, the depletion zone near the interface is non-negligible and contributes to the resistance of the whole diffusion system, and thus, the permeation flux is reduced. More interestingly, the dependence of the steady flux against gel complex modulus at the linear viscoelastic region followed a "universal" power law regardless of the gel types, i.e., 1/J = 1/J0 + a(G*)(ε)/C0 with a = 11.25, ε = 0.21 ± 0.03 for GP-1 gels, and a = 0.16, ε = 1.05 ± 0.06 for Carbopol gels, J0 is the steady flux without gel (G* = 0), and C0 is the initial concentration of drug in gels. The empirical formulae are crucial in developing transdermal organogel systems with controlled release of drug content through readily obtainable data of their rheological properties. The explanation for the power law dependence of the steady flux on gel complex modulus is discussed.

We aim to study the association between hyperglycemia and in-hospital outcomes among children with moderate and severe traumatic brain injury (TBI). This retrospective cohort study was conducted in a tertiary pediatric hospital between 2003 and 2013. All patients < 16 years old who presented to the Emergency Department within 24 hours of head injury with a Glasgow Coma Scale (GCS) ≤ 13 were included. Our outcomes of interest were death, 14 ventilation-free, 14 pediatric intensive care unit- (PICU-) free, and 28 hospital-free days. Hyperglycemia was defined as glucose > 200 mg/dL (11.1 mmol/L). Among the 44 patients analyzed, the median age was 8.6 years (interquartile range (IQR) 5.0-11.0). Median GCS and pediatric trauma scores were 7 (IQR 4-10) and 4 (IQR 3-6), respectively. Initial hyperglycemia was associated with death (37% in the hyperglycemia group versus 8% in the normoglycemia group, p = 0.019), reduced median PICU-free days (6 days versus 11 days, p = 0.006), and reduced median ventilation-free days (8 days versus 12 days, p = 0.008). This association was however not significant in the stratified analysis of patients with GCS ≤ 8. Conclusion. Our findings demonstrate that early hyperglycemia is associated with increased mortality, prolonged duration of mechanical ventilation, and PICU stay in children with TBI.

Introduction: Bacterial infections are major causes of early morbidity and mortality after liver transplantation. Selective digestive decontamination (SDD) can be used pre-operatively for living-donor liver transplant (LD-LT), but its role in this setting remains controversial., Methods: To evaluate this strategy, we retrospectively analyzed a cohort of consecutive LD-LTs performed in our center from March 2007 to February 2011 and compared the incidence and nature of early infectious complications, length of intensive care unit stay and hospitalization, antibiotic use, and emergence of resistant bacteria in patients with or without SDD prophylaxis., Results: Of 148 LD-LTs in the study period, 111 received SDD prophylaxis while 37 did not. In a multivariate model, the independent factors associated with an increased risk of early post-transplant infections were length of postoperative mechanical ventilation (for every additional day odds ratio [OR] = 2.37, 95% confidence interval [CI] 1.4-4.0; P = 0.002), and choledochojejunostomy (OR = 4.5, 95% CI 1.95-10.5; P < 0.001). Use of SDD did not affect the rate or distribution of infectious complications, duration of hospitalization, antibiotic use, or acquisition of resistant bacteria (OR = 3.52, 95% CI 0.43-15.17; P = 0.376)., Conclusion: In conclusion, the use of SDD prophylaxis in LD-LT was not beneficial and should be avoided, as it offers no advantage and could potentiate the emergence of multidrug-resistant organisms., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Ventricular enlargement is a common finding after severe head injury and has a poor prognosis if associated with post-traumatic hydrocephalus (PTH). We retrospectively reviewed our head injury database and identified patients who suffered from severe head injury and subsequently had shunt insertion after a diagnosis of PTH. A total of 871 patients with severe head injury were admitted from April 1999 to December 2006. Twenty-three patients (2.6%) were diagnosed with post-traumatic hydrocephalus and had a shunt inserted. Multiple logistic regression analysis showed that age, and unilateral and bilateral decompressive craniectomy, were significant predictors of PTH. The timing of shunt placement was between 2 weeks and 5 months post-head injury with a mean interval of 70 days. Three patients developed complications after shunt insertion. Seventeen patients (74%) achieved improvement after shunt insertion while the remainder had no significant change in neurological status. Eleven patients (48%) had improvements in their Glasgow Coma Scale (GCS) score of ≥2 points, while six patients (26%) had a single-point improvement in their GCS score. At 1 year after shunting, 35% of patients had Glasgow Outcome Scale scores of 3 to 4. PTH is a condition that has an insidious onset with varying clinical and radiological presentations. The incidence is low but there is a significant benefit from ventricular shunt insertion. The use of cerebrospinal fluid dynamic studies, in addition to clinical and radiological findings, has the potential for better diagnosis and management of these patients., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Human parainfluenza virus (HPIV) infection as an aetiology of acute viral myocarditis is rare, with only few cases reported in the literature to date. Here we report a case of fulminant HPIV-2 myocarditis in a 47 year-old man with viraemia who was successfully treated with intravenous ribavirin and intravenous immunoglobulin (IVIG). There are currently no recommendations on the treatment of HPIV myocarditis. We are, to our knowledge, the first to report a patient with a documented HPIV-2 viraemia that subsequently cleared after the initiation of antiviral therapy. Although it is difficult to definitively attribute the patient's clinical improvement to ribavirin or IVIG alone, our case does suggest that clinicians may wish to consider initiating ribavirin and IVIG in patients with HPIV myocarditis and persistent viraemia not responding to supportive measures alone., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Acute kidney injury (AKI) is a complication of severe malaria, and rhabdomyolysis with myoglobinuria is an uncommon cause. We report an unusual case of severe falciparum malaria with dengue coinfection complicated by AKI due to myoglobinemia and myoglobinuria while maintaining a normal creatine kinase (CK)., Case Presentation: A 49-year old Indonesian man presented with fever, chills, and rigors with generalized myalgia and was diagnosed with falciparum malaria based on a positive blood smear. This was complicated by rhabdomyolysis with raised serum and urine myoglobin but normal CK. Despite rapid clearance of the parasitemia with intravenous artesunate and aggressive hydration maintaining good urine output, his myoglobinuria and acidosis worsened, progressing to uremia requiring renal replacement therapy. High-flux hemodiafiltration effectively cleared his serum and urine myoglobin with recovery of renal function. Further evaluation revealed evidence of dengue coinfection and past infection with murine typhus., Conclusion: In patients with severe falciparum malaria, the absence of raised CK alone does not exclude a diagnosis of rhabdomyolysis. Raised serum and urine myoglobin levels could lead to AKI and should be monitored. In the event of myoglobin-induced AKI requiring dialysis, clinicians may consider using high-flux hemodiafiltration instead of conventional hemodialysis for more effective myoglobin removal. In Southeast Asia, potential endemic coinfections that can also cause or worsen rhabdomyolysis, such as dengue, rickettsiosis and leptospirosis, should be considered.

This study examines the effects of Ramadan fasting on performance during an intense exercise session performed at three different times of the day, i.e., 08:00, 18:00, and 21:00 h. The purpose was to determine the optimal time of the day to perform an acute high-intensity interval exercise during the Ramadan fasting month. After familiarization, nine trained athletes performed six 30-s Wingate anaerobic test (WAnT) cycle bouts followed by a time-to-exhaustion (T(exh)) cycle on six separate randomized and counterbalanced occasions. The three time-of-day nonfasting (control, CON) exercise sessions were performed before the Ramadan month, and the three corresponding time-of-day Ramadan fasting (RAM) exercise sessions were performed during the Ramadan month. Note that the 21:00 h session during Ramadan month was conducted in the nonfasted state after the breaking of the day's fast. Total work (TW) completed during the six WAnT bouts was significantly lower during RAM compared to CON for the 08:00 and 18:00 h (p < .017; effect size [d] = .55 [small] and .39 [small], respectively) sessions, but not for the 21:00 h (p = .03, d = .18 [trivial]) session. The T(exh) cycle duration was significantly shorter during RAM than CON in the 18:00 (p < .017, d = .93 [moderate]) session, but not in the 08:00 (p = .03, d = .57 [small]) and 21:00 h (p = .96, d = .02 [trivial]) sessions. In conclusion, Ramadan fasting had a small to moderate, negative impact on quality of performance during an acute high-intensity exercise session, particularly during the period of the daytime fast. The optimal time to conduct an acute high-intensity exercise session during the Ramadan fasting month is in the evening, after the breaking of the day's fast.

This was a multicenter, blinded, Phase II study (NCT00880893) conducted in Singapore. The primary objectives were to evaluate the safety of a tetravalent dengue vaccine (TDV) comprising four recombinant, live, attenuated viruses (CYD-TDV) and the dengue virus serotype-specific antibody responses before and 28 d after each vaccination. Participants were randomized 3:1 to receive three doses of CYD-TDV or a control vaccine at 0, 6 and 12 mo. Control vaccine was placebo for the first dose (all ages) and for subsequent doses, licensed hepatitis-A for children (aged 2-11 y) or influenza vaccine for adolescents (12-17 y) and adults (18-45 y). Between April and October 2009, 317 children, 187 adolescents and 696 adults were enrolled. In all age groups, reactogenicity was higher after the first injection of CYD-TDV than after placebo control. Reactogenicity after subsequent CYD-TDV doses was no higher than after the first dose, and tended to be lower or similar to that seen after active control vaccination. Seropositivity rates and geometric mean neutralizing antibody titers (GMTs; 1/dil) against all four dengue virus serotypes increased in all age groups after each of the three CYD-TDV doses. Post-dose 3, 66.5% of all participants were seropositive to all four serotypes, and 87.2% were seropositive to ≥ 3 serotypes; GMTs for all participants ranged from 43.0 against dengue virus serotype 1 to 100 against dengue virus serotype 4. GMTs were higher in children than in adolescents. These results support the continued development of CYD-TDV for the prevention of dengue disease.

Invasive fungal infections are infections of importance and are increasing in incidence in immunocompromised hosts such as patients who have had hematopoietic stem cell and solid organ transplants. Despite our expanded antifungal armamentarium, these infections cause considerable morbidity and mortality. Indeed, certain trends have emerged in these invasive fungal infections: a rise in the incidence of invasive mold infections, an increase in the non-albicans strains of Candida spp. causing invasive disease and, finally, the emergence of less susceptible fungal strains that are resistant to the broader-spectrum antifungal agents due to overutilization of these agents. Clinicians must recognize the patient groups that are potentially at risk for these invasive fungal infections, as well as the risk factors for such infections. By using more sensitive nonculture-based diagnostic techniques, appropriate therapy may be initiated earlier to enhance survival in these immunocompromised patient populations.

Background: Influenza can produce significant complications in immunocompromised persons., Methods: We studied the effects of the pandemic (H1N1) 2009 (pH1N1) infection on solid organ transplant recipients in our hospital, with emphasis on clinical information, duration of viral culture positivity, polymerase chain reaction positivity, effects of oseltamivir therapy, and graft status at 6 months of follow-up., Results: Twenty-two cases of pH1N1 infection involving 18 renal, two lung, one heart, and one liver transplant recipients were seen from July 14 to September 8, 2009. Their median age was 50.5 years (range 20-70 years); 64% were women, and median time posttransplant was 40 months (range 6-204 months). Common symptoms were fever (86%), cough (77%), sore throat (55%), phlegm (32%), and myalgia (27%). The median duration of symptoms (n=21) and duration of polymerase chain reaction positivity (n=15) were 7 (range 4-13 days) and 8 days (range 4-16 days), respectively. Mean (± SD) duration of symptom resolution (7.4 ± 3.0 vs. 7.8 ± 3.0 days, P=0.76) and viral culture positivity (5.3 ± 2.8 vs. 4.3 ± 3.2 days, P=0.65) did not differ between those who received a 5-day (n=9) or 10-day (n=12) course of oseltamivir. Five patients (22.7%) developed pneumonia with three needing intensive care. Mortality rate was 4.5% (1/22). At 6 months, three graft rejections involving two renal and one lung developed., Conclusions: Our findings indicate that the pH1N1 infection in solid organ transplant recipients is associated with some degree of morbidity and may affect the function of the transplanted organ. In this nonrandomized comparison, patients treated with 5 days of oseltamivir did not fare worse compared with those who received 10 days.

Introduction: The influenza pandemic has generated much interest in the press and the medical world. We report our experience with 15 cases of severe novel influenza A H1N1 (2009) infections requiring intensive care. The aim of this review is to improve our preparedness for epidemics and pandemics by studying the most severely affected patients., Clinical Picture: During the epidemic, hospitals were required to provide data on all confirmed H1N1 cases admitted to an intensive care unit (ICU) to the Ministry of Health. We abstracted information from this dataset for this report. To highlight learning points, we reviewed the case notes of, and report, the fi ve most instructive cases., Treatment: There were 15 cases admitted to an ICU from July 4, 2009 to August 30, 2009. Two patients died., Conclusions: The lessons we wish to share include the following: preparedness should include having intermediate-care facilities that also provide single room isolation and skilled nursing abilities, stringent visitor screening should be implemented and influenza may trigger an acute myocardial infarction in persons with risk factors.