Prognostic values of a combination of intervals between respiratory illness and onset of neurological symptoms and elevated serum IgM titers in Mycoplasma pneumoniae encephalopathy

Background/PurposeTo retrospectively analyze the clinical manifestations of Mycoplasma pneumoniae (M. pneumoniae)-associated encephalopathy in pediatric patients.MethodsPediatric patients with positive serum anti-M. pneumoniae immunoglobulin M (IgM) were enrolled in this study. Clinical signs and symptoms, laboratory data, neuroimaging findings, and electrophysiological data were reviewed.ResultsOf 1000 patients identified, 11 (1.1%; male:female ratio = 7:4) had encephalopathy and were admitted to the pediatric intensive care unit. Clinical presentation included fever, symptoms of respiratory illness, and gastrointestinal upset. Neurological symptoms included altered consciousness, seizures, coma, focal neurological signs, and personality change. Neuroimaging and electroencephalographic findings were non-specific. Specimens of cerebrospinal fluid (CSF) for M. pneumoniae polymerase chain reaction (PCR) were negative. Higher M. pneumoniae IgM titers and longer intervals between respiratory and CNS manifestations were associated with worse outcomes.ConclusionClinical manifestations of M. pneumoniae-associated encephalopathy were variable. Diagnosis of M. pneumoniae encephalopathy should not rely on CSF detection of M. pneumoniae by PCR. M. pneumoniae IgM titers and intervals between respiratory and CNS manifestations might be possibly related to the prognosis of patients with M. pneumoniae-associated encephalopathy

Predicting serum levels of lithium-treated patients: A supervised machine learning approach

Routine monitoring of lithium levels is common clinical practice. This is because the lithium prediction strategies available developed by previous studies are still limited due to insufficient prediction performance. Thus, we used machine learning approaches to predict lithium concentration in a large real-world dataset. Real-world data from multicenter electronic medical records were used in different machine learning algorithms to predict: (1) whether the serum level was 0.6-1.2 mmol/L or 0.0-0.6 mmol/L (binary prediction), and (2) its concentration value (continuous prediction). We developed models from 1505 samples through 5-fold cross-validation and used 204 independent samples to test their performance by evaluating their accuracy. Moreover, we ranked the most important clinical features in different models and reconstructed three reduced models with fewer clinical features. For binary and continuous predictions, the average accuracy of these models was 0.70-0.73 and 0.68-0.75, respectively. Seven features were listed as important features related to serum lithium levels of 0.6-1.2 mmol/L or higher lithium concentration, namely older age, lower systolic blood pressure, higher daily and last doses of lithium prescription, concomitant psychotropic drugs with valproic acid and -pine drugs, and comorbid substance-related disorders. After reducing the features in the three new predictive models, the binary or continuous models still had an average accuracy of 0.67-0.74. Machine learning processes complex clinical data and provides a potential tool for predicting lithium concentration. This may help in clinical decision-making and reduce the frequency of serum level monitoring

A Distributed Urban Traffic Congestion Prevention Mechanism for Mixed Flow of Human-Driven and Autonomous Electric Vehicles

Traffic congestion in urban areas has become a critical problem that municipal governments cannot overlook. Meanwhile, mixed traffic systems containing both autonomous and human-driven electric vehicles ramp up the challenge for traffic management in urban areas. Although numerous researchers have proposed traffic control heuristics to alleviate traffic congestion problems in the recent literature, scant research has addressed the joint problems of route and charging strategies for electric vehicles along with urban traffic congestion prevention. Accordingly, this work tackles the complex task of traffic management in urban areas during peak periods by using practical congestion prevention strategies that consider the characteristics of mixed traffic flows and the charging demands of electric vehicle users. Notably, we apply support vector regressions to compute the charging time at each charging point and the traverse time of an electric vehicle at each road segment/intersection, based on historical traffic data. The simulation results reveal that the proposed algorithms are feasible because they can avoid possible occurrences of traffic congestion during rush hours and provide the routes and charging options that are chosen by electric vehicle users

Transmission of acute infectious illness among cases of Kawasaki disease and their household members

Background/purposeKawasaki disease (KD) is a disease of unknown cause and the causative agent is most likely to be infectious in nature. To investigate the household transmission pattern of infectious illness and etiology, we thus initiated a prospective case and household study.MethodsWe enrolled KD cases and their household members from February 2004 to September 2008. The KD cases and their household members accepted questionnaire-based interviews of the contact history, signs of infection, and symptoms to check whether clusters of infectious illness occurred.ResultsA total of 142 KD cases and 561 household members were enrolled. Among the 142 KD cases, 136 cases (96%) were typical KD, and six (4%) were atypical KD. Of the 561 household members, 17% were siblings, 46% were parents, 18% were grandparents, and the others were cousins or babysitters. Prior to the onset of their KD illness, 66% (94/142) KD cases had contact with ill household members. On the same day of the onset of KD cases' illness, 4% (6/142) KD cases had household members with illness. After KD cases' disease onset, 70% (100/142) KD cases had at least one other family member with illness. Overall, 61% (343/561) of all the household members had acute infectious illness during KD cases' acute stage, and 92% (130/142) of the families had clusters of infectious illness.ConclusionA total of 66% KD cases had positive contact with ill household members prior to their disease onset and 92% of families had clusters of infectious illness, so KD is strongly associated with infections

A Macroporous TiO2 Oxygen Sensor Fabricated Using Anodic Aluminium Oxide as an Etching Mask

An innovative fabrication method to produce a macroporous Si surface by employing an anodic aluminium oxide (AAO) nanopore array layer as an etching template is presented. Combining AAO with a reactive ion etching (RIE) processes, a homogeneous and macroporous silicon surface can be effectively configured by modulating AAO process parameters and alumina film thickness, thus hopefully replacing conventional photolithography and electrochemical etch methods. The hybrid process integration is considered fully CMOS compatible thanks to the low-temperature AAO and CMOS processes. The gas-sensing characteristics of 50 nm TiO2 nanofilms deposited on the macroporous surface are compared with those of conventional plain (or non-porous) nanofilms to verify reduced response noise and improved sensitivity as a result of their macroporosity. Our experimental results reveal that macroporous geometry of the TiO2 chemoresistive gas sensor demonstrates 2-fold higher (∼33%) improved sensitivity than a non-porous sensor at different levels of oxygen exposure. In addition, the macroporous device exhibits excellent discrimination capability and significantly lessened response noise at 500 °C. Experimental results indicate that the hybrid process of such miniature and macroporous devices are compatible as well as applicable to integrated next generation bio-chemical sensors

Household secondhand smoke exposure of elementary schoolchildren in Southern Taiwan and factors associated with their confidence in avoiding exposure: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Exposure to household Secondhand Smoke (SHS) poses a major health threat to children after an indoor smoking ban was imposed in Taiwan. This study aimed to assess the household SHS exposure in elementary school children in southern Taiwan and the factors associated with their avoidance of SHS exposure before and after the implementation of Taiwan's new Tobacco Hazards Prevention Act in 2009.</p> <p>Methods</p> <p>In this cross-sectional school-based study, data on household SHS exposure, avoidance of SHS and related variables was obtained from the 2008 and 2009 Control of School-aged Children Smoking Study Survey. A random sample of 52 elementary schools was included. A total of 4450 3-6 graders (aged 8-13) completed the questionnaire. Regression models analyzed factors of children's self-confidence to avoid household SHS exposure.</p> <p>Results</p> <p>Over 50% of children were found to have lived with a family member who smoked in front of them after the new law enacted, and 35% of them were exposed to household SHS more than 4 days a week. Having a positive attitude toward smoking (β = -0.05 to -0.06) and high household SHS exposure (β = -0.34 to -0.47) were significantly associated with a lower avoidance of SHS exposure. Comparing to girls, boys had lower scores in their knowledge of tobacco hazards; and this factor was significantly related to their SHS avoidance (β = 0.13-0.14).</p> <p>Conclusions</p> <p>The intervention program should enhance school children do actively avoid exposure to SHS in home settings, and more importantly, provide tobacco hazard knowledge to male students to avoid exposure to household SHS for themselves. The results also provide further evidence that Tobacco Hazards Prevention Act should perhaps be extended to the family environment in order to protect children from the hazards of household SHS exposure.</p

Emulsified Nanoparticles Containing Inactivated Influenza Virus and CpG Oligodeoxynucleotides Critically Influences the Host Immune Responses in Mice

Antigen sparing and cross-protective immunity are regarded as crucial in pandemic influenza vaccine development. Both targets can be achieved by adjuvantation strategy to elicit a robust and broadened immune response. We assessed the immunogenicity of an inactivated H5N1 whole-virion vaccine (A/Vietnam/1194/2004 NIBRG-14, clade 1) formulated with emulsified nanoparticles and investigated whether it can induce cross-clade protecting immunity.After formulation with PELC, a proprietary water-in-oil-in-water nanoemulsion comprising of bioresorbable polymer/Span(R)85/squalene, inactivated virus was intramuscularly administered to mice in either one-dose or two-dose schedule. We found that the antigen-specific serum antibody responses elicited after two doses of non-adjuvanted vaccine were lower than those observed after a single dose of adjuvanted vaccine, PELC and the conventional alum adjuvant as well. Moreover, 5 microg HA of PELC-formulated inactivated virus were capable of inducing higher antibodies than those obtained from alum-adjuvanted vaccine. In single-dose study, we found that encapsulating inactivated virus into emulsified PELC nanoparticles could induce better antibody responses than those formulated with PELC-adsorbed vaccine. However, the potency was rather reduced when the inactivated virus and CpG (an immunostimulatory oligodeoxynucleotide containing unmethylated cytosine-guanosine motifs) were co-encapsulated within the emulsion. Finally, the mice who received PELC/CpG(adsorption)-vaccine could easily and quickly reach 100% of seroprotection against a homologous virus strain and effective cross-protection against a heterologous virus strain (A/Whooper swan/Mongolia/244/2005, clade 2.2).Encapsulating inactivated H5N1 influenza virus and CpG into emulsified nanoparticles critically influences the humoral responses against pandemic influenza. These results demonstrated that the use of PELC could be as antigen-sparing in preparation for a potential shortage of prophylactic vaccines against local infectious diseases, in particular pandemic influenza. Moreover, the cross-clade neutralizing antibody responses data verify the potential of such adjuvanted H5N1 candidate vaccine as an effective tool in pre-pandemic preparedness

Production of Inactivated Influenza H5N1 Vaccines from MDCK Cells in Serum-Free Medium

BACKGROUND: Highly pathogenic influenza viruses pose a constant threat which could lead to a global pandemic. Vaccination remains the principal measure to reduce morbidity and mortality from such pandemics. The availability and surging demand for pandemic vaccines needs to be addressed in the preparedness plans. This study presents an improved high-yield manufacturing process for the inactivated influenza H5N1 vaccines using Madin-Darby canine kidney (MDCK) cells grown in a serum-free (SF) medium microcarrier cell culture system. PRINCIPAL FINDING: The current study has evaluated the performance of cell adaptation switched from serum-containing (SC) medium to several commercial SF media. The selected SF medium was further evaluated in various bioreactor culture systems for process scale-up evaluation. No significant difference was found in the cell growth in different sizes of bioreactors studied. In the 7.5 L bioreactor runs, the cell concentration reached to 2.3 × 10(6) cells/mL after 5 days. The maximum virus titers of 1024 Hemagglutinin (HA) units/50 µL and 7.1 ± 0.3 × 10(8) pfu/mL were obtained after 3 days infection. The concentration of HA antigen as determined by SRID was found to be 14.1 µg/mL which was higher than those obtained from the SC medium. A mouse immunogenicity study showed that the formalin-inactivated purified SF vaccine candidate formulated with alum adjuvant could induce protective level of virus neutralization titers similar to those obtained from the SC medium. In addition, the H5N1 viruses produced from either SC or SF media showed the same antigenic reactivity with the NIBRG14 standard antisera. CONCLUSIONS: The advantages of this SF cell-based manufacturing process could reduce the animal serum contamination, the cost and lot-to-lot variation of SC medium production. This study provides useful information to manufacturers that are planning to use SF medium for cell-based influenza vaccine production

Understanding Sensory Nerve Mechanotransduction through Localized Elastomeric Matrix Control

BACKGROUND: While neural systems are known to respond to chemical and electrical stimulation, the effect of mechanics on these highly sensitive cells is still not well understood. The ability to examine the effects of mechanics on these cells is limited by existing approaches, although their overall response is intimately tied to cell-matrix interactions. Here, we offer a novel method, which we used to investigate stretch-activated mechanotransduction on nerve terminals of sensory neurons through an elastomeric interface. METHODOLOGY/PRINCIPAL FINDINGS: To apply mechanical force on neurites, we cultured dorsal root ganglion neurons on an elastic substrate, polydimethylsiloxane (PDMS), coated with extracellular matrices (ECM). We then implemented a controlled indentation scheme using a glass pipette to mechanically stimulate individual neurites that were adjacent to the pipette. We used whole-cell patch clamping to record the stretch-activated action potentials on the soma of the single neurites to determine the mechanotransduction-based response. When we imposed specific mechanical force through the ECM, we noted a significant neuronal action potential response. Furthermore, because the mechanotransduction cascade is known to be directly affected by the cytoskeleton, we investigated the cell structure and its effects. When we disrupted microtubules and actin filaments with nocodozale or cytochalasin-D, respectively, the mechanically induced action potential was abrogated. In contrast, when using blockers of channels such as TRP, ASIC, and stretch-activated channels while mechanically stimulating the cells, we observed almost no change in action potential signalling when compared with mechanical activation of unmodified cells. CONCLUSIONS/SIGNIFICANCE: These results suggest that sensory nerve terminals have a specific mechanosensitive response that is related to cell architecture