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Antipsychotic drugs (APDs) are the first-line pharmacological treatments for schizophrenia. Recent human studies have found that myelin integrity could be improved by APD treatment in schizophrenia patients. Previous studies indicated that regulation of oligodendrocyte development and function may be a novel target for APDs.
Aims:
The aim of this current study was to examine the possible effects of the antipsychotic drugs (APDs) haloperidol (HAL), olanzapine (OLA), and quetiapine (QUE) on the development of oligodendroglial lineage cells.
Main methods:
CG4 cells, an oligodendrocyte progenitor cell line, were treated with various concentrations of HAL, OLA, or QUE for specific periods. The proliferation and differentiation of the CG4 cells were measured. The regulation of CG4 cell differentiation by oligodendrocyte lineage transcription factors 1 and 2 (Olig1 and Olig2) was examined.
Results:
The APDs used in this study had no effect on the proliferation of CG4 cells. The APDs elevated the expression of 2’,3’-cyclic nucleotide 3’-phosphodiesterase (CNP), a specific marker of oligodendrocytes, and promoted the CG4 cells to differentiate into CNP positive oligodendrocytes. QUE and OLA increased the expression of Olig1 and Olig2 whereas HAL only increased the expression of Olig2.
Conclusions:
Our findings suggest that oligodendrocyte development is a target of HAL, OLA, and QUE and provide further evidence of the important role of oligodendrocytes in the pathophysiology and treatment of schizophrenia. They also indicate that the expression level of oligodendrocyte/myelinrelated genes could be profoundly affected by APDs.
Hand-foot-mouth disease (HFMD) is an acute infectious disease caused by serotypes of the enterovirus (EV) family. HFMD reinfection occurs commonly in lack of cross-protection between different EV serotypes. In this study, we investigated the hazards of HFMD reinfection using Cox-proportional hazard model. Retrospective data of 95 209 HFMD cases in Wuhan during 2008–2015 was used. Kaplan–Meier survival methods and Cox-proportional hazard model were used to estimate the hazard probabilities. Of the all HFMD cases, about 2% experienced reinfection (1842/95 209). Kaplan–Meier curves revealed the reinfection risk sharply increased before 40 months from first infection. Higher hazards of reinfection were detected among those who were males, aged 3 years and below, scattered children, belonging to urban areas and first infected with coxsackievirus (CV)-A16 compared with their respective counterparts. Cox-proportional hazard model suggested that gender, age, group, living area and serotypes of first infection had significant effect on reinfection even after adjusting for potential confounding effects of other selected factors considered in the study. These results indicate that boys aged 3 years and below, especially those living in urban areas and first infected with CV-A16 are more prone to reinfection. Interventions should be imposed on these high-risk populations.
Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.
In this study, we investigated thermotolerance, several physiological responses and damage to reproductive cells in chlorpyrifos-resistant (Rc) and -susceptible (Sm) strains of the diamondback moth, Plutella xylostella subjected to heat stress. The chlorpyrifos resistance of these strains was mediated by a modified acetylcholinesterase encoded by an allele, ace1R, of the ace1 gene. Adults of the Rc strain were less heat resistant than those of the Sm strain; they also had lower levels of enzymatic activity against oxidative damage, higher reactive oxygen species contents, weaker upregulation of two heat shock protein (hsp) genes (hsp69s and hsp20), and stronger upregulation of two apoptotic genes (caspase-7 and -9). The damage to sperm and ovary cells was greater in Rc adults than in Sm adults and was temperature sensitive. The lower fitness of the resistant strain, compared with the susceptible strain, is probably due to higher levels of oxidative stress and apoptosis, which also have deleterious effects on several life history traits. The greater injury observed in conditions of heat stress may be due to both the stronger upregulation of caspase genes and weaker upregulation of hsp genes in resistant than in susceptible individuals.
The West African 2014 Ebola outbreak has highlighted the need for a better information network. Hybrid information networks, an integration of both hierarchical and formalized command control-driven and community-based, or ad hoc emerging networks, could assist in improving public health responses. By filling the missing gaps with social media use, the public health response could be more proactive rather than reactive in responding to such an outbreak of global concern. This article provides a review of the current social media use specifically in this outbreak by systematically collecting data from ProQuest Newsstand, Dow Jones Factiva, Program for Monitoring Emerging Diseases (ProMED) as well as Google Trends. The period studied is from 19 March 2014 (first request for information on ProMED) to 15 October 2014, a total of 31 weeks. The term ‘Ebola’ was used in the search for media reports. The outcome of the review shows positive results for social media use in effective surveillance response mechanisms – for improving the detection, preparedness and response of the outbreak – as a complement to traditional, filed, work-based surveillance approach.
We derive zphot for sources in the entire (~0.4 deg2) H-HDF-N field with the EAzY code, based on PSF-matched broad-band (U band to IRAC 4.5 μm) photometry. Our catalog consists of a total of 131,678 sources. We find σNMAD = 0.029 for non-X-ray sources. We also classify each object as a star or galaxy through SED fitting. Furthermore, we match our catalog with the 2 Ms CDF-N main X-ray catalog. For the 462 matched non-stellar X-ray sources, we improve their zphot quality (σNMAD = 0.035) by adding three additional AGN templates. We make our photometry and zphot catalog publicly available.
The impact of vanB vancomycin-resistant enterococci (VRE) bacteraemia on length of stay (LOS) in hospital, after adjusting for the time-varying nature of enterococcal bacteraemia (variable onset of bacteraemia post-admission), is unknown. Survival analyses (time-varying Cox and competing risks regression) were performed on vanB VRE bacteraemia patients, matched 1:1 with vancomycin-susceptible enterococci bacteraemia patients to determine the factors associated with LOS in these patients. In Cox regression analysis, vanB VRE bacteraemia, intensive-care-unit admission, Charlson co-morbidity index score ⩾4, and an increase in the time to receive appropriate antibiotics were associated with prolonged LOS. Competing risks regression which accounts for the influence of in-patient mortality on the ability to observe the event discharge alive from hospital suggests that, vanB VRE bacteraemia was not significantly associated with prolonged LOS. For the first time, the rate of discharge from hospital in patients with vanB VRE bacteraemia has been quantified.
A radio-frequency magnetron sputtering technique and subsequent rapid thermal annealing (RTA) at 600, 700, 800, and 900 °C were implemented to grow high-quality Ga-doped MgxZn1-xO (GMZO) epi-layers. The GMZO films were deposited using a radio-frequency magnetron sputtering system and a 4 inch ZnO/MgO/Ga2O3 (75/20/5 wt %) target. The Hall results, X-ray diffraction (XRD), and transmittance were determined and are reported in this paper. The Hall results indicated that the increase in mobility was likely caused by the improved crystallization in the GMZO films after thermal annealing. The XRD results revealed that MgxZn1-xO (111) and MgO2 (200) peaks were obtained in the GMZO films. The absorption edges of the as-grown and annealed GMZO films shifted toward the short wavelength of 373 nm at a transmittance of 90%. According to these results, GMZO films are feasible for forming transparent contact layers for near-ultraviolet light-emitting diodes.
We investigated the seasonality of tuberculosis (TB) in Wuhan, China, to evaluate the increased risk of disease transmission during each season and to develop an effective TB control strategy. We applied spectral analysis to the weekly prevalence data of sputum smear positive (SSP) and sputum smear negative (SSN) pulmonary TB reported from 2006 to 2010. Cases of both SSP and SSN feature 1·0- and 0·5-year periodic modes. The least squares method was used to fit curves to the two periodic modes for SSP and SSN data. The curves demonstrated dominant peaks in spring similar to cases reported previously for other locations. Notably for SSP, dominant peaks were also observed in summer. The spring peaks of SSP and SSN were explained in terms of poorly ventilated and humid rooms and vitamin D deficiency. For the summer peaks of SSP, summer influenza epidemics in Wuhan may contribute to the increase in TB prevalence.
We propose the spot-size effect in laser-induced damage to optical thin films as a method to investigate the defect removal model which is one of the laser conditioning mechanisms, and the theoretical and experimental studies are presented. A standard deviation σ2 is set up for fitting the damage thresholds which are obtained by multi-spot size test. The laser conditioning effect on ZrO2/SiO2 multilayer high reflective films is analyzed through this application. It is found that the mean distance of two initiating defects is increased by laser conditioning, which means that the defect density is decreased. Thus, the initiating defects are removed partially by laser conditioning. Furthermore, the intrinsic damage threshold of the film is little affected through the laser conditioning process.
Viral hepatitis is recognized as one of the most frequently reported diseases, and especially in China, acute and chronic liver disease due to viral hepatitis has been a major public health problem. The present study aimed to analyse and predict surveillance data of infections of hepatitis A, B, C and E in Wuhan, China, by the method of time-series analysis (MemCalc, Suwa-Trast, Japan). On the basis of spectral analysis, fundamental modes explaining the underlying variation of the data for the years 2004–2008 were assigned. The model was calculated using the fundamental modes and the underlying variation of the data reproduced well. An extension of the model to the year 2009 could predict the data quantitatively. Our study suggests that the present method will allow us to model the temporal pattern of epidemics of viral hepatitis much more effectively than using the artificial neural network, which has been used previously.
This article presents a study on elastic anisotropy of Cu by indentations at different penetration depth ranges (sub-10 nm, several-10 nm, and several-100 nm), and the impact of elastic anisotropy on the stress in 3D stacked integrated circuits (3D ICs). The reduced modulus, ER, values determined at sub-10 nm indentations on Cu single crystals are very close to the unidirectional values. Similarly, cross-sectional sub-10 nm indentation tests on the Cu grains in a through-silicon via (TSV) show unidirectional ER values. In contrast, the Hill’s average values are observed at several-100 nm indentations. We propose that before lattice rotation happens within a volume beneath the indentation, elastic anisotropy can be strongly reflected in the ER value. When the experimentally measured Cu elastic anisotropy is used in a technology computer-aided design simulation of a Cu-filled TSV, significant impacts are observed on the stress field and the carrier mobility variation in an active Si region.
The 2009 novel H1N1 influenza pandemic had a significant impact on Shenzhen's population with 2063 laboratory-confirmed human H1N1 cases and five deaths being reported. We used parameters from two population-based surveys and the Shenzhen Influenza Surveillance System to estimate the total number of H1N1 influenza infections in Shenzhen in the 2009 pandemic. The attack rate of influenza-like illness (ILI) in family households was 11·2% (95% CI 9·4–13·0), with 80·2% (95% CI 77·8–82·5) seeking medical care. The ILI attack rate in workers was 38·1% (95% CI 34·3–41·7) with 72·5% (95% CI 66·9–78·0) seeking medical care. The average H1N1 positive rate in individuals reporting ILI and testing by polymerase chain reaction was 22·7%. A total of 611 000–768 000 people, or 4·7–5·9% of the Shenzhen population, are estimated to have experienced H1N1 influenza. The estimated total number of cases of H1N1 is likely to be 330 times greater than the number of laboratory-confirmed cases.
Selective serotonin reuptake inhibitor use is associated with increased risk of suicidal ideation in adolescent humans, yet the neuropharmacological basis of this phenomenon is unknown. Consequently, we examined the behavioural and neurochemical effects of chronic paroxetine (PRX) treatment in adult and adolescent rats. Rats received PRX in their drinking water (target dose 10 mg/kg) for 22 d, during which time they were assessed for depression- and anxiety-like behaviours. Subsequent ex-vivo analyses examined serum PRX concentrations, striatal neurotransmitter content, and regional serotonin and dopamine transporter (SERT, DAT) binding density. After 11–12 d treatment, PRX-treated adolescent rats showed a significant inhibition of social interaction while adults were unaffected. After 19–20 d treatment, adolescents failed to show an antidepressant-like effect of PRX treatment on the forced swim test (FST), while PRX-treated adults showed a typical decrease in immobility and increase in swimming. Two PRX-treated adolescents died unexpectedly after the FST suggesting a compromised response to physical stress. Despite their greater apparent adverse reaction to the drug, adolescents had significantly lower plasma PRX than adults at day 22 of treatment. Chronic PRX treatment had similar effects in adults and adolescents on striatal 5-HT (unchanged relative to controls) and 5-HIAA levels (decreased), while markers of dopaminergic function (DOPAC, HVA, DA turnover) were increased in adults only. SERT density was up-regulated in the amygdala in PRX-treated adolescents only while DAT density in the nucleus accumbens was down-regulated only in PRX-treated adults. These data suggest that the immature rat brain responds differently to PRX and that this might be of use in modelling the atypical response of human adolescents to antidepressants. The age-specific PRX-induced changes in dopaminergic markers and SERT and DAT binding provide clues as to the neural mechanisms underlying adverse PRX effects in adolescent humans.
High resolution far infrared absorption measurements were carried out for single walled and double walled carbon nanotubes samples (SWCNT and DWCNT) encased in a polyethylene matrix to investigate the temperature and bundling effects on the low frequency phonons associated with the low frequency circumferential vibrations. At a temperature where kBT is significantly lower than the phonon energy, the broad absorption features as observed at room temperature become well resolved phonon transitions. For a DWCNT sample whose inner tubes have a similar diameter distribution as the SWCNT sample studied, a series of sharp features were observed at room temperature at similar positions as for the SWCNT samples studied. The narrow linewidth is attributed to the fact that the inner tubes are isolated from the polyethylene matrix and the weak inter-tubule interactions. More systematic studies will be required to better understand the effects of inhomogeneous broadening and thermal-excitation on the detailed position and lineshape of the low frequency phonon features in carbon nanotubes.
An overview on current trends in stimulated Brillouin scattering and optical phase conjugation is given. This report is based on the results of the “Second International Workshop on stimulated Brillouin scattering and phase conjugation” held in Potsdam/Germany in September 2007. The properties of stimulated Brillouin scattering are presented for the compensation of phase distortions in combination with novel laser technology like ceramics materials but also for e.g., phase stabilization, beam combination, and slow light. Photorefractive nonlinear mirrors and resonant refractive index gratings are addressed as phase conjugating mirrors in addition.
Particulate organic matter (POM), dissolved organic matter (DOM), bacteria and cladoceran were sampled seasonally at
Zhihugang Estuary and Lake Center in Taihu Lake. The δ13C of the four organic matter fractions showed consistent temporal
variation, with heaviest values in summer and lower at other times of the year. The cladoceran δ13C showed a significant
correlation with that of POM, reflecting a heavy dietary dependence on POM during the study period. The bacteria became
enriched in 13C compared with that of DOM throughout the sampling dates, although no significant relationship was found
between the two fractions. δ13C values of POM, cladoceran and bacteria were all negative significantly correlated with oxidation
and reduction potential (ORP), and specific conductivity (SpCond). As for δ15N, the seasonal pattern of food web components
was variable. The POM δ15N signature exhibited the most enriched isotope ratios during the summer months when dissolved
inorganic nitrogen (DIN) nutrients were at their lowest concentrations. The consumption of DIN in summer can explain in part
the progressive accumulation of heavy nitrogen isotopes during this period. Spatially, δ13C and δ15N of the food web components
were all slightly depleted at Estuary than that at Lake Center during the study period, possibly due to large allochthonous inputs
at Zhihugang Estuary. Relatively wide ranges of stable isotopic values from both sites suggest that seasonality should be
considered when attempting to establish food web structures in a eutrophic lake.
Bifurcation phenomenon in the energy-angular correlation spectrum of the vacuum laser acceleration has been observed with computer simulation. Concerning a focused laser pulse, the classical single-valued energy-angular correlation spectrum for a plane wave is, besides broadened to a band, bifurcated with the classical value in between the two branches. Analytic expression to describe the correlation has been derived and physical explanations based on the ponderomotive potential model and Lorentz-Newton force analyses are presented. The theoretical results are supported by numerical simulations which have been compared with the experimental results. This study is helpful in designing vacuum laser acceleration experiments.
Concerning laser-driven electron acceleration in vacuum, a comparison was made between using circularly polarized (CP) laser field and linearly polarized (LP) field. It has been found that the main advantage for using CP field is that its acceleration channel occupies relatively larger phase space, which can give rise to greater acceleration efficiency. This feature chiefly comes from the difference in the distribution of the longitudinal electric components of these two kinds of fields. One of the disadvantages with CP field is the “energy saturation” phenomenon as the laser intensity is sufficiently high, resulting from the enhanced Lorentz force component in CP field. Physical explanations of these characteristics are addressed as well.