To investigate the risk factors associated with the development of thrombocytopenia, and define the thresholds of efficacy and safety in critically ill patients who received linezolid therapy. A ...retrospective study was performed in critically ill patients treated with linezolid. Risk factors associated with thrombocytopenia were identified via medical records and trough levels (C
min
) measured during linezolid treatment. By establishing a logistic model, the risks were predicted by the receiver operating characteristic (ROC) curve and the thresholds of efficacy and safety were identified in the patients. Logistic analysis showed that, weight (OR = 0.906; 95 % CI, 0.839–0.978;
P
= 0.011), baseline platelet count (OR = 0.989; 95 % CI, 0.977–1.000;
P
= 0.049), C
min
(OR = 1.545; 95 % CI, 1.203–1.983;
P
= 0.001), and APACHE II score (OR = 1.130; 95 % CI, 1.003–1.273;
P
= 0.044) were significant factors for linezolid-associated thrombocytopenia. The area under the ROC curve of the combined predictor was larger based on the above factors. When the Youden index was the maximum, the best optimal cut-off point was 205.6 on the ROC curve; when C
min
≥ 2 mg/L, the probability of bacterial eradication was more than 80 %; when C
min
≥ 6.3 mg/L, the probability of thrombocytopenia was more than 50 %. In clinical practice, when the calculating results of the combined predictor ≤205.6, the risk of the development of thrombocytopenia may be higher. Furthermore, maintenance of C
min
between 2 and 6.3 mg/L over time may be helpful in retaining appropriate efficacy and reducing the associated thrombocytopenia.
As a carrier of deformation information, the speckle pattern, or more exactly the random intensity distributions, which could be naturally occurred or artificially fabricated onto test samples’ ...surface, plays an indispensable role in digital image correlation (DIC). It is now well recognized that the accuracy and precision in DIC measurements not only rely on correlation algorithms, but also depend highly on the quality of the speckle pattern. Considering the huge diversity in test materials, spatial scales and experimental conditions, speckle pattern fabrication could be a challenging issue facing DIC practitioners. To obtain good speckle patterns suitable for DIC measurements, some key issues of fabrication methods and quality assessment of speckle patterns must be well addressed. To this end, this review systematically presents the speckle pattern classification and fabrication techniques for various samples and scales, as well as some typical quality assessment metrics.
On‐treatment levels of hepatitis B surface antigen (HBsAg) may predict response to peginterferon (PEG‐IFN) therapy in chronic hepatitis B (CHB), but previously proposed prediction rules have shown ...limited external validity. We analyzed 803 HBeAg‐positive patients treated with PEG‐IFN in three global studies with available HBsAg measurements. A stopping‐rule based on absence of a decline from baseline was compared to a prediction‐rule that uses HBsAg levels of <1,500 IU/mL and >20,000 IU/mL to identify patients with high and low probabilities of response. Patients with an HBsAg level <1,500 IU/mL at week 12 achieved response (HBeAg loss with HBV DNA <2,000 IU/mL at 6 months posttreatment) in 45%. At week 12, patients without a decline in HBsAg achieved a response in 14%, compared to only 6% of patients with HBsAg >20,000 IU/mL, but performance varied across HBV genotype. In patients treated with PEG‐IFN monotherapy (n = 465), response rates were low in patients with genotypes A or D if there was no decline of HBsAg by week 12 (negative predictive value NPV: 97%‐100%), and in patients with genotypes B or C if HBsAg at week 12 was >20,000 IU/mL (NPV: 92%‐98%). At week 24, nearly all patients with HBsAg >20,000 IU/mL failed to achieve a response, irrespective of HBV genotype (NPV for response and HBsAg loss 99% and 100%). Conclusion: HBsAg is a strong predictor of response to PEG‐IFN in HBeAg‐positive CHB. HBV genotype‐specific stopping‐rules may be considered at week 12, but treatment discontinuation is indicated in all patients with HBsAg >20,000 IU/mL at week 24, irrespective of HBV genotype. (Hepatology 2013;53:872–880)
Emerging evidences suggest that necrosis is programmed and is one of the main forms of cell death in the pathological process in cardiac diseases. Long noncoding RNAs (lncRNAs) are emerging as new ...players in gene regulation. However, it is not yet clear whether lncRNAs can regulate necrosis in cardiomyocytes. Here, we report that a long noncoding RNA, named necrosis-related factor (NRF), regulates cardiomyocytes necrosis by targeting miR-873 and RIPK1 (receptor-interacting serine/threonine-protein kinase 1)/RIPK3 (receptor-interacting serine/threonine-protein kinase 3). Our results show that RIPK1 and RIPK3 participate in H2O2-induced cardiomyocytes necrosis. miR-873 suppresses the translation of RIPK1/RIPK3 and inhibits RIPK1/RIPK3-mediated necrotic cell death in cardiomyocytes. miR-873 reduces myocardial infarct size upon ischemia/reperfusion (I/R) injury in the animal model. In exploring the molecular mechanism by which miR-873 expression is regulated, we identify NRF as an endogenous sponge RNA and repress miR-873 expression. NRF directly binds to miR-873 and regulates RIPK1/RIPK3 expression and necrosis. Knockdown of NRF antagonizes necrosis in cardiomyocytes and reduces necrosis and myocardial infarction upon I/R injury. Further, we identify that p53 transcriptionally activates NRF expression. P53 regulates cardiomyocytes necrosis and myocardial I/R injury through NRF and miR-873.Our results identify a novel mechanism involving NRF and miR-873 in regulating programmed necrosis in the heart and suggest a potential therapeutic avenue for cardiovascular diseases.
ABSTRACT We present preliminary results of the quasar survey in the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) first data release (DR1), which includes the pilot survey and ...the first year of the regular survey. There are 3921 quasars reliably identified, among which 1180 are new quasars discovered in the survey. These quasars are at low to median redshifts, with a highest z of 4.83. We compile emission line measurements around the H , Hβ, Mg ii, and C iv regions for the new quasars. The continuum luminosities are inferred from SDSS photometric data with model fitting, as the spectra in DR1 are non-flux-calibrated. We also compile the virial black hole mass estimates, with flags indicating the selection methods, and broad absorption line quasars. The catalog and spectra for these quasars are also available. Of the 3921 quasars, 28% are independently selected with optical-infrared colors, indicating that the method is quite promising for the completeness of the quasar survey. LAMOST DR1 and the ongoing quasar survey will provide valuable data for studies of quasars.
Summary
Background
Tinea capitis is still common in developing countries, such as China. Its pathogen spectrum varies across regions and changes over time.
Objectives
This study aimed to clarify the ...current epidemiological characteristics and pathogen spectrum of tinea capitis in China.
Methods
A multicentre, prospective descriptive study involving 29 tertiary hospitals in China was conducted. From August 2019 to July 2020, 611 patients with tinea capitis were enrolled. Data concerning demography, risk factors and fungal tests were collected. When necessary, the pathogens were further identified by morphology or molecular sequencing in the central laboratory.
Results
Among all enrolled patients, 74·1% of the cases were in patients aged 2–8 years. The children with tinea capitis were mainly boys (56·2%) and were more likely than adults to have a history of animal contact (57·4% vs. 35·3%, P = 0·012) and zoophilic dermatophyte infection (73·5% vs. 47%). The adults were mainly female (83%) and were more likely than children to have anthropophilic agent infection (53% vs. 23·9%). The most common pathogen was zoophilic Microsporum canis (354, 65·2%), followed by anthropophilic Trichophyton violaceum (74, 13·6%). In contrast to the eastern, western and northeastern regions, where zoophilic M. canis predominated, anthropophilic T. violaceum predominated in central China (69%, P < 0·001), where the patients had the most tinea at other sites (20%) and dermatophytosis contact (26%) but the least animal contact (39%). Microsporum ferrugineum was the most common anthropophilic agent in the western area, especially in Xinjiang province.
Conclusions
Boys aged approximately 5 years were the most commonly affected group. Dermatologists are advised to pay more attention to the different transmission routes and pathogen spectra in different age groups from different regions.
What is already known about this topic?
Tinea capitis is an infection of the scalp and hair caused by dermatophytes and is still common in developing countries. Prepubertal children are mainly affected.
The pathogen spectrum of tinea capitis varies across different geographical areas and changes over time.
Nationwide prospective epidemiological surveys of tinea capitis in China are rare and out of date.
What does this study add?
This study provides data concerning the epidemiological characteristics and pathogen spectrum of tinea capitis in contemporary China.
Boys aged approximately 5 years were most commonly affected and were more likely than adults to have zoophilic dermatophyte infection.
The main pathogens of tinea capitis in China are zoophilic dermatophytes, mainly Microsporum canis. In contrast to the other regions, the predominant pathogens in central China are anthropophilic dermatophytes.
Plain language summary available online
Voriconazole is frequently utilized for the prevention and treatment of invasive fungal infections (IFIs), and is extensively metabolized by the cytochrome P450 (CYP) system. The impact of activity ...of the genes encoding CYP3A4, CYP3A5, and CYP2C9 on the pharmacokinetics of voriconazole cannot be ignored because, second to CYP2C19, they are the most important enzymes involved in voriconazole metabolism. The influence of genetic polymorphisms in
CYP3A4
,
CYP3A5
, and
CYP2C9
on the plasma concentrations of voriconazole was evaluated in the present study. The study cohort comprised 158 patients with IFIs in whom 22 single-nucleotide polymorphisms (SNPs) in
CYP3A4
,
CYP3A5
, and
CYP2C9
were genotyped using the Sequenom MassARRAY RS1000 system, and voriconazole plasma concentrations were measured by high-performance liquid chromatography (HPLC). 40, 91, and 27 patients presented with low (<1 mg/L), normal (1–4 mg/L), and high (>4 mg/L) plasma voriconazole concentrations, respectively. Correlation analysis between polymorphisms and the plasma voriconazole concentration revealed an association between the presence of the rs4646437 T allele and a higher plasma voriconazole concentration
p
= 0.033, odds ratio (OR) = 2.832, 95 % confidence interval (CI) = 1.086–7.384. This study has identified a new SNP related to the metabolism of voriconazole, potentially providing novel insight into the influence of CYP3A4 on the pharmacokinetics of this antifungal agent.
Summary
The aims of our meta‐analysis were (i) to quantify the predictability of childhood overweight and obesity on the risk of incident asthma; and (ii) to evaluate the gender difference on this ...relationship. The selection criteria included prospective cohort paediatric studies which use age‐ and sex‐specific body mass index (BMI) as a measure of childhood overweight and the primary outcome of incident asthma. A total of 1,027 studies were initially identified through online database searches, and finally 6 studies met the inclusion criteria. The combined result of reported relative risk from the 6 included studies revealed that overweight children conferred increased risks of incident asthma as compared with non‐overweight children (relative risk, 1.19; 95% confidence interval CI, 1.03–1.37). The relationship was further elevated for obesity vs. non‐obesity (relative risk, 2.02; 95% CI, 1.16–3.50). A dose–responsiveness of elevated BMI on asthma incidence was observed (P for trend, 0.004). Obese boys had a significantly larger effect than obese girls (relative risk, boys: 2.47; 95% CI, 1.57–3.87; girls: 1.25; 95% CI, 0.51–3.03), with significant dose‐dependent effect. Proposed mechanisms of gender difference could be through pulmonary mechanics, sleep disordered breathing and leptin. Further research might be needed to better understand the exact mechanism of gender difference on the obesity–asthma relationship.
Parasitic wasps rely on olfaction to locate their hosts in complex chemical environments. Odorant receptors (ORs) function together with well‐conserved odorant coreceptors (ORcos) to determine the ...sensitivity and specificity of olfactory reception. Campoletis chlorideae (Hymenoptera: Ichneunmonidae) is a solitary larval endoparasitoid of the cotton bollworm, Helicoverpa armigera, and some other noctuid species. To understand the molecular basis of C. chlorideae’s olfactory reception, we sequenced the transcriptome of adult male and female heads (including antennae) and identified 211 OR transcripts, with 95 being putatively full length. The tissue expression profiles, as assessed by reverse‐transcription PCR, showed that seven ORs were expressed only or more highly in female antennae. Their functions were analysed using the Xenopu slaevis oocyte expression system and two‐electrode voltage‐clamp recordings. CchlOR62 was tuned to cis‐jasmone, which was attractive to female C. chlorideae adults and H. armigera larvae in the subsequent behavioural assays. Further bioassays using caged plants showed that the parasitism rate of H. armigera larvae by C. chlorideae on cis‐jasmone‐treated tobacco plants was higher than on the control plants. Thus, cis‐jasmone appears to be an important infochemical involved in the interactions of plants, H. armigera and C. chlorideae, and CchlOR62 mediates the attractiveness of cis‐jasmone to C. chlorideae.