[A multicenter epidemiological study of acute bacterial meningitis in children].

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum ß-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ2=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.

Phenotypic and genetic correlations of pork myoglobin content with meat colour and other traits in an eight breed-crossed heterogeneous population.

Meat colour is one of the most important meat quality traits affecting consumption desire. Genetic improvement for meat colour traits is not so easy because pigs can be phenotyped only after slaughter. Besides the parameters from the optical instrument, other indexes that reflect the material basis of meat colour should be measured accurately and used in the genomic analysis. Myoglobin (Mb) is the main chemical component determining meat colour. However, to what extent the Mb content contributes to meat colour, and whether it can be used as a trait for pig breeding to improve meat colour, and the correlations of Mb content with complex porcine traits are largely unknown. To address these questions, we measured the muscle Mb content in 624 pigs from the 7th generation of a specially designed eight breed-crossed pig heterogeneous population, evaluated its phenotypic and genetic correlations with longissimus thoracis colour score at 24 h after slaughter. More than that, we also systematically phenotyped more than 100 traits on these animals to evaluate the potential correlations between muscle Mb content and economically important traits. Our results showed that the average muscle Mb content in the 624 pigs was 1.00 mg/g, ranging from 0.51 to 2.17 mg/g. We found that higher Mb content usually correlated with favourable meat colour, higher marbling score, less moisture content, and less drip loss. Genetic correlation analysis between muscle Mb content and 101 traits measured in this study shows that Mb content is also significantly correlated with 31 traits, including marbling, shear force, firmness, and juiciness. To our knowledge, this is one of the largest studies about the correlations of muscle Mb content with as many as 100 various traits in a large-scale genetically diversified population. Our results showed that the Mb content could be a selection parameter for the genetic improvement of meat colour. The selection for higher Mb content will also benefit marbling, shear force, firmness, and overall liking but might not affect the growth, carcass, and fat deposition traits.

[Effect of androgen replacement therapy on mixed dry eye in a rabbit model].

Objective: To explore the effect of androgen replacement therapy in a rabbit dry eye model characterized by androgen deficiency and meibomian gland dysfunction (MGD). Methods: Thirty 6-month-old male Chinchilla rabbits were randomly divided into the treatment group, model group and control group, with 10 rabbits in each group. In the treatment and model groups, 2/3 of the meibomian gland openings were closed by cauterization with electric coagulation pen, and bilateral testes were removed. One gram gel containing 1% testosterone was applied for 28 days on the skin of rabbits in the treatment group since day 28 after the surgery. The model group and control group received transdermal petrolatum instead. Tear secretion, tear breakup time (TBUT), corneal fluorescein staining, and serum free testosterone level were monitored throughout the study period. The globes and eyelids were collected for hematoxylin-eosin staining and periodic acid-Schiff staining. Conjunctival tissue was tested for the expression of miRNA-744-5p and interleukin-6. Meibum was collected for fatty acid analysis. Results: Animals presented with typical dry eye signs and androgen deficiency. After 28-day androgen replacement therapy, compared with the model group, the treatment group had a significantly higher tear secretion rate [(14.7±5.2) vs (10.3±3.6) mm, P=0.001], higher TBUT [(15.0±4.2) vs (10.2±3.6) s, P=0.003], lower fluorescein staining score [0 (0, 1) vs 2 (1, 4), P<0.001], and higher goblet cell density at conjunctival fornix (27.2±7.6 vs 10.7±4.8, P<0.001). Additionally, compared with the model group, the conjunctiva of the treatment group expressed a significantly lower level of miRNA-744-5p (1.67±0.24 vs 2.63±0.58, P<0.001) and interleukin-6 [2.38 (1.84, 4.61) vs 4.82 (3.99, 6.36), P=0.022]. Meanwhile, the treatment group showed significantly increased level of 16∶1, Δ9 fatty acid [(10.31±1.00)% vs (3.87±0.45)%, P<0.001] and iso-18∶0 fatty acid [(7.09±0.93)% vs (2.44±0.70)%, P<0.001], but decreased level of iso-26∶0 fatty acid [(5.72±1.07)% vs (8.02±0.65)%, P<0.001] in the meibum compared with the model group. Conclusion: Androgen replacement therapy can alleviate dry eye signs in rabbits presented with combined androgen deficiency and MGD.

Thermodynamic method for establishment of relationship between icephobicity/superhydrophobicity and microstructure-Based on computing for adhesion work.

Superhydrophobic surfaces (SHS) have potential in solving the icing of aircraft, high-voltage overhead transmission lines, and other power network devices exposed to the air. For this reason, we wish to establish the relationship between microstructure and the adhesion work by thermodynamic method, also for analysis of the relationship between the hydrophobicity and icephobicity (or anti-icing). Therefore, respectively considering Cassie-Baxter and Wenzel states, such relationship was theoretically established based on one/two-step surface model, enlightened by natural and artificial SHS. Among it, how to obtain the adhesion work of icing per unit ice-solid interface is the key to this study. Followed by it, hydrothermal experiment, chemical deposition, and etching methods were performed to verify our theoretical results. •How to model for the SHS based on the natural and artificial SHS;•Computation for adhesion work (waw) per unit area of a water droplet-SHS interface;•Computation for adhesion work (wai) per unit area of a frozen water droplet-SHS interface;•Computation for reduced adhesion work (wa2) after icing;•Hydrothermal experiment, chemical deposition and etching methods were used for validation of modeling.

Mechanical stress contributes to osteoarthritis development through the activation of transforming growth factor beta 1 (TGF-ß1).

OBJECTIVES: The role of mechanical stress and transforming growth factor beta 1 (TGF-ß1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known. METHODS: In this study, TGF-ß1 from osteoclasts and knee joints were analyzed using a co-cultured cell model and an OA rat model, respectively. Five patients with a femoral neck fracture (four female and one male, mean 73.4 years (68 to 79)) were recruited between January 2015 and December 2015. Results showed that TGF-ß1 was significantly upregulated in osteoclasts by cyclic loading in a time- and dose-dependent mode. The osteoclasts were subjected to cyclic loading before being co-cultured with chondrocytes for 24 hours. RESULTS: A significant decrease in the survival rate of co-cultured chondrocytes was found. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay demonstrated that mechanical stress-induced apoptosis occurred significantly in co-cultured chondrocytes but administration of the TGF-ß1 receptor inhibitor, SB-505124, can significantly reverse these effects. Abdominal administration of SB-505124 can attenuate markedly articular cartilage degradation in OA rats. CONCLUSION: Mechanical stress-induced overexpression of TGF-ß1 from osteoclasts is responsible for chondrocyte apoptosis and cartilage degeneration in OA. Administration of a TGF-ß1 inhibitor can inhibit articular cartilage degradation.Cite this article: R-K. Zhang, G-W. Li, C. Zeng, C-X. Lin, L-S. Huang, G-X. Huang, C. Zhao, S-Y. Feng, H. Fang. Mechanical stress contributes to osteoarthritis development through the activation of transforming growth factor beta 1 (TGF-ß1). Bone Joint Res 2018;7:587-594. DOI: 10.1302/2046-3758.711.BJR-2018-0057.R1.

Optical properties of surface states in two-dimensional topological insulators.

We present a simple and tractable approach to investigate the optical properties of surface states in two-dimensional (2D) topological insulators (TIs). The analytic expression of optical conductivity of surface states in 2D TIs are obtained based on the kinetic equations. It is found that universal optical conductance can be observed in the high frequency region, which does not depend on the temperature, the chemical potential, or the bandgap of the systems. This universal optical conductance is similar to that in graphene. However, the optical absorption edge of such surface states strongly depend on the chemical potential and the bandgap of the systems. There are obvious optical absorption peaks at low temperature in the low frequency region, which are very different from that in graphene. The bandgaps in surface states can be accurately experimentally measured by the optical absorption edges or the peaks. We expect that our theoretical results offer transparent understandings for the experimental results and applications of 2D TIs.

Fetal vitamin D concentration and growth, adiposity and neurodevelopment during infancy.

BACKGROUND/OBJECTIVES: To determine the association between cord blood 25-hydroxyvitamin D (25(OH)D) concentration with growth, adiposity and neurodevelopment during infancy. SUBJECTS/METHODS: Serum 25(OH)D was measured in cord blood by the liquid chromatography tandem mass spectrometry (LC-MS/MS) from the Shanghai's "Allergy and Obesity Cohort study" (n = 1244). Weight, length, head circumference, and body mass index (BMI) z-scores for age were calculated based on World Health Organization Standard (at 6 months, 1 years, and 2 years). Neurodevelopment was measured at 2 years using Ages and Stages Questionnaire. Generalized estimating equation and multivariable logistic regression model were exploited to examine associations between fetal 25(OH)D concentration and offspring outcomes. RESULTS: The median of the 25(OH)D concentration in cord blood was 22.4 ng/ml (interquartile range, 27.3-8.6). Infants born in winter had lower 25(OH)D concentration. 25(OH)D deficiency was not associated with weight z-score (mean difference, 0.07; 95% confidence internal (CI), -0.09 to 0.23), length z-score (mean difference, 0.01; 95% CI, -0.19 to 0.21), head circumference z-score (mean difference, -0.06; 95% CI, -0.27 to 0.15) and BMI z-score (mean difference, 0.09; 95% CI, -0.07 to 0.25) or neurodevelopment during infancy, adjusting for sex, socio-economic position, pre-pregnancy maternal BMI, and maternal and neonatal characteristics. The associations did not vary by gender. A sensitivity analysis of available case analysis showed virtually the same results. CONCLUSIONS: Fetal vitamin D concentration was not associated with growth, adiposity or neurodevelopment during infancy. The role of vitamin D concentration and its mechanistic pathway in the early origins of adiposity needs to be clarified.

A whole genome sequence association study for puberty in a large Duroc × Erhualian F2 population.

A large proportion of gilts and sows are culled from reproduction populations because of anestrus and pubertal reproductive failure. Selecting early onset of puberty gilts has a favorable effect on sows' reproductivity. However, age at puberty is hard to be routinely measured in commercial herds. With molecular genetic predictors, identifying individuals that have a propensity for early onset of puberty can be simplified. We previously performed genome scanning and a genome-wide association study for puberty in an F2 resource population using 183 microsatellites and 62 125 SNPs respectively. The detection power and resolution of identified quantitative trait loci were very low. Herein, we re-sequenced 19 founders of the F2 resource population in high coverage, and whole genome sequences of F2 individuals were imputed to perform an association study for reproductive traits. A total of 2339 SNPs associated with pubertal reproductive failure were identified in the region of 30.94-40.74 Mb on SSC7, with the top one, positioned at 33.36 Mb, explaining 16% of the phenotypic variances. We improved the magnitude of the P-value by 10E+5 to 10E+7 using the whole genome sequence rather than using low/middle density markers as in previous studies, and we narrowed down the QTL confidence interval to 5.25 Mb. Combining the annotation of gene function, RAB23 and BAK1 were perceived as the most compelling candidate genes. The identified loci may be useful in culling sows failing to show estrus by marker-assisted selection to increase reproductive efficiency of swine herds.

GENOME-WIDE MAPPING OF COPY NUMBER VARIATIONS IN COMMERCIAL HYBRID PIGS USING A HIGH-DENSITY SNP GENOTYPING ARRAY.

Copy number variations (CNVs) are important forms of structural variation in human and animals and can be considered as a major genetic component of phenotypic diversity. Here we used the Illumina PorcineSNP60 BeadChip V2 and a DLY [Duroc x (Large White x Landrace)] commercial hybrid population to identify 272 CNVs belonging to 165 CNV regions (CNVRs), of which 66 are new. As CNVRs are specific to origin of population, our DLY-specific data is an important complementary to the existing CNV map in the pig genome. Eight CNVRs were selected. for validation by quantitative real-time PCR (qRT-PCR) and the accurate rate was high (87.25%). Gene function analysis suggested that a common CNVR may play an important role in multiple traits, including growth rate and carcass quality.

A genome-wide association analysis for susceptibility of pigs to enterotoxigenic Escherichia coli F41.

Enterotoxigenic Escherichia coli (ETEC) is a type of pathogenic bacteria that cause diarrhea in piglets through colonizing pig small intestine epithelial cells by their surface fimbriae. Different fimbriae type of ETEC including F4, F18, K99 and F41 have been isolated from diarrheal pigs. In this study, we performed a genome-wide association study to map the loci associated with the susceptibility of pigs to ETEC F41 using 39454 single nucleotide polymorphisms (SNPs) in 667 F2 pigs from a White Duroc×Erhualian F2 cross. The most significant SNP (ALGA0022658, P=5.59×10-13) located at 6.95 Mb on chromosome 4. ALGA0022658 was in high linkage disequilibrium (r 2>0.5) with surrounding SNPs that span a 1.21 Mb interval. Within this 1.21 Mb region, we investigated ZFAT as a positional candidate gene. We re-sequenced cDNA of ZFAT in four pigs with different susceptibility phenotypes, and identified seven coding variants. We genotyped these seven variants in 287 unrelated pigs from 15 diverse breeds that were measured with ETEC F41 susceptibility phenotype. Five variants showed nominal significant association (P<0.05) with ETEC F41 susceptibility phenotype in International commercial pigs. This study provided refined region associated with susceptibility of pigs to ETEC F41 than that reported previously. Further works are needed to uncover the underlying causal mutation(s).

Genome-wide association study identifies QTLs for EBV of backfat thickness and average daily gain in Duroc pigs.

Backfat thickness (BFT) and average daily gain (ADG) are two important economic traits in commercial swine production. Identifying QTLs and uncovering the molecular mechanism for BFT and ADG would greatly help to speed up the breeding progress. In current breeding program, EBV for these two traits are calculated and formulated a comprehensive breeding index, which then be used to improve pig performance. Using Illumina PorcineSNP60 BeadChip, a pilot genomewide association studies (GWAS) for BFT and ADG in 83 Duroc pigs were performed. A total of 31 genome-wise significant SN Ps were detected to be associated with BFT on SSC 4, 9, 11, 12 and 14, ten of which were coincident with previously reported QTL regions. There are two genome-wise loci prominently associated with ADG on SSC2 and SSC13, respectively. The two loci on SSC2 are well overlapped with the QTL regions previously reported. All the 31 significant SNPs associated with BFT are verified on 219 outbreed pigs, six SN Ps reach an extreme significant level and seven SNP reaches a significant level, CACNA1E and ACBD6 are chosen as positional candidate genes. Our findings not only confirmed previously findings, but also revealed a number of novel SNPs associated with BFT and ADG. Two positional candidate genes CACNA1E and ACBD6 were identified for further study. These results would facilitate the identification of causative genes for BFT and ADG.

A genomewide association study of feed efficiency and feeding behaviors at two fattening stages in a White Duroc × Erhualian F population.

Feeding efficiency is a multifactorial and economically important trait in pigs. Genetic improvement of feeding efficiency will greatly benefit the pig industry. In the past decades, the hog market weight has increased worldwide. However, whether the genetic architecture of feeding efficiency is same or not at early and late fattening periods is unclear. To map genomic regions for feed efficiency and feeding behavior traits at early (n ≥ 384) and late (n ≥ 334) growth stages in pigs, we performed genomewide association studies for feed to gain ratio (FCR), residual feed intake (RFI), daily feed intake, daily visit times, daily feeding time (DFT), feed intake per second (FIPS), and feed intake per visit during 3 periods (2 stages and overall) in a White Duroc × Erhualian F2 intercross population. Six chromosomal regions showed significant association with these traits, of which 4 loci were reported for the first time. Our results confirmed the QTL of FCR around 34 Mb on SSC7 and RFI around 134 Mb on SSC12. Of note, 2 regions were associated with more than 1 trait. One was around 36 Mb on SSC7, and there were 47 and 67 SNP associated with FCR from 120 to 210 and from 120 to 240 d, respectively. The top SNP is located in a 2.88-Mb linkage disequilibrium (LD) block that harbors 44 genes. We propose the high mobility group AT-hook 1 gene as a plausible candidate gene in this region. The other was evidenced around 53 Mb on SSC12, which had multiple association signals for DFT and FIPS. The top SNP is located in a 211-kb LD block that harbors only 1 annotated gene, WSCD1, which encodes a protein with sulfotransferase activity and involves the glucose metabolism and, therefore, appears to be a plausible candidate gene. Except the region on SSC12 associated with DFT at both stages, the rest of the regions associated with the traits at only 1 stage, so the genetic architectures of the 2 stages are not same.

SUSCEPTIBILITY LOCI FOR UMBILICAL HERNIA IN SWINE DETECTED BY GENOME-WIDE ASSOCIATION.

Umbilical hernia (UH) is a complex disorder caused by both genetic and environmental factors. UH brings animal welfare problems and severe economic loss to the pig industry. Until now, the genetic basis of UH is poorly understood. The high-density 60K porcine SNP array enables the rapid application of genome-wide association study (GWAS) to identify genetic loci for phenotypic traits at genome wide scale in pigs. The objective of this research was to identify susceptibility loci for swine umbilical hernia using the GWAS approach. We genotyped 478 piglets from 142 families representing three Western commercial breeds with the Illumina PorcineSNP60 BeadChip. Then significant SNPs were detected by GWAS using ROADTRIPS (Robust Association-Detection Test for Related Individuals with Population Substructure) software base on a Bonferroni corrected threshold (P = 1.67E-06) or suggestive threshold (P = 3.34E-05) and false discovery rate (FDR = 0.05). After quality control, 29,924 qualified SNPs and 472 piglets were used for GWAS. Two suggestive loci predisposing to pig UH were identified at 44.25MB on SSC2 (rs81358018, P = 3.34E-06, FDR = 0.049933) and at 45.90MB on SSC17 (rs81479278, P = 3.30E-06, FDR = 0.049933) in Duroc population, respectively. And no SNP was detected to be associated with pig UH at significant level in neither Landrace nor Large White population. Furthermore, we carried out a meta-analysis in the combined pure-breed population containing all the 472 piglets. rs81479278 (P = 1.16E-06, FDR = 0.022475) was identified to associate with pig UH at genome-wide significant level. SRC was characterized as plausible candidate gene for susceptibility to pig UH according to its genomic position and biological functions. To our knowledge, this study gives the first description of GWAS identifying susceptibility loci for umbilical hernia in pigs. Our findings provide deeper insights to the genetic architecture of umbilical hernia in pigs.

A joint genomewide association analysis of pig leg weakness and its related traits in an F2 population and a Sutai population.

To map genomic loci for leg weakness-related traits in pigs, leg scores and gait scores were recorded at 219 ± 18 d in a White Duroc × Erhualian F2 intercross population and a Chinese Sutai population. The biceps brachii muscle was dissected from the right front leg and its length and weight were measured after slaughter at 240 ± 3 d in the 2 populations. The 2 populations were genotyped using the Porcine SNP60 BeadChip, and genomewide association studies were performed on them separately and jointly. A total of 12 significant loci were detected in the 3 populations, including 6 at the 1% genomewide significant level on SSC7 and SSCX and 2 at the 5% genomewide significant level on SSC7 and SSCX. All of them confirmed the previous QTL findings except 1 locus for gait score of front legs on SSC5, which was reported for the first time. The most prominent locus was identified in a 2.15 Mb linkage disequilibrium block on SSC7 for both leg weakness and the growth of the biceps brachii muscle, which is worth further investigation. The significant SNP identified in the Sutai population could directly be explored in marker-assisted selection to improve leg soundness of the Sutai pig. As expected, it is generally more powerful to identify significant regions in the combined population compared with a single population. To our knowledge, this was the first genomewide association study for weight and length of the biceps brachii muscle in pigs.

Worldwide genetic relationships of pigs as inferred from X chromosome SNPs.

The phylogeography of the porcine X chromosome has not been studied despite the unique characteristics of this chromosome. Here, we genotyped 59 single nucleotide polymorphisms (SNPs) in 312 pigs from around the world, representing 39 domestic breeds and wild boars in 30 countries. Overall, widespread commercial breeds showed the highest heterozygosity values, followed by African and American populations. Structuring, as inferred from FST and analysis of molecular variance, was consistently larger in the non-pseudoautosomal (NPAR) than in the pseudoautosomal regions (PAR). Our results show that genetic relationships between populations can vary widely between the NPAR and the PAR, underscoring the fact that their genetic trajectories can be quite different. NPAR showed an increased commercial-like genetic component relative to the PAR, probably because human selection processes to obtain individuals with high productive parameters were mediated by introgressing boars rather than sows.