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Assessment of liver reserve function (LRF) is essential for predicting the prognosis of patients with chronic liver disease (CLD) and determines the extent of liver resection in patients with hepatocellular carcinoma.To establish noninvasive models for LRF assessment based on liver stiffness measurement (LSM) and to evaluate their clinical performance.A total of 360 patients with compensated CLD were retrospectively analyzed as the training cohort. The new predictive models were established through logistic regression analysis and were validated internally in a prospective cohort (132 patients).Our study defined indocyanine green retention rate at 15 min (ICGR15) ≥ 10% as mildly impaired LRF and ICGR15 ≥ 20% as severely impaired LRF. We constructed predictive models of LRF, named the mLPaM and sLPaM, which involved only LSM, prothrombin time international normalized ratio to albumin ratio (PTAR), age and model for end-stage liver disease (MELD). The area under the curve of the mLPaM model (0.855, 0.872, respectively) and sLPaM model (0.869, 0.876, respectively) were higher than that of the methods for MELD, albumin-bilirubin grade and PTAR in the two cohorts, and their sensitivity and negative predictive value were the highest among these methods in the training cohort. In addition, the new models showed good sensitivity and accuracy for the diagnosis of LRF impairment in the validation cohort.The new models had a good predictive performance for LRF and could replace the indocyanine green (ICG) clearance test, especially in patients who are unable to undergo ICG testing.

MicroRNAs (miRNAs) act as regulators of plant development and multiple stress responses. Here we demonstrate that the rice miR171b-SCL6-IIs module regulates the balance between blast resistance, grain yield, and flowering. miR171b-overexpressing rice plants (OX171b) displayed increased rice blast resistance accompanied with enhanced defense responses and late heading, whereas blocking miR171b expression in rice (MIM171) led to greater susceptibility to blast disease, associated with compromised defense responses and early heading. Either overexpressing or silencing of miR171b significantly affected plant height and number of filled seeds per panicle (seed-setting rate), resulting in decreased grain yield. miR171b targets SCL6-IIa, SCL6-IIb, and SCL6-IIc, whose expression was suppressed in OX171b but increased in MIM171. Mutants of SCL6-IIa, SCL6-IIb, and SCL6-IIc all displayed phenotypes like that of OX171b, including markedly increased blast disease resistance, slightly decreased grain yield, and delayed flowering. Amounts of miR171b increased gradually in leaves during the vegetative stage but decreased gradually in panicles during the reproductive stage, whereas SCL6-IIs displayed the reverse expression pattern. Together, these results suggest that the expression of miR171b was time- and space-dependent during the rice growth period and regulated the balance between rice blast disease resistance, grain yield, and flowering via SCL6-IIs, and that appropriate accumulation of miR171b is essential for rice development.

BackgroundSympathetically maintained pain (SMP) involves an increased excitability of dorsal root ganglion (DRG) neurons to sympathetic nerve stimulation and circulating norepinephrine. The current treatment of SMP has limited efficacy, and hence more mechanistic insights into this intractable pain condition are urgently needed.MethodsA caudal trunk transection (CTT) model of neuropathic pain was established in mice.Immunofluorescence staining, small interfering RNA, pharmacological and electrophysiological studies were conducted to test the hypothesis that norepinephrine increases the excitability of small-diameter DRG neurons from CTT mice through the activation of cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) signaling pathway.ResultsBehavior study showed that CTT mice developed mechanical and heat hypersensitivities, which were attenuated by intraperitoneal injection of guanethidine. CTT mice also showed an abnormal sprouting of tyrosine hydroxylase-positive nerve fibers in DRG, and an increased excitability of small-diameter DRG neurons to norepinephrine, suggesting that CTT is a useful model to study SMP. Importantly, inhibiting cGMP-PKG pathway with small interfering RNA and KT5823 attenuated the increased sympathetic sensitivity in CTT mice. In contrast, cGMP activators (Sp-cGMP, 8-Br-cGMP) further increased sympathetic sensitivity. Furthermore, phosphorylation of ATP-sensitive potassium channel, which is a downstream target of PKG, may contribute to the adrenergic modulation of DRG neuron excitability.ConclusionsOur findings suggest an important role of cGMP-PKG signaling pathway in the increased excitability of small-diameter DRG neurons to norepinephrine after CTT, which involves an inhibition of the ATP-sensitive potassium currents through PKG-induced phosphorylation. Accordingly, drugs targeting this pathway may help to treat SMP.

With the soaring number of multidrug-resistant bacteria, it is imperative to develop novel efficient antibacterial agents and discovery new antibacterial pathways. Herein, we designed and synthesized a series of structurally novel glycyrrhetinic acid (GA) derivatives against multidrug-resistant Staphylococcus aureus (MRSA). The in vitro antibacterial activity of these compounds was evaluated using the microbroth dilution method, agar plate coating experiments and real-time growth curves, respectively. Most of the target derivatives showed moderate antibacterial activity against Staphylococcus aureus (S. aureus) and MRSA (MIC = 3.125-25 μM), but inactivity against Escherichia coli (E. Coli) and Pseudomonas aeruginosa (P. aeruginosa) (MIC 200 μM). Among them, compound 11 had the strongest antibacterial activity against MRSA, with an MIC value of 3.125 μM, which was 32 times and 64 times than the first-line antibiotics penicillin and norfloxacin, respectively. Additionally, transcriptomic (RNA-seq) and quantitative polymerase chain reaction (qPCR) analysis revealed that the antibacterial mechanism of compound 11 was through blocking the arginine biosynthesis and metabolic and the H

The receptor-like kinase (RLK) FERONIA functions in immunity in Arabidopsis. Here, we systemically screened rice RLK genes encoding FERONIA-like receptor (FLRs) that may be involved in rice-Magnaporthe oryzae interaction. The expression of 16 FLR genes was examined in response to the infection of M. oryzae in different rice varieties. For each FLR gene, at least two independent mutants were generated by CRISPR/Cas9 gene-editing technology in rice variety Zhonghua 11 (ZH11). Blast disease assay identified that the mutants of FLR1 and FLR13 showed increased susceptibility, whereas the mutants of FLR2 and FLR11 displayed enhanced resistance. Consistently, the mutant of FLR1 enhanced, but the mutant of FLR2 delayed the M. oryzae infection progress, which might be associated with the altered expression of defense-related genes. Together, these data indicate that at least 4 FLR genes are involved in rice-M. oryzae interaction and thus are potentially valuable in blast disease resistance.

The performances of routine tests such as FIB-4 and APRI in detecting cirrhosis and significant fibrosis in chronic hepatitis B (CHB) have been shown to be discrepant between studies. Novel tests such as red cell distribution width-platelet ratio (RPR), γ-glutamyl transpeptidase to platelet ratio (GPR) and easy liver fibrosis test (eLIFT) are introduced recently. To evaluate the aminotransferase influence on the performance of these routine tests, a total of 1005 CHB patients who underwent liver biopsies and routine tests were retrospectively analysed. The diagnostic cut-offs referring to likelihood ratio were determined for excluding or including cirrhosis diagnosis and also for ruling in significant fibrosis diagnosis. The performances of RPR, FIB-4, eLIFT and APRI in detecting cirrhosis seemed improved at higher ALT levels, while GPR was conversely impaired. The likelihood ratio was ∝ for APRI cut-off 2 diagnosing cirrhosis in ALT < 2 upper limit of normal (ULN), 14.6 for APRI cut-off 1.5 determining significant fibrosis in ALT ≤ 5ULN and 20.6 for FIB-4 cut-off 3.2 diagnosing ≥ F3 in the total cohort, respectively. The optimal cut-offs for cirrhosis diagnosis were increased with higher ALTs by tests which included aminotransferase, but not for RPR. The proportions of patients classified as having cirrhosis or no cirrhosis stratified by ALT level cut-offs were superior. Stepwise applying RPR, GPR and eLIFT would determine 60% of patients as having cirrhosis or no cirrhosis with an accuracy of 93.0%. In conclusion, the performance of aminotransferase comprising tests in detecting cirrhosis in CHB were influenced by ALT levels. Thus, ALT stratified cut-offs may be a preferred alternative. In resource-limited settings, stepwise applying routine tests could be recommended as a preferred measurement for cirrhosis detection.

Cryptosporidium spp. and Enterocytozoon bieneusi (E. bieneusi) are two common opportunistic pathogens that can infect humans and animals worldwide. The available data on the prevalence of these pathogens is insufficient in Hebei Province, China, which is located in the Bohai Sea region. In the present study, 718 fecal specimens of native beef cattle from eight farms in Hebei Province were examined for the presence of Cryptosporidium spp. and E. bieneusi using nested PCR targeting the small subunit (SSU) rRNA gene of Cryptosporidium spp. and the internal transcribed spacer (ITS) of E. bieneusi. The prevalence of Cryptosporidium spp. was 9.2% (66/718) and E. bieneusi was 8.6% (62/718). C. andersoni (n = 56) and C. parvum (n = 10) were identified in this study, and all C. parvum-positive specimens belonged to IIdA20G1 in the gp60 gene. The ITS sequence analysis obtained seven known E. bieneusi genotypes, including J (n = 48), BEB4 (n = 4), CHC8 (n = 3), EbpC (n = 2), I (n = 2), D (n = 2), and BEB6 (n = 1). Genotype D and EbpC belonged to the zoonotic Group 1, while the other genotype belonged to the host-adapted Group 2. This is the first report on the occurrence of E. bieneusi in beef cattle in Hebei Province. In this study, the presence of zoonotic C. parvum and two E. bieneusi genotypes suggest that cattle can be a potential zoonotic source for human or animal infection.

During the COVID-19 lockdown, atmospheric PM

To evaluate the efficiency of ultrasonic spleen thickness (UST), routine variables and (expanded) Baveno VI criteria for high-risk gastroesophageal varices (HRGOV) detection in cirrhotic patients.In total, 305 cirrhotic patients were retrospectively enrolled in the deriving cohort and 328 cirrhotic patients with hepatitis B sustained viral response were prospectively enrolled in the validation cohort. HRGOV was defined as medium and severe gastroesophageal varices (GOV), mild GOV with red signs or Child-Pugh C. The cut-offs for HRGOV were determined by likelihood ratio indicating strong evidences. Algorithms of Spleen thickness-Age-Liver stiffness measurement (LSM, by FibroscanThe area under receiver operating characteristics curve of SALA, SPA, UST, platelet, and LSM were 0.849, 0.835, 0.808, 0.746, and 0.655 in the deriving cohort, and improved to 0.901, 0.904, 0.858, 0.876, and 0.811 in the validation cohort, respectively. While SALA, SPA, UST, platelet, Baveno VI criteria (BVI), and expanded BVI spared 46.6%, 38.0%, 29.2%, 21.0%, 12.1%, and 23.6% esophagogastroduodenoscopy in the deriving cohort, these numbers were improved to 68.1%, 66.8%, 27.1%, 37.8%, 36.0%, and 61.0% in the validating cohort, respectively; however, the negative likelihood ratio of expanded BVI was up to 0.16. SPA spared less esophagogastroduodenoscopy than SALA, which can be supplemented by stepwise applying UST and SPA. Sequentially combining UST and SALA, BVI and SALA exempted additional 10-5% endoscopies.SPA, without LSM, improves HRGOV detection comparing with BVI. UST based algorithms combination can achieve the best efficiency especially in sustained virus response hepatitis B.

Magnaporthe oryzae is the causative agent of rice blast, a devastating disease in rice worldwide. Based on the gene-for-gene paradigm, resistance (R) proteins can recognize their cognate avirulence (AVR) effectors to activate effector-triggered immunity. AVR genes have been demonstrated to evolve rapidly, leading to breakdown of the cognate resistance genes. Therefore, understanding the variation of AVR genes is essential to the deployment of resistant cultivars harboring the cognate R genes. In this study, we analyzed the nucleotide sequence polymorphisms of eight known AVR genes, namely, AVR-Pita1, AVR-Pii, AVR-Pia, AVR-Pik, AVR-Pizt, AVR-Pi9, AVR-Pib, and AVR-Pi54 in a total of 383 isolates from 13 prefectures in the Sichuan Basin. We detected the presence of AVR-Pik, AVR-Pi54, AVR-Pizt, AVR-Pi9, and AVR-Pib in the isolates of all the prefectures, but not AVR-Pita1, AVR-Pii, and AVR-Pia in at least seven prefectures, indicating loss of the three AVRs. We also detected insertions of Pot3, Mg-SINE, and indels in AVR-Pib, solo-LTR of Inago2 in AVR-Pizt, and gene duplications in AVR-Pik. Consistently, the isolates that did not harboring AVR-Pia were virulent to IRBLa-A, the monogenic line containing Pia, and the isolates with variants of AVR-Pib and AVR-Pizt were virulent to IRBLb-B and IRBLzt-t, the monogenic lines harboring Pib and Piz-t, respectively, indicating breakdown of resistance by the loss and variations of the avirulence genes. Therefore, the use of blast resistance genes should be alarmed by the loss and nature variations of avirulence genes in the blast fungal population in the Sichuan Basin.

MicroRNAs fine-tune plant growth and resistance against multiple biotic and abiotic stresses. The trade-off between biomass and resistance can penalize crop yield. In this study, we have shown that rice miR530 regulates blast disease resistance, yield, and growth period. While the overexpression of miR530 results in compromised blast disease resistance, reduced grain yield, and late maturity, blocking miR530 using a target mimic (MIM530) leads to enhanced resistance, increased grain yield, and early maturity. Further study revealed that the accumulation of miR530 was decreased in both leaves and panicles along with the increase of age. Such expression patterns were accordant with the enhanced resistance from seedlings to adult plants, and the grain development from panicle formation to fully-filled seeds. Divergence analysis of miR530 precursor with upstream 1,000-bp promoter sequence in 11 rice species revealed that miR530 was diverse in Oryza sativa japonica and O. sativa indica group, which was consistent with the different accumulation of miR530 in japonica accessions and indica accessions. Altogether, our results indicate that miR530 coordinates rice resistance, yield, and maturity, thus providing a potential regulatory module for breeding programs aiming to improve yield and disease resistance.

OBJECTIVE: To study the application of ponderal index (PI), body mass index (BMI), mid-arm circumference/head circumference (MAC/HC), and Clinical Assessment of Nutritional Status (CANS) score in assessing the nutritional status of neonates at birth, and to find a simple and reliable scheme for the assessment of fetal nutritional status. METHODS: PI, BMI, MAC/HC, and CANS were used to assess the nutritional status of full-term infants and preterm infants shortly after birth. The assessment results of these methods were analyzed. RESULTS: Among the 678 full-term infants, 61, 102, 47, and 131 were diagnosed with malnutrition by PI, BMI, MAC/HC, and CANS respectively. Among the 140 preterm infants, 30, 87, 9, and 112 were diagnosed with malnutrition by PI, BMI, MAC/HC, and CANS respectively. The combination of BMI and CANS had a detection rate of 99.3% in full-term infants and 100% in preterm infants. Compared with the single method, the combination significantly improved the detection rate of malnutrition (P < 0.05), while there was no significant difference between the combination of BMI+CANS and the combination of PI+BMI+CANS (P > 0.05). CONCLUSIONS: The combination of BMI+CANS can reduce the rate of missed diagnosis of fetal malnutrition. It is therefore a simple and reliable method for the assessment of fetal malnutrition.

We read with interest the recent article by Cai et al 1 describing the development of 5-hydroxymethylcytosine (5hmC)-based wd-scores that have better accuracy in diagnosing early hepatocellular carcinoma (HCC) than does α-fetoprotein (AFP). Although several gene signatures have been published but not used in practice of early HCC diagnosis,2 this study showed the potential application of the 5hmC-based wd scores. However, several concerns remain that need to be clarified. First, the wd-scores’ cut-off for early diagnosis of HCC, derived by the maximal Youden index and characterised by a sensitivity of 82.7% and a specificity of 76.4%, is suboptimal; this would result in missed diagnosis of early HCC in 17.3% of patients, and the corresponding …

For the problem that information disorder and additional noises, as well as the instability of formation control in a massive-group-robot system, stops the system from achieving a good convergence state, a control algorithm based on the weight matrix stability of Kalman filtering is proposed. Through a robustness and uncertainty analysis, the uncertainty in information exchange in robots is transformed into an uncertain factor in nonlinear system. The Kalman filter helps to realize the convergent consistency of ideal state of robot system. The validity of this algorithm is proved by experiments.

In order to solve the problems in the high computation, mono moving direction, low real time effect when switching gaits and unstable switching steps, etc., a fast computing method for omnidirectional motion planning of humanoid robot is proposed. The motion planning based on module design helps to obtain the moving trajectories in directions and the direction-switching algorithm based on one of multiple steps of segments helps to interconnect directional movements and realize the stability and fluency. The validity of method is proved by experiments.

Vehicle terminal can upload the vehicle status information to the server in time, to provide service for the users with more security. But vehicle terminal in the process of upload information to the server need to solve many issues, such as a large number of terminals connecting to the server, large amount of data, the data of transmission in various forms, the server is not stable enough and many other issues. This design uses the Hypertext Transfer Protocol (HTTP) to achieve reliable data transmission between the WEB server and vehicle terminals, and the load of server is lower, so the server can support more vehicle terminals’ connection.

Statement of problem The introduction of polymer-infiltrated ceramic network (PICN) materials may provide more options for dentists in restoring short clinical crowns and extensively damaged posterior teeth, but clinical data for their performance are lacking. Purpose The purpose of this clinical study was to compare the 3-year performance and survival rates of PICN material with those of conservative ceramic onlay restorations for endodontically treated posterior teeth using the CEREC AC chair-side system. Material and methods A total of 101 onlay restorations of endodontically treated posterior teeth using the CEREC AC chair-side system were provided in 93 participants. The 101 teeth were divided into 2 groups: Vita Enamic group and Vitablocs Mark II group. Using the modified US Public Health Service quality evaluation system, 2 calibrated evaluators examined the performance of the onlay restorations over 3 years. The Kaplan-Meier method was adopted to analyze the survival rate of restorations (α=.05). The log rank test was used to compare the survival rates of the 2 groups. The Fisher exact test was performed to detect differences in the success rates for extensively damaged teeth and short clinical crown restorations between the 2 groups. The Silness and Loe gingival index was also recorded. Results The restoration survival rates in the 2 groups were 97.0% (Vita Enamic) and 90.7% (Vitablocs Mark II) (P>.05). Five failures were recorded (4.95%). These failures were caused by restoration debonding (60%), ceramic fractures (20%), and tooth fractures (20%). There were no significant differences between the success rates of restoring extensively damaged teeth and short clinical crowns between the 2 groups (P>.05). The periodontal condition of 25% of participants was improved 3 years after the onlay restorations. Conclusions Onlay restorations of endodontically treated posterior teeth with Vita Enamic using the CEREC AC chair-side system are clinically promising prosthodontic alternatives, with a survival rate of 97.0% after 3 years. More research is needed to verify the results of this study.

Saline intrusion is important for ecological reasons as well as water extraction purposes in estuaries. The distance of saline intrusion depends on a number of factors, including river discharge, tidal and wind mixing and gravitational circulation. In this paper, a simple and effective prediction model is derived for the saline intrusion at high slack water in a well mixed, funnel-shaped estuary whose cross-sectional area decreases exponentially (with convergence length a) with distance, x, inland. The model study shows that a graph of salinity against exp (x/a-1) is a straight line, with the slope proportional to the mixing coefficient Dx. The prediction model is presented and validated in Modaomen estuary, one of estuaries of Pearl River Delta in south China and the model results are compared, with good agreement, to the measured data. By analyzing the relationship between the salt intrusion length and tidal range, it is concluded that the optimal time of increasing runoff discharge to prevent saline intrusion is 2 to 3 days before neap tide.

A series of 4-aryl-hexahydroquinolines were prepared by Hantzsch reaction using aromatic aldehydes obtained from lignin, 1,3-cyclohexanediones, β-ketoesters and ammonium carbonate. The antioxidant properties of compounds 5a-c and 5g-i were evaluated by two methods: scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and scavenging effect on 2,2′-azino-bis(3-ethylenzothiazoline-sulfonic acid) diammonium salt (ABTS + ) radical. The results show that the compounds containing a methoxy moiety exhibit good activities. The study suggests that some synthesized compounds may serve as promising leads for the treatment against tumors or other free radical-related diseases.

Objective Prior studies have reported that blood pressure (BP) has a significant influence on retinal vascular caliber both in adults and children aged 6 years and older. This study aimed to examine the association between BP and retinal vascular caliber in Singapore Chinese preschoolers 4 to 5 years of age. Design Population-based, cross-sectional study. Participants A total of 385 eligible and healthy Singapore Chinese children 4 to 5 years of age who were recruited in The Strabismus, Amblyopia and Refractive Error Study in Singaporean Chinese Preschoolers from May 2006 through October 2008 underwent BP measurements and retinal photography. Methods According to standard protocols, BP was measured with an automatic Omron sphygmomanometer (Omron HEM 705 LP, Omron Healthcare, Inc., Bannockburn, IL) and a retinal photograph was obtained with a Canon 45° digital retinal camera (Model CR6-NM45, Canon, Inc., Tokyo, Japan) after pupil dilation. Anthropometric and optical biometric measurements such as height, weight, and axial length were obtained also. Information regarding sociodemographic status and child birth information was supplied by parents in either English or Chinese questionnaires. Main Outcome Measures The computer imaging program was used to measure the caliber of all retinal arterioles and venules located in zone B. The central retinal arteriolar equivalent and central retinal venular equivalent were estimated by using a revised Knudtson-Parr-Hubbard formula. Results The mean retinal arteriolar and venular calibers were 156.19 μm and 220.01 μm in boys and 161.97 μm and 224.22 μm in girls. Higher systolic BP was associated with narrower retinal arterioles. After adjusting for age, gender, father's education, body mass index, birth weight, axial length, and caliber of the fellow retinal vessel, each 10-mmHg increase in systolic BP was associated with 2.00 μm (95% confidence interval, 0.39–3.61; P = 0.02) of retinal arteriolar narrowing and 2.51 μm (95% confidence interval, 0.35–4.68; P = 0.02) of retinal venular widening. However, neither diastolic BP nor mean arterial BP was associated with retinal arteriolar or venular caliber. Conclusions In very young children 4 to 5 years of age, higher systolic BP was associated with narrower retinal arterioles and wider retinal venules. This suggests that elevated BP may affect the retinal microvasculature from early childhood. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Found in neurons and neuroblastoma cells, Fas-induced apoptosis and accompanied activation of NF-κB signaling were thought to be associated with neurodegenerative diseases. However, the detailed functions of NF-κB activation in Fas killing and the effect of NF-κB activation on its downstream events remain unclear. Here, we demonstrated that agonistic Fas antibody induces cell death in a dose-dependent way and NF-κB signaling is activated as well, in neuroblastoma cells SH-EP1. Unexpectedly, NF-κB activation was shown to be pro-apoptotic, as suggested by the reduction of Fas-induced cell death with either a dominant negative form of IκBα (DN-IκBα) or an IκB kinase-specific inhibitor. To our interest, when analyzing downstream events of NF-κB signaling, we found that DN-IκBα only suppressed the expression of caspase-4, but not other caspases. Vice versa, enhancement of NF-κB activity by p65 (RelA) overexpression increased the expression of caspase-4 at both mRNA and protein levels. More directly, results from dual luciferase reporter assay demonstrated the regulation of caspase-4 promoter activity by NF-κB. When caspase-4 activity was blocked by its dominant negative (DN) form, Fas-induced cell death was substantially reduced. Consistently, the cleavage of PARP and caspase-3 induced by Fas was also reduced. In contrast, the cleavage of caspase-8 remained unaffected in caspase-4 DN cells, although caspase-8 inhibitor could rescue Fas-induced cell death. Collectively, these data suggest that caspase-4 activity is required for Fas-induced cell apoptosis and caspase-4 may act upstream of PARP and caspase-3 and downstream of caspase-8. Overall, we demonstrate that NF-κB can mediate Fas-induced apoptosis through caspase-4 protease, indicating that caspase-4 is a new mediator of NF-κB pro-apoptotic pathway in neuroblastoma cells.

Based on high sequence homology, there are six members in the caspase-1 subfamily: caspases 1, 4, 5, and 13 in humans and caspases 1, 11, and 12 in mice. Only caspase-1 is known to activate interleukin-1beta and interleukin-18, and caspase-11 activates pro-caspase-1 in vivo. Almost nothing is known about caspases 4, 5, and 13. Here we report a sensitive and specific polymerase chain reaction system to analyze closely related genes. We employed this system to analyze the gene expression and regulation of human caspases 1, 4, 5, and 13, demonstrating that they have different expression patterns in normal tissues and cell lines. Interferon-gamma strongly induced CASP1 and CASP5 but not CASP4 or CASP13 gene expression in HT-29 colon carcinoma cells. In contrast to the mRNA, interferon-gamma up-regulated caspase-1 but not caspase-5 protein. In the monocytic cell line THP-1, CASP1 mRNA and caspase-1 protein are expressed constitutively, and their levels were not increased by lipopolysaccharide, whereas both CASP5 mRNA and caspase-5 protein were induced by lipopolysaccharide. Caspase-1 subfamily members displayed different in vitro activities toward pro-caspases 1 and 3 and pro-interleukin-1beta. Our results demonstrate that caspase-1 and caspase-5 levels are modulated by interferon-gamma and lipopolysaccharide, respectively, and suggest that caspase-1 subfamily members are differentially regulated and may have distinct functions.

Purpose: An association between birth order and reduced unaided vision (a surrogate for myopia) has been observed previously. We examined the association between birth order and myopia directly in four subject groups. Methods: Subject groups were participants in (1) the Avon Longitudinal Study of Parents and Children (ALSPAC; UK; age 15 years; N = 4401), (2) the Singapore Cohort Study of Risk Factors for Myopia (SCORM; Singapore; age 13 years; N = 1959), (3) the Raine Eye Health Study (REHS; Australia; age 20 years; N = 1344), and (4) Israeli Defense Force Pre-recruitment Candidates (IDFC; Israel; age 16–22 years; N = 888,277). The main outcome was odds ratios (OR) for myopia in first-born versus non-first-born individuals after adjusting for potential risk factors. Results: The prevalence of myopia was numerically higher in first-born versus non-first-born individuals in all study groups, but the strength of evidence varied widely. Adjusted ORs (95% confidence intervals, CIs) were: ALSPAC, 1.31 (1.05–1.64); SCORM, 1.25 (0.89–1.77); REHS, 1.18 (0.90–1.55); and IDFC, 1.04 (1.03–1.06). In the large IDFC sample, the effect size was greater (a) for the first-born versus fourth- or higher-born comparison than for the first-born versus second/third-born comparison (p

To determine the risk factors for strabismus and amblyopia in young Singapore Chinese children.A total of 3009 children were recruited for the population-based cross-sectional Strabismus, Amblyopia and Refractive Error in Singaporean Preschoolers Study (STARS). Strabismus was defined as any tropia identified on cover test. Visual acuity was measured in children aged 30-72 months with a logMAR chart where possible and the Sheridan-Gardiner test if not. Amblyopia was defined based on visual acuity and refractive error or presence of strabismus or past/present visual axis obstruction. Parents completed questionnaires on family, prenatal and birth histories.Our study showed that 24 children aged 6-72 months (1.2%) had strabismus (20 with exotropia), and 20 children aged 30-72 months (0.8%) were amblyopic. After multivariate analysis, strabismus was associated with astigmatism ≥1.00 diopter (D; p = 0.03), amblyopia (p = 0.003), a sibling with strabismus (p 0.001), and families with lower parental education (p = 0.04). In addition to strabismus, amblyopia was associated with anisometropia ≥1.00 D (p 0.001) and astigmatism ≥1.00 D (p 0.001). No association was noted between either strabismus or amblyopia and prematurity, maternal age or smoking.This study highlights the importance of family history in strabismus, and the close associations between refractive error and strabismus with amblyopia. These factors play a more important role in young Singapore Chinese children.

Interleukin 1beta-converting enzyme-like (ICE-like) proteases are important mediators of apoptosis in diverse cell types and organisms. However, the role of these proteases in apoptosis cannot be satisfactorily explained on the basis of the physiological functions of their known substrates. Here we show that the C-terminal 42 amino acid peptide of the retinoblastoma (Rb) protein, an important cell cycle regulator with a known anti-apoptotic function, is specifically cleaved off by an ICE-like protease in tumour necrosis factor (TNF)- and staurosporine-induced apoptosis. Cleavage of Rb induced by TNF was blocked in vivo and in vitro by two specific inhibitors of ICE-like proteases, and in vitro by a point mutation (Asp886 to Ala) within the ICE-like protease cleavage site of Rb, (883)DEAD(886). An antibody raised against the C-terminal 15 amino acid peptide of Rb recognized the full-length but not the cleaved form of Rb. The extent of Rb cleavage correlated directly with TNF-induced apoptosis in all tumour cell lines examined. Cleaved Rb bound cyclin D3 and inhibited the transcriptional activity of E2F-1, but failed to bind to the regulatory protein MDM2, which has been implicated in apoptosis. As Rb suppresses cell death and its C-terminus has important regulatory functions, our results suggest that Rb cleavage is an important event in apoptosis.

c-Myc is an important mediator of apoptosis in cytokine- or serum-deprived cells and sensitizes various cell types to tumor necrosis factor alpha (TNF) cytotoxicity. However, downstream mediators of c-Myc-dependent apoptosis are largely unknown. In this study, we investigated whether one or more cyclins which, like c-Myc, are important regulators of the cell cycle are involved in TNF-induced apoptosis downstream of c-Myc. Cyclin D3 and c-Myc levels in HeLa and fibrosarcoma cells correlated with sensitivity of these cells to TNF-induced apoptosis, as both proteins were highly expressed in TNF-sensitive HeLa D98 cells and HT-1080 fibrosarcoma cells but not in their TNF-resistant counterparts, HeLa H21 and SS-HT-1080 cells, respectively. All other cyclins tested were equally expressed in all tumor cell lines. Reduction in the expression of c-Myc by dexamethasone or inhibition of the transcriptional activity of c-Myc by introduction of a dominant negative form of c-Myc into TNF-sensitive HeLa D98 cells strongly suppressed the expression of cyclin D3 (but none of the other cyclins) and rendered the cells resistant to TNF-induced apoptosis. Conversely, introduction of the c-myc gene into TNF-resistant, c-Myc- and cyclin D3-deficient HeLa H21 cells resulted in enhanced cyclin D3 expression and TNF killing. When cyclin D3 expression in HeLa cells was altered by sense or antisense cyclin D3 cDNA, there was a concomitant alteration in their susceptibility to TNF-induced apoptosis without any change in c-Myc levels. Overall, our results show that cyclin D3 sensitizes tumor cells to TNF-induced apoptosis and indicate that the expression of c-Myc and expression of cyclin D3 in HeLa and in HT-1080 fibrosarcoma cells are closely linked.

The respiratory burst is dependent on a source of glucose. We wished to investigate the effect of glucose on the superoxide production of circulating neutrophils. Superoxide production of neutrophils was significantly enhanced by glucose concentration of from 1 to 50 mmole/liter in the medium. The neutrophils from asthmatics in both the acute and remission phases showed greater production of superoxide than those of controls. When the neutrophils were made to undergo the respiratory burst, initially in the absence of glucose, and thereafter in the presence of 5 and 20 mmole/liter glucose, the rate of superoxide formation with higher glucose medium was decreased in the control cells but significantly increased in the cells of the acute asthmatics in remission. It is concluded that glucose as an energy source is potentially critical in determining the rate of the respiratory burst and that the neutrophils from asthmatic subjects in some way have an enhanced uptake or metabolism of this substrate. Glycemic status may then have some role in determining the amount of superoxide production, and therefore airway inflammation, in asthma.

PURPOSE. We aimed to determine the relationship between puberty and growth spurts with peak spherical equivalent (SE) or axial length (AL) velocity in Singapore schoolchildren. METHODS. In the Singapore Cohort Study of the Risk Factors for Myopia of 1779 schoolchildren, the longitudinal refractive and pubertal status of 892 boys and 887 girls from ages 6 to 14 years were assessed. The study sample included 1329 Chinese, 316 Malays, 114 Indians, and 20 children of other races. Information regarding puberty parameters, age of peak height velocity, age of menarche, and break of voice (BOV) was obtained. Peak velocity was defined as the greatest change in measurements over a period of 1 year. Tanner stage 1 for pubic hair or breast development, in boys and girls, respectively, at age 12 was categorized as ‘‘later puberty,’’ whereas stages 2 to 5 corresponded to ‘‘earlier puberty.’’ Refractive error was determined by cycloplegic autorefraction using the Canon RK-F5, and AL was measured using the A-scan biometry machine. RESULTS. The children were examined annually, and the mean number of visits was 5.7 6 1.3. Age of peak height velocity occurred earlier in girls than in boys (11.0 6 1.2 vs. 12.0 6 1.7 years, P < 0.001). Girls with earlier peak height velocity experienced peak AL velocity and peak SE velocity approximately half a year earlier than those with later puberty (mean age of 10.3 6 1.6 vs. 10.8 6 1.7 years, P < 0.001; and 10.0 6 1.5 vs. 10.6 6 1.25 years, P < 0.001, respectively). Similarly, boys who had earlier peak height velocity also achieved peak AL and peak SE velocity earlier than those who experienced later peak height velocity (mean age of 10.4 6 1.6 vs. 11.1 6 1.8 years, P < 0.001; and 10.1 6 1.5 vs. 10.6 6 1.7 years, P ¼ 0.01). Both girls and boys who had early peak height velocity had earlier age of onset of myopia than those with later peak height velocity (9.7 6 1.4 vs. 10.1 6 1.5 years for girls, P ¼ 0.04; and 9.9 6 1.5 vs. 10.4 6 1.6 years for boys, P ¼ 0.03). Myopia progression, in terms of AL velocity, also occurred earlier in boys and girls with earlier peak height velocity (10.2 6 1.5 vs. 11.0 6 1.9 for boys, P < 0.001; and 10.2 6 1.5 vs. 10.7 6 1.7 for girls, P ¼ 0.004, respectively). The associations were not significant when Tanner staging, age of menarche, or BOV was used to determine stage of puberty. CONCLUSIONS. Boys and girls with earlier peak height velocity experienced earlier peak SE and AL velocity, and age of myopia onset. Thus, variations in the onset and peak progression of myopia may be associated with height spurts. (Invest Ophthalmol Vis Sci. 2012;53:7961–7966) DOI:10.1167/ iovs.12-10402

To examine the pattern of myopia-related macular and optic disc changes in Singapore adults with high myopia (spherical equivalent ≤-6.00 diopters).Asian adults with high myopia from 3 population-based surveys.Adults 40 years and older (n = 359) with high myopia were pooled from 3 population-based surveys in Singapore Asians: (1) the Singapore Prospective Study Program (SP2, n = 184); (2) the Singapore Malay Eye Study (SiMES, n = 98); and (3) the Singapore Indian Eye Study (SINDI, n = 77). All study participants underwent standardized refraction and fundus photography, and SiMES and SINDI subjects also completed ocular biometry measurements. Myopia-related macular (posterior staphyloma, lacquer cracks, Fuchs spot, myopic chorioretinal atrophy, and myopic choroidal neovascularization) and optic disc (optic nerve head tilt, optic disc dimensions, and peripapillary atrophy) changes were evaluated.The most common myopia-related macular finding in adults with high myopia was staphyloma (23%), followed by chorioretinal atrophy (19.3%). There were few cases of lacquer crack (n = 6, 1.8%), T-sign (n = 6, 1.8%), retinal hemorrhage (n = 3, 0.9%), active myopic choroidal neovascularization (n = 3, 0.9%), and no case of Fuchs spot. The most common disc finding associated with high myopia was peripapillary atrophy (81.2%), followed by disc tilt (57.4%). Staphyloma and chorioretinal atrophy increased in prevalence with increasing age, increasing myopic refractive error, and increasing axial length (all P.001). Ethnicity comparisons demonstrated the highest proportion of staphyloma (P = .04) among Malays, the highest proportion of peripapillary atrophy (P = .01) and disc tilt (P.001) among Chinese, and the largest cup-to-disc ratio (P .001) among Indians.Staphyloma and chorioretinal atrophy lesions were the most common fundus findings among Asian adults with high myopia. In this population, tilted discs and peripapillary atrophy were also common, while choroidal neovascularization and Fuchs spot were rare. In contrast with Singapore teenagers, in whom tilted disc and peripapillary atrophy were common while staphyloma and chorioretinal atrophy were rare, pathologic myopia appears to be dependent on the duration of disease and, thus, age of the individual.

As sciatica and low back pain are among the most common medical complaints, many studies have duplicated these conditions in animals. Chronic compression of the dorsal root ganglion (CCD) is one of these models. The surgery is simple: after exposing the L4/L5 intervertebral foramina, stainless steel rods are implanted unilaterally, one rod for each vertebra, to chronically compress the lumbar dorsal root ganglion (DRG). Then, CCD can be used to simulate the clinical conditions caused by stenosis, such as a laterally herniated disc or foraminal stenosis. As the intraforaminal implantation of a rod results in neuronal somal hyperexcitability and spontaneous action potentials associated with hyperalgesia, spontaneous pain, and mechanical allodynia, CCD provides an animal model that mimics radicular pain in humans. This review concerns the mechanisms of neuronal hyperexcitability, focusing on various patterns of spontaneous discharge including one possible pain signal for mechanical allodynia — evoked bursting. Also, new data regarding its significant property of maintaining peripheral input are also discussed. Investigations using this animal model will enhance our understanding of the neural mechanisms for low back pain and sciatica. Furthermore, the peripheral location of the DRG facilitates its use as a locus for controlling pain with minimal central effects, in the hope of ultimately uncovering analgesics that block neuropathic pain without influencing physiological pain.