The central circadian pacemaker, the suprachiasmatic nucleus (SCN), encodes day length information by mechanisms that are not well understood. Here, we report that genetic ablation of miR-132/212 ...alters entrainment to different day lengths and non-24 hr day-night cycles, as well as photoperiodic regulation of Period2 expression in the SCN. SCN neurons from miR-132/212-deficient mice have significantly reduced dendritic spine density, along with altered methyl CpG-binding protein (MeCP2) rhythms. In Syrian hamsters, a model seasonal rodent, day length regulates spine density on SCN neurons in a melatonin-independent manner, as well as expression of miR-132, miR-212, and their direct target, MeCP2. Genetic disruption of Mecp2 fully restores the level of dendritic spines of miR-132/212-deficient SCN neurons. Our results reveal that, by regulating the dendritic structure of SCN neurons through a MeCP2-dependent mechanism, miR-132/212 affects the capacity of the SCN to encode seasonal time.
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•miR-132/212 modulates entrainment to seasonal photoperiods•Ablation of miR-132/212 reduces dendritic spine density of SCN clock neurons•Photoperiod regulates miR-132/212 expression and dendritic morphology in hamsters•miR-132/212 acts through MeCP2, and downstream BDNF and mTOR are involved
Seasonal adaptation is believed to require plasticity in the SCN, although the mechanisms are unclear. Mendoza-Viveros et al. report that miR-132/212 modulates dendritic protrusion density and photoperiodic adaptation in mice and hamsters, by regulating the expression of MeCP2, and downstream BDNF and mTOR signaling.
Objectives Emergence of multiresistant Gram-negative organisms in intensive care units (ICUs) throughout the world is a concerning problem. Therefore we undertook a study to follow the resistance ...patterns of the most common clinically isolated Gram-negative organisms within our ICU following an antibiotic stewardship intervention to evaluate whether a reduction in broad-spectrum antibiotics improves local antibiotic resistance patterns. Methods This prospective study was conducted over a 7 year period within an ICU at a tertiary teaching hospital in Melbourne, Australia. All clinically isolated Gram-negative organisms were identified and extracted from the hospital pathology system. Three monthly antibiograms were created. The pre-interventional period occurred between January 2000 and June 2002 (10 quarters) and the post-interventional period was defined from July 2002 to December 2006 (18 quarters). Segmented linear regression was used to analyse for a difference in the rates of change in susceptibility. Results A total of 2838 Gram-negative organisms were isolated from clinical sites from ICU patients during the study period. There was significant improvement in susceptibility of Pseudomonas to imipenem 18.3%/year 95% confidence interval (CI): 4.9–31.6; P = 0.009 and gentamicin 11.6%/year (95% CI: 1.8–21.5; P = 0.02) compared with the pre-intervention trend. Significant changes in the rates of gentamicin and ciprofloxacin susceptibility were also observed in the inducible Enterobacteriaceae group although these were less clinically significant. Conclusions This study demonstrates improved antibiotic susceptibility of ICU Gram-negative isolates including Pseudomonas following an intervention aimed at reducing broad-spectrum antibiotics.
Abstract Purpose To investigate the stability of corneal astigmatism and higher-order aberrations after combined femtosecond-assisted phacoemulsification and arcuate keratotomy. Design Retrospective, ...interventional case series Methods Surgery was performed using VICTUS (Bausch & Lomb Inc, Dornach, Germany) platform. A single, 450-μm deep, arcuate keratotomy was paired at 8 mm zone with the main phacoemulsification incision in the opposite meridian. The keratotomy incisions were not opened. Corneal astigmatism and higher-order aberrations measurements obtained preoperatively, and at 2 months and 2 years postoperatively were analyzed. Results Fifty eyes of 50 patients (mean age 66.2 ± 10.5 years) were included. The mean preoperative corneal astigmatism was 1.35 ± 0.48 diopters (D). This was reduced to 0.67 ± 0.54 D at two months and 0.74 ± 0.53 D at two years postoperatively (p < 0.001). There was no statistically significant difference between postoperative corneal astigmatism over 2 years (p = 0.392). Both magnitude of error and absolute angle of error were comparable between the 2 postoperative time points (p > 0.283). At postoperative 2 months and 2 years, 72% and 70% of eyes were within 15 degrees of preoperative meridian of astigmatism, respectively. All wavefront measurements increased significantly at 2 months and 2 years (p < 0.007), except spherical aberration (p > 0.150). There was no significant difference in higher-order aberrations between 2 months and 2 years postoperatively (p > 0.486). Conclusions Our study showed the stability of femtosecond-assisted arcuate keratotomy. Further studies using other platforms and nomograms are needed to corroborate the findings of this study.
Several studies indicated that tumor thickness or tumor volume might be helpful predictors for the prognosis of oral tongue squamous cell carcinoma. Our aim was to compare the value of tumor ...thickness versus tumor volume measurement based on preoperative MR imaging in predicting the prognosis of oral tongue squamous cell carcinoma, especially focusing on lymph node metastases and local recurrence.
Clinical, pathologic, and imaging data of patients with 46 oral tongue squamous cell carcinomas were retrospectively studied. Logistic regression analysis was used to evaluate the prognostic value of tumor thickness and tumor volume based on MR imaging. Receiver operating characteristic analysis was applied for the optimal cutoff value for the identified risk variable for prognosis.
A higher intraclass correlation coefficient was achieved for the measurement of tumor thickness compared with tumor volume (0.990 versus 0.972). Multivariate analysis showed that tumor thickness was a significant predictor of lymph node metastases (P = .024), while tumor volume was not a significant predictor of either lymph node metastases or local recurrence (P > .05). Receiver operating characteristic results indicated that setting a tumor thickness of 8.5 mm as a cutoff value could achieve the optimal diagnostic efficiency for predicting lymph node metastases (area under the curve, 0.753; sensitivity, 0.889; specificity, 0.536).
Tumor thickness based on preoperative MR imaging was useful in predicting the prognosis of oral tongue squamous cell carcinoma, especially lymph node metastases, in our patient population, while tumor volume was not.
BackgroundRecently, we described the discovery of a novel group 2 coronavirus, coronavirus HKU1 (CoV-HKU1), from a patient with pneumonia. However, the clinical and molecular epidemiological features ...of CoV-HKU1–associated pneumonia are unknown MethodsProspectively collected (during a 12-month period) nasopharyngeal aspirates (NPAs) from patients with community-acquired pneumonia from 4 hospitals were subjected to reverse-transcription polymerase chain reaction, for detection of CoV-HKU1. The epidemiological, clinical, and laboratory characteristics of patients with CoV-HKU1–associated pneumonia were analyzed. The pol spike (S), and nucleocapsid (N) genes were also sequenced ResultsNPAs from 10 (2.4%) of 418 patients with community-acquired pneumonia were found to be positive for CoV-HKU1. All 10 cases occurred in spring and winter. Nine of these patients were adults, and 4 had underlying diseases of the respiratory tract. In the 6 patients from whom serum samples were available, all had a 4-fold change in immunoglobulin (Ig) G titer and/or presence of IgM against CoV-HKU1. The 2 patients who died had significantly lower hemoglobin levels, monocyte counts, albumin levels, and oxygen saturation levels on admission and had more-extensive involvement visible on chest radiographs. Sequence analysis of the pol S, and N genes revealed 2 genotypes of CoV-HKU1 ConclusionsCoV-HKU1 accounts for 2.4% of community-acquired pneumonia, with 2 genotypes in the study population. Without performance of diagnostic tests, the illness was clinically indistinguishable from other community-acquired pneumonia illnesses
To investigate the long-term stability of corneal astigmatism after combined femtosecond (fs)-assisted phacoemulsification and arcuate keratotomy.
Retrospective, interventional case series.
Surgery ...was performed using a Victus (Bausch & Lomb) platform. A single, 450-μm-deep arcuate keratotomy was paired at the 8-mm zone with the main phacoemulsification incision in the opposite meridian. The keratotomy incisions were not opened. Corneal astigmatism measurements obtained preoperatively and at 2 and 5 years postoperatively were analyzed using vector analysis.
A total of 44 eyes of 44 patients (mean age 66.0 ± 10.1 years) were included. The mean preoperative corneal astigmatism was 1.40 ± 0.66 diopters (D). This was reduced to 0.74 ± 0.54 D at 2 years and 0.70 ± 0.50 at 5 years postoperatively (P < .001). There were no statistically significant differences between postoperative corneal astigmatism at 2 years and at 5 years (P = .609). Both magnitude of error and absolute angle of error were comparable between the 2 postoperative time points (P > .805). At the end of 5 years, 65% of the eyes were within 15 degrees of the preoperative astigmatic meridian. Comparative analysis showed significantly higher surgically induced astigmatism, lower differences in vector and absolute angles of error for the eyes with preoperative with-the-rule (WTR) astigmatism than eyes with against-the-rule (ATR) astigmatism at 5 years (P < .004).
Our study showed the stability of femtosecond (fs)-assisted arcuate keratotomy was well-maintained over 5 years. There was a tendency of increasing overcorrection of preoperative WTR astigmatism and undercorrection of ATR astigmatism over time.
•The effect of corneal astigmatism after femtosecond arcuate keratotomy remained stable over 5 years.•There was a discrepancy in the effect observed for patients with preoperative with-the-rule versus those with against-the-rule corneal astigmatism.•There was a tendency toward increasing overcorrection of preoperative with-the-rule astigmatism and undercorrection of against-the-rule astigmatism over time.
Purpose
Bending Asymmetry Index (BAI) has been proposed to characterize the types of scoliotic curve in three-dimensional ultrasound imaging. Scolioscan has demonstrated its validity and reliability ...in scoliosis assessment with manual assessment-based X-ray imaging. The objective of this study is to investigate the ultrasound-derived BAI method to X-ray imaging of scoliosis, with supplementary information provided for the pre-surgery planning.
Methods
About 30 pre-surgery scoliosis subjects (9 males and 21 females; Cobb: 50.9 ± 19.7°, range 18°–115°) were investigated retrospectively. Each subject underwent three-posture X-ray scanning supine on a plain mattress on the same day. BAI is an indicator to distinguish structural or non-structural curves through the spine flexibility information obtained from lateral bending spinal profiles. BAI was calculated semi-automatically with manual annotation of vertebral centroids and pelvis level inclination adjustment. BAI classification was validated with the scoliotic curve type and traditional Lenke classification using side-bending Cobb angle measurement (S-Cobb).
Results
82 curves from 30 pre-surgery scoliosis patients were included. The correlation coefficient was
R
2
= 0.730 (
p
< 0.05) between BAI and S-Cobb. In terms of scoliotic curve type classification, all curves were correctly classified; out of 30 subjects, 1 case was confirmed as misclassified when applying to Lenke classification earlier, thus has been adjusted.
Conclusion
BAI method has demonstrated its inter-modality versatility in X-ray imaging application. The curve type classification and the pre-surgery Lenke classification both indicated promising performances upon the exploratory dataset. A fully-automated of BAI measurement is surely an interesting direction to continue our endeavor. Deep learning on the vertebral-level segmentation should be involved in further study.
Aim
Colorectal cancer (CRC) is the second commonest cause of cancer death in Taiwan. Although numerous genes have been associated with tumorigenesis in colorectal cancer, only a few have been ...validated and used as biomarkers for predicting clinical outcome. The aim of this study was to analyse the association of APC gene mutation and miR‐21 expression with clinical outcome in CRC patients.
Method
In total, 195 colorectal cancer patients were enrolled in a single medical centre between 2003 and 2007. APC gene mutation and expression of APC and miR‐21 were analysed by direct DNA sequencing and real‐time reverse transcription polymerase chain reaction. The primary outcome included 5‐year overall survival and univariate (Kaplan–Meier) and multivariate (Cox regression) analyses of prognostic factors.
Results
The results showed that 66 (33.8%) of 195 tumour tissues contained an APC mutation. The predominant APC gene variations were deletion mutations (50.0%). APC gene expression was low in CRC and negatively correlated with miR‐21 expression and gene mutation. In advanced‐stage cancer, patients with APC mutation/high miR‐21 had poorer overall survival rates than those with APC mutation/low miR‐21, APC wild‐type/high miR‐21 and APC wild‐type/low miR‐21.
Conclusion
In Taiwan, downregulation of the APC gene in CRC correlated with gene mutation and miR‐21 upregulation. APC mutation and miR‐21 expression could be used to predict the clinical outcome of CRC, especially in patients with advanced disease.
We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese ...population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 α-N-acetyl- neuraminide α-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with P-values of 4.87 × 10(-7) (rs2709736) and 6.05 × 10(-6) (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P=9.74 × 10(-6)) and in CACNB2 (Calcium channel, voltage-dependent, β-2 subunit) gene (rs11013860, P=5.15 × 10(-5)), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P=6.55 × 10(-5) and P=1.48 × 10(-5), respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.
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