Usefulness of aortic valve calcium scores by electron beam computed tomography as a marker for aortic stenosis.
This study was undertaken to determine whether aortic valve calcium (AVC) scores measured by electron beam tomography can identify patients with echocardiographically defined aortic stenosis. Electron beam tomography is increasingly being used to detect coronary artery calcium. AVC can also be measured on electron beam tomographic (EBT) scans obtained to screen for coronary calcium. Whether EBT AVC scores correlate with the presence of aortic stenosis, as assessed by echocardiography, is unknown. Results of this study suggest that AVC scores should be calculated routinely for coronary calcium screening EBT scans, and that patients with Agatston AVC scores above a certain level (e.g., >150) should be referred for echocardiography.


Conformational effects of nucleotide exchange in ras p21 proteins as studied by fluorescence spectroscopy.
The intrinsic fluorescence properties of the oncogene protein p21N-ras,p21H-ras and one of its transforming mutants, p21N-ras (Val12), have been investigated. A mutant containing a single tryptophan at position 28 in p21H-ras (Trp28) has been specifically engineered to provide a probe of protein conformation on nucleotide binding. The proteins produced essentially similar circular dichroism spectra typical of alpha/beta proteins. A decrease in the intensity of the fluorescence emission spectrum due to tyrosine occurred on GDP/GTP nucleotide exchange in the native and mutant proteins. Selective excitation of the single tryptophan in p21 produced a decrease in fluorescence intensity which was accompanied by a blue shift in the wavelength of maximum emission on nucleotide exchange. A reduction in the residual Mg2+ ion concentration enhanced this effect.


Dissecting the genetic architecture of agronomic traits in multiple segregating populations in rapeseed (Brassica napus L.).
Detection of QTL in multiple segregating populations is of high interest as it includes more alleles than mapping in a single biparental population. In addition, such populations are routinely generated in applied plant breeding programs and can thus be used to identify QTL which are of direct relevance for a marker-assisted improvement of elite germplasm. Multiple-line cross QTL mapping and joint linkage association mapping were used for QTL detection. We empirically compared these two different biometrical approaches with regard to QTL detection for important agronomic traits in nine segregating populations of elite rapeseed lines. The plants were intensively phenotyped in multi-location field trials and genotyped with 253 SNP markers. Both approaches detected several additive QTL for diverse traits, including flowering time, plant height, protein content, oil content, glucosinolate content, and grain yield. In addition, we identified one epistatic QTL for flowering time. Consequently, both approaches appear suited for QTL detection in multiple segregating populations.


Streptokinase production from Streptococcus dysgalactiae subsp. equisimilis SK-6 in the presence of surfactants, growth factors and trace elements.
Streptokinase is an extracellular protein secreted by various strains of streptococci and is used clinically as an intravenous thrombolytic agent for the treatment of acute myocardial infarction. It is well established that the fibrinolytic activity of streptokinase originates in its ability to activate plasminogen. The present investigation was carried out to determine the extent of streptokinase production by Streptococcus dysgalactiae subsp. equisimilis SK-6, in the presence of surfactants, growth factors, trace elements and under the influence of different physical parameters. Mineral salt medium was supplemented with different surfactants, growth factors and trace elements. Effects of incubation period and inoculum volume were also studied. Results indicated that the streptokinase yield was higher in the presence of non-ionic surfactants, where Tween 80 supported maximum enzyme production (0.178 U/ml). Growth factors such as glycine and thiamine supplementation resulted in better enzyme production. Trace elements in the form of magnesium sulphate and ferrous sulphate when added in lesser quantity aided higher streptokinase synthesis. Enzyme production was severely affected in the presence of higher concentrations of these inorganic salts. A constant decrease in the enzyme production was observed beyond 48 h of incubation. Among the different inoculum sizes used, 1 % v/v inoculum facilitated highest streptokinase production (0.360 U/ml). The streptokinase production ability of S. dysgalactiae subsp. equisimilis SK-6 offers its potential industrial application for the manufacture of streptokinase.


Low-frequency electromagnetic (eddy-current) holography for imaging in conductors.
Typical eddy-current system test data consist of the values of the system's probe impedance. The wave theory that links the phase response of the eddy-current probe impedance to the defect location relative to the probe is presented. The technique of phase multiplying the diffraction-limited hologram generated from the probe impedance is discussed. The effects and limitations of this technique are illustrated with a mathematical model of the eddy-current probe. Experimental data are presented that confirm the theoretical analysis and illustrate the ability to focus eddy-current holographic data by using backward wave propagation.


Suppression of ponto-geniculo-occipital waves by neurotoxic lesions of pontine caudo-lateral peribrachial cells.
Ponto-geniculo-occipital waves precede rapid eye movement sleep and play an important role in triggering and maintaining rapid eye movement sleep. Ponto-geniculo-occipital waves have been implicated in several important functions such as sensorimotor integration, learning, cognition, development of the visual system, visual hallucination, and startle response. Peribrachial area neurons have long been thought to play a key role in the triggering of ponto-geniculo-occipital wave. However, the exact location within the peribrachial area for triggering pontine ponto-geniculo-occipital wave has not been unequivocally demonstrated. In an attempt to address this issue, kainic acid was microinjected (1.0 micrograms) unilaterally into the caudo-lateral peribrachial area of four cats in order to destroy the cell bodies located in that region and thus to study the effects of their destruction upon waking-sleep states and ponto-geniculo-occipital waves. The kainic acid produced a small spherical area of nerve cell loss and/or gliosis centered on the stereotaxic coordinates of P: 4.0, L: 4.5, and H: -2.5. The maximum diameter of that spherical area of cell loss was 0.9 mm. Unilateral lesioning of the caudo-lateral peribrachial area decreased ponto-geniculo-occipital waves during rapid eye movement sleep by 85% ipsi-laterally and 15% contralaterally in the lateral geniculate body without significantly changing the amounts of time spent in wake, slow-wave sleep, and rapid eye movement sleep. These results suggest that the caudo-lateral peribrachial area cells are critical to the genesis of ponto-geniculo-occipital waves, and provide compelling evidence that the different parts of the peribrachial area have quite different roles in the generation of discrete rapid eye movement sleep signs. We propose that caudo-lateral peribrachial cells exert an excitatory influence on rostral peribrachial cells, which then directly activate the ponto-geniculo-occipital waves that are recorded in the lateral geniculate body. Results of this study are not only important to understand the mechanisms generating ponto-geniculo-occipital waves but also could be used as an experimental tool to study the functions of this wave.


LncRNA DUXAP10 modulates cell proliferation in esophageal squamous cell carcinoma through epigenetically silencing p21.
Esophageal Squamous Cell Carcinoma (ESCC) belongs to malignant tumor of human digestive system. It has greatly threatened human health both mentally and physically. Long non-coding RNAs have been discovered to be special molecular regulators in various cancers, including ESCC. LncRNA DUXAP10 is a newfound RNA, which is able to improve the progression of cancers 1-3 . In this study, DUXAP10 was certified to be upregulated in ESCC tissues and cells. Besides, it was positively correlated with short survival time. Moreover, down-expression of DUXAP10 contributed to decreased cell proliferation and metastasis. Silenced DUXAP10 led to increased apoptosis rate and stagnation of cell cycle. Results of mechanism experiments suggested that DUXAP10 motivated ESCC progression through recruiting enhancer of zeste homolog 2 (EZH2) to the promoter of p21. Our findings suggested that the pseudogene-derived from lncRNA DUXAP10 drove the biological progression of ESCC. DUXAP10 was likely to be a potential therapeutic target for ESCC.


Anti-obesity effects of galacto-oligosaccharides in obese rats.
Galacto-oligosaccharides (GOS) are commonly used as prebiotic with a variety of known metabolic benefits; however, whether GOS plays a protective role in obesity remains unknown. Here, we demonstrate that GOS prevented obesity in a rat model of obesity induced by a high-fat diet. Our results showed that GOS effectively slowed weight gain in diet-induced obese rats without affecting energy intake. GOS significantly suppressed the hypertrophy and hyperplasia of white adipose tissue and markedly reduced the ratio of the fat/body. Consistently, GOS significantly improved serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels, indicating the weight loss activity of GOS. Interestingly, GOS also significantly increased the expression levels of browning proteins, including uncoupling protein 1, peroxisome proliferator-activated receptor-γ, peroxisome proliferator-activated receptor-γ coactivator 1α, and PR domain 16, in both white and brown adipose tissue. Furthermore, we found that GOS markedly increased the expression levels of liver X receptor α, peroxisome proliferation-activated receptor-α, low-density lipoprotein receptor, and cholesterol 7α-hydroxylase proteins in the liver of obese rats. Taken together, we concluded that GOS inhibits obesity by accelerating the browning of white fat cells and the thermogenesis of brown fat cells and that GOS improves host lipid homeostasis by promoting cholesterol catabolism.


The increased risk of multiple sclerosis associated with HLA-DRB1*15:01 and smoking is modified by alcohol consumption.
Previous studies have observed an inverse association between alcohol consumption and multiple sclerosis (MS) risk. We aimed to investigate possible interactions between alcohol consumption, MS-associated human leukocyte antigen (HLA) genes and smoking regarding MS risk. We used a Swedish population-based case-control study (2059 incident cases, 2887 controls) matched by age, sex, and residential area. Subjects with different genotypes and alcohol consumption habits were compared regarding MS risk, by calculating odds ratios with 95% confidence intervals using logistic regression models. Interaction on the additive scale between non-drinking and both genotype and smoking were assessed by calculating the attributable proportion due to interaction (AP). There was a dose-dependent inverse association between alcohol consumption and MS risk (p for trend < 0.0001). A potentiating effect was observed between non-drinking and presence of DRB1*15:01 (AP 0.3, 95% CI 0.2-0.5) which was of similar magnitude irrespective of smoking habits. Non-drinking also interacted with smoking to increase MS risk (AP 0.2, 95% CI 0.06-0.4). Non-drinking interacts with DRB1*15:01 and smoking to increase the risk of MS. Better understanding of the mechanisms behind our findings may help to define ways to achieve protection against MS by other means than alcohol consumption.


Correction to: Providence nighttime bracing is effective in treatment for adolescent idiopathic scoliosis even in curves larger than 35°.
SpineTech should correctly been written as Spinal Technology, inc.


Cloning and expression of 1,2-alpha-mannosidase gene (fmanIB) from filamentous fungus Aspergillus oryzae: in vivo visualization of the FmanIBp-GFP fusion protein.
1,2-alpha-Mannosidase catalyzes the specific cleavage of 1,2-alpha-mannose residues from protein-linked N-glycan. In this study, a novel DNA sequence homologous to the authentic 1,2-alpha-mannosidase was cloned from a cDNA library prepared from solid-state cultured Aspergillus oryzae. The fmanIB cDNA consisted of 1530 nucleotides and encoded a protein of 510 amino acids in which all consensus motifs of the class I alpha-mannosidase were conserved. Expression of the full length of 1,2-alpha-mannosidase cDNA by the Aspergillus host, though it has rarely been done with other filamentous-fungal mannosidase, was successful with fmanIB and caused an increase in both intracellular and extracellular mannosidase activity. The expressed protein (FmanIBp) specifically hydrolyzed 1,2-alpha-mannobiose with maximal activity at a pH of 5.5 and a temperature of 45 degrees C. With Man(9)GlcNAc(2) as the substrate, Man(5)GlcNAc(2) finally accumulated while hydrolysis of the 1,2-alpha-mannose residue of the middle branch was rate-limiting. To examine the intracellular localization of the enzyme, a chimeric protein of FmanIBp with green fluorescent protein was constructed. It showed a dotted fluorescence pattern in the mycelia of Aspergillus, indicative of the localization in intracellular vesicles. Based on these enzymatic and microscopic results, we estimated that FmanIBp is a fungal substitute for the mammalian Golgi 1,2-alpha-mannosidase isozyme IB. This and our previous report on the presence of another ER-type mannosidase in A. oryzae (Yoshida et al., 2000) support the notion that the filamentous fungus has similar steps of N-linked glycochain trimming to those in mammalian cells.


Phosphorylation-dependent interactions of alpha-Actinin-1/IQGAP1 with the AMPA receptor subunit GluR4.
AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors play key roles in excitatory synaptic transmission and synaptic plasticity in the CNS. Although a variety of proteins has been characterized to interact with AMPA receptors and regulate their function, little is known about the regulation of the AMPA receptor subunit GluR4. To understand the molecular mechanisms of GluR4 functional regulation, the yeast two-hybrid system was used to identify GluR4-interacting molecules. alpha-Actinin-1 and IQGAP1 were identified to be GluR4-specific binding partners. Both proteins interact specifically with GluR4 and co-cluster with GluR4 individually in neurons. Mapping experiments revealed that alpha-Actinin-1 and IQGAP1 bind to the same region within the C-terminus of GluR4 that contains a previously identified PKA phosphorylation site, Ser842, phosphorylation of which is regulated by synaptic activity. Interestingly, the phosphorylation of Ser842 differentially regulates interactions of GluR4 with alpha-Actinin-1 and IQGAP1; phosphorylation strongly inhibits interaction of GluR4 with alpha-Actinin-1 but has little effect on its interaction with IQGAP1. These results suggest that alpha-Actinin-1 and IQGAP1 regulate GluR4 functions via their specific associations with GluR4. In addition, our data indicate that activity-dependent phosphorylation of GluR4 may regulate its synaptic targeting through phosphorylation-dependent interactions with alpha-Actinin-1 and IQGAP1.


The physiological role of estradiol 17-sulfate during pregnancy.
To clarify the physiological role of estradiol 17-sulfate (ES) during pregnancy, experiments were conducted and the following results were obtained: (1) serum or urinary ES levels rose as a function of gestational age; (2) placental microsomes showed fairly high 2- and 4-hydroxylase activity for ES; and (3) the catechol products, 2- and 4-hydroxy-ES, had a strong inhibitory effect upon the in vitro production of lipid peroxides. These results suggest that ES acts as a precursor to the catechol metabolites which maintain normal gestation. This is coincident with the negative correlation of serum levels in ES and lipid peroxides observed in late pregnancy.


Dermatology consultations significantly contribute quality to care of hospitalized patients: a prospective study of dermatology inpatient consults at a tertiary care center.
Cutaneous abnormalities are common in hospitalized patients but are frequently missed or misdiagnosed by admitting teams. Inpatient dermatology consultations provide important information to help diagnose and manage these patients. However, few studies have analyzed dermatology inpatient consultations and their effect. We prospectively collected information for 691 consecutive dermatology consultations from November 2013 to November 2014. Patients ranged in age from newborns to 97 years old. The internal medicine service requested the most consultations (45%). Only 6.5% of consultations were requested within 24 hours of appearance of cutaneous findings. Before consultation, 70.3% of patients did not receive treatment for or based on their cutaneous findings. Dermatology consultation resulted in treatment change in 81.9% of patients. The most common diagnoses were drug rash and contact dermatitis. Biopsies confirmed 71.7% of the initial bedside diagnoses by the dermatology consultation team. Common skin diseases were responsible for the majority of dermatology consultations. Most patients were not treated for their cutaneous conditions before the dermatology consultation. Dermatology consultations resulted in treatment changes in the majority of cases.


Peri-articular administration of tranexamic acid is an alternative route in total knee arthroplasty: a systematic review and meta-analysis.
As an antifibrinolytic agent, tranexamic acid (TXA) is increasingly used in total knee arthroplasty (TKA) to reduce blood loss. The administration of intravenous and intra-articular TXA has been well explored, but the most efficient way to administer TXA remains in question. Peri-articular injection (PAI) of TXA is a recently mentioned method. A meta-analysis of the efficacy of PAI TXA in patients after TKA should be performed. A systematic search was performed within PubMed, Embase, and the Cochrane Library up to November 8, 2021. Two authors independently screened studies for eligibility and extracted data for analysis. The primary outcome was haemoglobin change. The secondary outcomes were haematocrit change, total drainage volume, thromboembolic events, and blood transfusion. A total of ten studies were included in this meta-analysis. The results indicated that there was a significant decrease in haemoglobin change when using PAI TXA compared with no TXA (mean difference - 1.05; 95% CI - 1.28 to - 0.81; P < 0.00001; I2 = 0%), but it had no significant differences compared with IA and IV (mean difference - 0.01; 95% CI - 0.17 to - 0.14; P = 0.85; I2 = 39%). There were no significant differences between the TXA < 1.5 g subgroup (0.10, 95% CI - 0.27 to 0.46; P = 0.60; I2 = 0%) and the TXA ≥ 1.5 g subgroup (0.18, 95% CI - 0.12 to 0.48; P = 0.24; I2 = 74%). In addition, the combined group (PAI plus IV or IA) was superior to the IV or IA group in terms of haemoglobin change (mean difference - 0.51; 95% CI - 0.76 to - 0.27; P < 0.0001; I2 = 19%). Regarding haematocrit change, the pooled result showed it was significantly less in the PAI group than the non-TXA group. Similarly, comparing it against the IV subgroup, the result revealed a difference in favour of the PAI group, with a mean difference of - 1.89 g/dL (95% CI - 2.82 to - 0.95; P < 0.0001; I2 = 67%). For total drainage volume, the pooled result was in favour of PAI TXA over no TXA (297 ml, 95% CI - 497.26 to - 97.23; P = 0.004; I2 = 87%), but it had no significant difference compared with IA and IV (mean difference - 37.98; 95% CI - 115.68 to 39.71; P = 0.34; I2 = 95%). There was no significant difference in thromboembolic events (OR 0.74; 95% CI 0.25 to 2.21; P = 0.59; I2 = 0%). Blood transfusion was not significantly different between the PAI group and the non-TXA group (OR 0.50; 95% CI 0.23 to 1.06; P = 0.07; I2 = 21%), and there was no significant difference between PAI and the other two TXA injection methods (OR 0.72; 95% CI 0.41 to 1.25; P = 0.24; I2 = 19%). PAI has comparable effects to IV and IA injections. PAI is an alternative injection route of TXA for patients who have undergone TKA.


The Impact of Centralised Services on Metric Reflecting High-quality Performance: Outcomes from 1110 Consecutive Radical Cystectomies at a Single Centre.
The 2002 National Institute for Health and Care Excellence guidance on centralisation of radical cystectomy (RC) coincided with changes in practice: use of neoadjuvant chemotherapy (NAC) and pelvic lymph node dissection (PLND), and RC for high-risk non-muscle-invasive bladder cancer (HR-NMIBC). To report the outcomes of RC at a single centre and to compare trends in survival with respect to centralisation and change in RC practice. Data were collected retrospectively between 1 January 1994 and 31 December 2016. Patients with urothelial cell carcinoma (UCC) were selected. Outcomes from 1994 to 2007 (before centralisation, era 1) were compared with those from 2008 to 2016 (after centralisation, era 2). The primary outcome was disease-specific mortality. Secondary outcomes were survival and use of NAC and PLND. Overall, 1100 RCs (era 1, 316; era 2, 794) were performed for UCC. Median (interquartile range [IQR]) follow-up was 28.5 (11.9-57.4) mo. RC for NMIBC was 36.2% versus 51.3% (p<0.001), NAC use was 2.2% versus 31.6% (p<0.001), and PLND use was 59.7% versus 76.4% (p<0.001) in era 1 versus era 2. The 30-d (1.6% [era 1] vs 0.8% [era 2], p=0.21) and 90-d (4.1% vs 2.6%, p=0.2) mortality rates did not differ with respect to RC year. Five-year disease-specific survival (DSS) was 56.0% in era 1 versus 79.0% in era 2 (p<0.001). RC for patients aged ≥75 yr was 13.9% versus 28.1% (p<0.001) and 30-d mortality in this group was 4.5% versus 0% (p=0.001) in era 1 versus era 2. The study is limited by its retrospective design. Centralisation was associated with higher rates of NAC and PLND use, and increased RC performed for older patients and patients with HR-NMIBC. DSS was higher and RC appeared to be safer for older patients (fewer postoperative mortalities) after centralisation. We looked at outcomes from bladder removal for bladder cancer. Survival outcomes improved following centralisation of services. Surgery appeared to be safer for older patients, as there were fewer postoperative mortalities after centralisation. Centralisation of radical cystectomy (RC) services was associated with higher rates of neoadjuvant chemotherapy and pelvic lymph node dissection use, and increased usage of RC for older patients with high-risk non-muscle-invasive bladder cancer. Survival outcomes from RC were superior after centralisation and safer for older patients undergoing RC (fewer postoperative mortalities).


Infrainguinal occlusive disease: endovascular intervention is the first line therapy.
The preferred treatment of infrainguinal occlusive disease at many centers has undergone a paradigm shift from open bypass to endovascular intervention as the first-line therapeutic modality. Our own experience supports a percutaneous first approach. Though skeptics initially cited lower primary patency rates for angioplasty when compared with bypass, more recent studies have shown favorable secondary patencies nearly challenging that of bypass. The need for repeat endovascular intervention to achieve a higher secondary patency is not a major deterring factor because most procedures are associated with a short hospital stay and a relatively low rate of complication. The risk is low and this complex group of patients can tolerate minimally invasive reinterventions well. The longevity of this patient population is generally short, and consequently less durable outcomes may be acceptable. Patients do require close follow-up with early treatment of restenosis. However, there appears to be a decreased cost of intervention when compared with surgery. Furthermore, the functional outcomes and quality of life appear more optimal with angioplasty. The concern that angioplasty may preclude future surgical intervention by damaging the distal bypass target has not borne true. It is unusual for a percutaneous therapy to eliminate the possibility of a bypass should the endovascular approach not be successful. Finally, advances in techniques and devices may herald improved outcomes because percutaneous therapy in the periphery is still in the early stages of its maturation. Thus, endovascular intervention has become an established, as well as a developed method for treating peripheral arterial occlusive disease and should be considered the first-line therapeutic modality for patients with.lower extremity vascular disease.


Enhancing functional production of a chaperone-dependent lipase in Escherichia coli using the dual expression cassette plasmid.
The lipase subfamilies I.1 and I.2 show more than 33% homology in the amino acid sequences and most members share another common property that their genes are clustered with the secondary genes whose protein products are required for folding the lipase into an active conformation and secretion into the culture medium. In previous studies, the lipase (LipA) and its chaperone (LipB) from Ralstonia sp. M1 were overexpressed in E. coli and the lipase was successfully refolded in vitro. The purpose of this study was to enhance the production of the active lipase LipA from Ralstonia sp. M1 in the heterologous host E. coli without in vitro refolding process, using two-plasmid co-expression systems and dual expression cassette plasmid systems. To produce more active lipase from Ralstonia sp. M1 in E. coli without in vitro refolding process but with the help of overexpression of the chaperone (LipB1 and LipB3 corresponding to 56-aa truncated and 26-aa truncated chaperone LipB), six different expression systems including 2 two-plasmid co-expression systems (E. coli BL21/pELipABa + pELipB1k and BL21/pELipABa + pELipB3k) and 4 dual expression cassette plasmid systems (BL21/pELipAB-LipB1a, BL21/pELipAB-LipB3a, BL21/pELipA-LipB1a, and BL21/pELipA-LipB3a) were constructed. The two-plasmid co-expression systems (E. coli BL21/pELipABa + pELipB1k and BL21/pELipABa + pELipB3k) produced the active lipase at a level of 4 times as high as the single expression cassette plasmid system E. coli BL21/pELipABa did. For the first time, the dual expression cassette plasmid systems BL21/pELipAB-LipB1a and BL21/pELipAB-LipB3a yielded 29- and 19-fold production of the active lipase in comparison with the single expression cassette plasmid system E. coli BL21/pELipABa, respectively. Although the lipase amount was equally expressed in all these expression systems (40% of total cellular protein) and only a small fraction of the overexpressed lipase was folded in vivo into the functional lipase in soluble form whereas the main fraction was still inactive in the form of inclusion bodies. Another controversial finding was that the dual expression cassette plasmid systems E. coli BL21/pELipAB-LipB1a and E. coli/pELipAB-LipB3a secreted the active lipase into the culture medium of 51 and 29 times as high as the single expression cassette plasmid system E. coli pELipABa did, respectively, which has never been reported before. Another interesting finding was that the lipase form LipA6xHis (mature lipase fused with 6× histidine tag) expressed in the dual expression cassette plasmid systems (BL21/pELipA-LipB1a and BL21/pELipA-LipB3a) showed no lipase activity although the expression level of the lipase and two chaperone forms LipB1 and LipB3 in these systems remained as high as that in E. coli BL21/pELipABa + pELipB1k, BL21/pELipABa + pELipB3k, BL21/pELipAB-LipB1a, and BL21/pELipAB-LipB3a. The addition of Neptune oil or detergents into the LB medium increased the lipase production and secretion by up to 94%. Our findings demonstrated that a dual expression cassette plasmid system E. coli could overproduce and secrete the active chaperone-dependent lipase (subfamilies I.1 and I.2) in vivo and an improved dual expression cassette plasmid system E. coli could be potentially applied for industrial-scale production of subfamily I.1 and I.2 lipases.


Reduction of Tendon Fibrosis Using Galectin-3 Inhibitors.
Fibrosis is a complication of both tendon injuries and repairs. We aim to develop a mouse model to assess tendon fibrosis and to identify an antifibrotic agent capable of overcoming tendon fibrosis. Adult C57Bl/6 mice underwent a skin incision to expose the Achilles tendon, followed by 50% tendon injury and abrasion with sandpaper. Sham surgeries were conducted on contralateral hindlimbs. Histology and immunofluorescent staining for fibrotic markers (Col1, α-SMA) were used to confirm that the model induced tendon fibrosis. A second experiment was conducted to further examine the role of α-SMA in adhesion formation using α-SMA.mTmG mice (6-8 weeks old) (n=3) with the same injury model. The control group (tendon injury) was compared to the sham group, using the contralateral limb with skin incision only. A second experiment was conducted to further examine the role of α-SMA in adhesion formation using α-SMA.mTmG mice (6-8 weeks old) (n=3) with the same injury model. The control group (tendon injury) was compared to the sham group, using the contralateral limb with skin incision only. Lastly, α-SMA.mTmG mice were randomized to either condition 1. Tendon injury (control group) or 2. Tendon injury with Galectin-3 inhibitor (Gal3i) treatment at time of injury (treatment group). Histological analyses confirmed tendon thickening and collagen deposition after tendon injury and abrasion compared to control. Immunofluorescence showed higher levels of Col1 and α-SMA protein expression after injury compared to sham (*p<0.05). RT-qPCR also demonstrated increased gene expression of Col1 and α-SMA after injury compared to sham (*p<0.05). Gal3 protein expression also increased after injury and co-localized with α-SMA positive fibroblasts surrounding the fibrotic tendon. Gal3i treatment decreased collagen deposition and scarring observed in the treatment group (*p<0.05). Flow cytometry analysis further showed reduced numbers of profibrotic fibroblasts (CD26+) in the treatment compared to the control group (*p<0.05). Our study provides a reproducible and reliable model to investigate tendon fibrosis. Findings suggest the potential of Gal3i to overcome fibrosis resulting from tendon injuries.


Toxicity of ochratoxin A in aBrevibacillus brevis - Growth inhibition assay.
Ochratoxin A (OTA) is a nephrotoxic, carcinogenic and immunosuppressive mycotoxin. It can be detoxified by various microorganisms, e.g. different yeast strains, via metabolisation into ochratoxin α (OTα). Within this study a growth inhibition assay was developed to compare the toxicity of OTA and its degradation product OTα. As an indicator organismBrevibacillus brevis was used. The assay was performed in microtiterplates. Growth inhibition was determined by comparing the optical density values ofBrevibacillus brevis cultures grown in medium supplemented with OTA/OTα and OTA/OTα-free medium, respectively.It could be shown thatB. brevis is sensitive to OTA (EC100=0.5 mg/L±0.03 mg/L), which is not the case for its metabolite OTα. Therefore this bioassay is a useful tool to show the detoxification of OTA to OTα by microbial degradation.


Validating Gene Fusion as the Source of Chimeric RNAs.
While chimeric RNAs may be generated by transcription-mediated mechanisms such as "trans-splicing" and "read-through/splicing" (Zhang et al., Cancer Discov 2:598-607, 2012; Zaphiropoulos, Front Genet 2:92, 2011; Li et al., Cell Cycle 8:218-222, 2009; Jividen and Li, Genes Chromosomes Cancer 53:963-971, 2014; Jia et al., Trends Cancer 2:475-484, 2016), most highly expressed chimeric RNA species identified so far are usually transcribed directly from fusion genes. Fusion genes, formed by joining two parental genes as a result of chromosomal rearrangements, are hallmarks of many types of cancer. Various methods can be deployed for confirming a particular fusion gene as the original source of transcribed chimeric RNA. In this chapter, we discuss commonly used methodologies such as genomic DNA breakpoint mapping and fluorescent in situ hybridization useful for confirming gene fusion events. In addition, we highlight the development of new technologies such as de novo whole-genome optical mapping suitable for global analysis of genomic arrangements. The advantages and disadvantages of each of these technologies are presented and compared.


Release of endogenous gamma-aminobutyric acid from vocalization nucleus, the robust nucleus of the archistriatum of zebra finch in vitro.
The release of gamma-aminobutyric acid (GABA) from the robust nucleus of the archistriatum (RA) of the zebra finch was examined in slice preparations. Potassium-induced depolarization caused calcium-dependent release of GABA. GABA release by veratrine was blocked by tetrodotoxin. Electrical stimulation of fibers dorsal to RA also released GABA. There was no sex difference in GABA release per wet weight of RA, while the size of the female RA is smaller than that of the male RA.


Cardiac injury biomarkers in paediatric age: Are we there yet?
The aim of this article is to evaluate the clinical utility of cardiac injury biomarkers in paediatric age. In December 2015, a literature search was performed (PubMed access to MEDLINE citations; http://www.ncbi.nlm.nih.gov/PubMed/ ). The search strategy included the following medical subject headings and text terms for the key words: "cardiac injury biomarkers", "creatine kinase-MB", "myoglobin", "troponin", "children", "neonate/s", "newborn/s", "infant/s" and echocardiography. In the paediatric population, troponins show a good correlation with the extent of myocardial damage following cardiac surgery and cardiotoxic medication and can be used as predictors of subsequent cardiac recovery and mortality. Elevation of cardiac injury biomarkers may also have diagnostic value in cases when cardiac contusion or pericarditis is suspected. Cardiac injury biomarkers are very sensitive markers for the detection of myocardial injury and have been studied in healthy newborns, after tocolysis, intrauterine growth restriction, respiratory distress and asphyxia. The proportion of newborns with elevated troponin was higher than that in ill infants, children, and adolescents and in healthy adults, suggesting that myocardial injury, although clinically occult, is common in this young age group. Results suggest that significant elevation of cord troponin is an excellent early predictor of severity of hypoxic-ischaemic encephalopathy and mortality in term infants. Cardiac biomarkers may also benefit centres without on-site echocardiography with evidence showing good correlation with echo-derived markers of myocardial function. Further studies are needed to better clarify the role of cardiac biomarkers in paediatric age and their correlation with echocardiographic parameters.


Examining the mechanisms by which adverse life events affect having a history of self-harm, and the protective effect of social support.
Psychological models of suicide emphasize perceptions of negative stressors, hopelessness and self-harm as key antecedents to suicidal thoughts/acts. Such models also emphasize the potential protective role of social support in these pathways. However, such pathways have not been tested using population level data. Hence, this study aimed to redress this gap. Questionnaire data regarding 24,444 patient suicide deaths were analysed. All individuals died between 1996 and 2015 and were seen by secondary mental health services in England within 12 months before their death. Mediation analyses, using fitted logistic regression models, investigated direct and indirect pathways between negative stressors, hopelessness and a proxy measure of suicide, namely, self-harm history. In addition, the buffering effects of social support were examined in these pathways. There was a direct effect of negative life events on suicidal behaviors. Supporting contemporary psychological models of suicide, a mediated effect via hopelessness and a protective effect of social support were identified. Social support buffered the pathway between stressful life events and hopelessness, with hopelessness decreasing as social support increased. Causal inferences are inappropriate as the design was cross-sectional. A proxy measure of suicidality was utilized (history of self-harm) as all individuals had died by suicide. This is the first time that population data has been used to test psychological pathways to suicidal acts involving negative stressors, hopelessness and social support. Psychological interventions should focus on increasing social support following negative life events together with ameliorating perceptions of hopelessness.


Real-world in-hospital outcomes and potential predictors of heart failure in primigravid women with heart disease in Southwestern China.
Little is known about the status of maternal, obstetric, and neonatal complications and the potential predictors of developing heart failure (HF) in mothers with underlying heart disease (HD) in Southwestern China. The eligible records from the YiduCloud database from December 1, 2010 to December 31, 2019 were screened. The maternal clinical characteristics and the in-hospital outcomes were collected and compared in primigravid women with and without HD. The HD subtypes analyzed included valvular HD (VHD), cardiomyopathy, adult congenital HD (ACHD), pulmonary hypertension (PH), and other cardiac conditions. Among 45,067 primigravid women, 508 (1.1%) had HD, in which 207 (41%) had ACHD, 66 (13%) had VHD, 84 (17%) had cardiomyopathy, 7 (1%) had PH, and 144 (28%) had other cardiac diseases. The maternal cardiac events and the neonatal complications occurred in 28% and 23.3%, respectively, of women with HD and were predominant in the PH group. In multivariable regression, HF was associated with the New York Heart Association (NYHA) class ≥3 (OR = 15.9, 95% confidence interval [CI] = 2.5-99.7; P = 0.003), heart rate ≥ 100 bpm (OR = 3.8, 95% CI = 1.1-13.5; P = 0.036), ejection fraction ≤60% (OR = 6.4, 95% CI = 2.0-21.0; P = 0.002) and left ventricular end-diastolic diameter ≥ 50 mm (OR = 3.4, 95% CI = 1.1-11.2; P = 0.041) at the beginning of pregnancy. Maternal and neonatal complications are higher in primigravid women with HD particularly in the PH group compared with primigravid women without HD. Women with HD should be guided on the potential predictors for HF and closely monitored during pregnancy to reduce maternal and neonatal complications.


DNA methylation variations at CETP and LPL gene promoter loci: new molecular biomarkers associated with blood lipid profile variability.
Recent findings suggest that DNA methylation, a well-known epigenetic mechanism, is involved in high-density lipoprotein cholesterol (HDL-C) metabolism and increased cardiovascular disease risk. The aim of this study was thus to assess whether DNA methylation within key genes of lipoprotein metabolism is associated with blood lipid profile variability. Ninety-eight untreated familial hypercholesterolaemia patients (61 men and 37 women) were recruited for leucocyte DNA methylation analyses at the LDLR, CETP, LCAT and LPL gene promoter loci using bisulfite pyrosequencing. LPL DNA methylation was correlated with HDL-C (r = 0.22; p = 0.031) and HDL particle size (r = 0.47, p = 0.013). In both sex, CETP DNA methylation was negatively associated with low-density lipoprotein cholesterol levels (r < -0.32; p < 0.05). In men, CETP DNA methylation was associated with HDL-C (r = -0.36; p = 0.006), HDL-triglyceride levels (r = 0.59; p < 0.001) and HDL particle size (r = -0.44, p = 0.019). In visceral adipose tissue from 30 men with severe obesity, the associations between LPL DNA methylation, HDL-C (r = -0.40; p = 0.03) and LPL mRNA levels (r = -0.61, p < 0.001) were confirmed. CETP and LPL DNA methylation levels are associated with blood lipid profile, suggesting that further studies of epipolymorphisms should most certainly contribute to a better understanding of the molecular bases of dyslipidemia.


Long-term outcomes of very-low-birth-weight and low-birth-weight preterm newborns with neonatal seizures: A single-center perspective.
Newborn seizures are frequent in preterm newborns and indicate brain lesions in many cases. The objective of this observational study was to investigate the long-term outcome of very-low-birth-weight (VLBW) and low-birth-weight (LBW) preterm infants with neonatal seizures. We examined 54 preterm infants (40 VLBW and 14 LBW cases) born between 2008 and 2011 with clinical seizures during the neonatal period confirmed by interictal or ictal electroencephalography recordings in a retrospective single-center study. Neurodevelopmental follow-up included an expert neurological examination and cognitive testing (Kaufman Assessment Battery for Children) at a mean age of six years. The (mean ± standard deviation) gestational ages of the VLBW and LBW infants were 27.2 ± 1.9 weeks and 33.4 ± 1.7 weeks, respectively, and the postnatal age at seizure onset was 13 ± 11 days in VLBW infants and 9 ± 8 days in LBW infants, with a wide range of one to 62 days. LBW infants more frequently developed non-motor seizures (50.0%) than VLBW infants did (25.0%), and higher-grade intracranial hemorrhage was the predominant etiology in the VLBW group (18.0%), while the etiology in the LBW group was more heterogeneous and included central nervous system malformations and genetic syndromes. At the mean age of 6.2 ± 2.0, years, 25/54 patients were assessed and 44.4% of the VLBW group and 71.4% of the LBW group showed intellectual impairment. Infantile cerebral palsy was present in 22% of VLBW and 42.9% of LBW infants, respectively. The present analysis of long-term neurodevelopmental outcomes of preterm neonates who experienced seizures shows that the risk for intellectual impairment is not limited only to VLBW infants but may significantly affect LBW infants as well. The etiological spectrum differs in relation to gestational age.


Nitroreduction of 2,4-dinitrotoluene in vitro by cytochrome P-450 induced H4IIE cells.
Conditions have been established for H4IIE rat hepatoma cell cultures in which effects of cytochrome P-450 induction on the metabolism of a munitions wastestream pollutant can be studied. Under these conditions, the polychlorinated hydrocarbon 2,3,4,7,8-pentachlorodibenzfuran (PCDBF) induced cytochrome P-450 (1A1) aryl hydrocarbon hydroxylase (AHH) activity over a wide range of concentrations without significant cytotoxic effects. The munition pollutant 2,4-dinitrotoluene (2,4-DNT) did not induce AHH activity itself, but its metabolism was considerably altered when applied to PCDBF induced cultures. Production of amino nitrotoluene isomers was greatly enhanced in induced cultures as compared to uninduced controls, as was the conversion of radiolabeled 2,4-DNT to relatively more polar metabolites. To some extent, the results with H4IIE cells parallel those reported for animals exposed to 2,4-DNT after induction of cytochrome P-450 AHH activity. The preliminary findings suggest that with further development and validation, H4IIE cultures could be of use in characterizing metabolites that result from exposure to chemical mixtures involving a P-450 (1A1) inducer.


Involvement of vanilloid receptors in heat stress-induced delayed protection against myocardial ischemia-reperfusion injury.
Sprague-Dawley rats were pretreated with whole body hyperthermia (rectal 42 degrees C) for 15 min, 24 h before the experiments, and then the left main coronary artery of rat hearts was subjected to a 60 min occlusion followed by 3 h reperfusion. Myocardium injury degree was evaluated by measurement of infarct size and serum creatine kinase (CK) activity. Plasma concentrations of calcitonin gene-related peptide (CGRP), and the expression of alpha- and beta-CGRP mRNA in dorsal root ganglia were determined by radioimmunoassay and semi-quantitative reverse-transcription polymerase chain reaction, respectively. Hyperthermia treatment significantly reduced infarct size and CK release concomitantly with a dramatic increase in plasma concentrations of CGRP and the expression of alpha-CGRP mRNA, but not beta-CGRP mRNA, which was completely abolished by pretreatment with capsazepine (38 mg/kg, s.c.), a competitive vanilloid receptor 1 antagonist. These results suggests that vanilloid receptor 1 on capsaicin-sensitive sensory nerves plays an important role in the modulation of the delayed cardioprotection induced by heat stress in rats.


A phase I study of pyrazofurin.
Sixty-one patients with advanced disseminated cancer were given progressively increasing doses of pyrazofurin to evaluate toxicity patterns and to establish the dosage that produces maximum therapeutic effect with clinically tolerable toxicity. The drug was given by intravenous injection over 5-day courses repeated every 2--3 weeks. Toxic reactions included stomatitis, myelosuppression, skin rash, erythema, proctitis, and occasional nausea and vomiting. Stomatitis was the dose-limiting toxicity and it occurred in 32 patients. Myelosuppression was mild to moderate. Of 75 evaluable courses for marrow toxicity, leukopenia occurred in 14 and thrombocytopenia in 28. Thrombocytopenia was apparently dose-independet. Marrow recovery was complete by day 21 of therapy. Twelve patients developed mild or severe cutaneous toxicity depending on dose. When mild, the skin changes consisted of self-limited erythema or rash, and when severe, bullous lesions and skin ulcers were also observed. Proctitis occurred in six patients and was associated with severe stomatitis. Nausea and vomiting were occasional and mild. There was no evidence of liver or renal toxicity. All toxic manifestations other than marrow toxicity were dose-related. No responses were observed. A reasonable dose schedule is 45 mg/m2/day X 5 repeated every 3 weeks. We recommend that Phase II studies be pursued particularly in diseases that have been shown to be sensitive to the drug.


In vitro antibacterial activity of SK&F 88070 against aerobic gram-positive and gram-negative cocci and Haemophilus influenzae.
The inhibitory activity of SK&F 88070, a cephalosporin whose kinetic characteristics in animals suggest the possibility of once-daily doses, was determined against 345 clinical isolates, and results were compared with the activities of ceftizoxime, ceftriaxone, moxalactam, methicillin, and ampicillin. The spectrum of SK&F 88070 is similar to that of ceftizoxime.


Amblyopic children read more slowly than controls under natural, binocular reading conditions.
Recent evidence suggests that amblyopia results in fixation instability and atypical saccades. Reading is a vision-reliant ability that requires sequential eye movements, including forward and regressive saccades. This study investigated reading and associated eye movements in school-age amblyopic children. Amblyopic children with strabismus and/or anisometropia (n = 29) were compared to nonamblyopic children treated for strabismus (n = 23) and normal control children (n = 21). While fitted with the ReadAlyzer, an eye movement recording system, children silently read a grade-level paragraph of text during binocular viewing. Reading rate, number of forward and regressive saccades per 100 words, and fixation duration were determined. Comprehension was evaluated with a 10-item quiz; only data from children with at least 80% correct responses were included. Amblyopic children read more slowly and had more saccades compared with nonamblyopic children with treated strabismus and normal controls. Fixation duration did not differ significantly for amblyopic children versus normal controls. Treated strabismic children without amblyopia did not differ significantly from normal controls on any reading measure. Amblyopic eye visual acuity was not correlated with any reading measure. Amblyopia was associated with slower reading speed in school-age children. Treatment for monocular amblyopia visual acuity impairment could improve reading speed and efficiency.


Insecticide exposure and farm history in relation to risk of lymphomas and leukemias in the Women's Health Initiative observational study cohort.
Relationships of farm history and insecticide exposure at home or work with lymphohematopoietic (LH) neoplasm risk were investigated in a large prospective cohort of US women. In questionnaires, women self-reported history living or working on a farm, personally mixing or applying insecticides, insecticide application in the home or workplace by a commercial service, and treating pets with insecticides. Relationships with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, plasma cell neoplasms, and myeloid leukemia were investigated using Cox proportional hazard models. Age and farming history were explored as effect modifiers. The analysis included 76,493 women and 822 NHL cases. Women who ever lived or worked on a farm had 1.12 times the risk of NHL (95% confidence interval [CI] = 0.95-1.32) compared to those who did not. Women who reported that a commercial service ever applied insecticides in their immediate surroundings had 65% higher risk of CLL/SLL (95% CI = 1.15-2.38). Women aged less than 65 years who ever applied insecticides had 87% higher risk of DLBCL (95% CI = 1.13-3.09). Insecticide exposures may contribute to risk of CLL/SLL and DLBCL. Future studies should examine relationships of LH subtypes with specific types of household insecticides.


Pulmonary Manifestations of Congenital Heart Disease in Children.
This review addresses how anomalous cardiovascular anatomy imparts consequences to the airway, respiratory system mechanics, pulmonary vascular system, and lymphatic system. Abnormal formation or enlargement of great vessels can compress airways and cause large and small airway obstructions. Alterations in pulmonary blood flow associated with congenital heart disease (CHD) can cause abnormalities in pulmonary mechanics and limitation of exercise. CHD can lead to pulmonary arterial hypertension. Lymphatic abnormalities associated with CHD can cause pulmonary edema, chylothorax, or plastic bronchitis. Understanding how the cardiovascular system has an impact on pulmonary growth and function can help determine options and timing of intervention.


Antioxidant capacity contributes to protection of ketone bodies against oxidative damage induced during hypoglycemic conditions.
Ketone bodies play a key role in mammalian energy metabolism during the suckling period. Normally ketone bodies' blood concentration during adulthood is very low, although it can rise during starvation, an exogenous infusion or a ketogenic diet. Whenever ketone bodies' levels increase, their oxidation in the brain rises. For this reason they have been used as protective molecules against refractory epilepsy and in experimental models of ischemia and excitotoxicity. The mechanisms underlying the protective effect of these compounds are not completely understood. Here, we studied a possible antioxidant capacity of ketone bodies and whether it contributes to the protection against oxidative damage induced during hypoglycemia. We report for the first time the scavenging capacity of the ketone bodies, acetoacetate (AcAc) and both the physiological and non-physiological isomers of beta-hydroxybutyrate (D- and L-BHB, respectively), for diverse reactive oxygen species (ROS). Hydroxyl radicals (.OH) were effectively scavenged by D- and L-BHB. In addition, the three ketone bodies were able to reduce cell death and ROS production induced by the glycolysis inhibitor, iodoacetate (IOA), while only D-BHB and AcAc prevented neuronal ATP decline. Finally, in an in vivo model of insulin-induced hypoglycemia, the administration of D- or L-BHB, but not of AcAc, was able to prevent the hypoglycemia-induced increase in lipid peroxidation in the rat hippocampus. Our data suggest that the antioxidant capacity contributes to protection of ketone bodies against oxidative damage in in vitro and in vivo models associated with free radical production and energy impairment.


An Allelic Variant of the Broad-Spectrum Blast Resistance Gene Ptr in Weedy Rice Is Associated with Resistance to the Most Virulent Blast Race IB-33.
Rice resistance (R) genes have been effectively deployed to prevent blast disease caused by the fungal pathogen Magnaporthe oryzae, one of the most serious threats for stable rice production worldwide. Weedy rice competing with cultivated rice may carry novel or lost R genes. The quantitative trait locus qBR12.3b was previously mapped between two single nucleotide polymorphism markers at the 10,633,942-bp and 10,820,033-bp genomic positions in a black-hull-awned (BHA) weed strain using a weed-crop-mapping population under greenhouse conditions. In this study, we found a portion of the known resistance gene Ptr encoding a protein with four armadillo repeats and confers a broad spectrum of blast resistance. We then analyzed the sequences of the Ptr gene from weedy rice, PtrBHA, and identified a unique amino acid glutamine at protein position 874. Minor changes of protein conformation of the PtrBHA gene were predicted through structural analysis of PtrBHA, suggesting that the product of PtrBHA is involved in disease resistance. A gene-specific codominant marker HJ17-13 from PtrBHA was then developed to distinguish alleles in weeds and crops. The PtrBHA gene existed in 207 individuals of the same mapping population, where qBR12.3b was mapped using this gene-specific marker. Disease reactions of 207 individuals and their parents to IB-33 were evaluated. The resistant individuals had PtrBHA whereas the susceptible individuals did not, suggesting that HJ17-13 is reliable to predict qBR12.3b. Taken together, this newly developed marker, and weedy rice genotypes carrying qBR12.3b, are useful for blast improvement using marker assisted selection.


Offspring birth weight, gestational age and maternal characteristics in relation to glucose status at age 53 years: evidence from a national birth cohort.
We investigated pathways linking offspring birth weight to maternal diabetes risk in later life by taking into account a range of prospective early-life and adult maternal factors. In a national birth cohort study, we examined the relationship between offspring birth weight and maternal glycated haemoglobin (HbA1c) at age 53 years in 581 mothers who had a first birth between age 19 and 25 years, and had data on potential confounders or mediators. Mean age at first birth was 21.5 years. After adjustment for maternal body mass index (BMI), mean percentage change in maternal HbA1c per kilogram increase in offspring birth weight was -1.8%[95% confidence interval (CI) -3.5, -0.1; P = 0.03]. This relationship was mostly accounted for by gestational age that was inversely related to maternal HbA1c (-0.9%; 95% CI -1.5, -0.4; P = 0.001). Other risk factors for high HbA1c were smoking and high BMI at 53 years. There was a significant interaction between offspring birth weight and maternal childhood social class (P = 0.01). Mothers from a manual background with higher birth weight offspring had lower HbA1c (BMI adjusted: -3.1%; 95% CI -5.0, -1.1); this was not observed for mothers from a non-manual background (BMI adjusted: 1.9%; 95% CI -1.3, 5.0). Short gestational age and low offspring birth weight may be part of a pathway linking impaired early maternal growth to diabetes risk in later life. A second possible pathway linking higher offspring birth weight to later maternal glucose status was also identified. These potential pathways require further investigation in cohorts with a wider maternal age range so that the early targeting of public health initiatives can be assessed.


The permeability of 51Cr between cerebrospinal fluid and internal ear.
Radioactively labelled chromium was instilled in the cerebrospinal fluid of guinea pigs. After different intervals, the radioactivity of inner ear fluids was measured and compared with those of other regions. The results lead to kinetic information about the permeability of 51Cr between cerebrospinal and inner ear fluids.


Forest understory plant and soil microbial response to an experimentally induced drought and heat-pulse event: the importance of maintaining the continuum.
Drought duration and intensity are expected to increase with global climate change. How changes in water availability and temperature affect the combined plant-soil-microorganism response remains uncertain. We excavated soil monoliths from a beech (Fagus sylvatica L.) forest, thus keeping the understory plant-microbe communities intact, imposed an extreme climate event, consisting of drought and/or a single heat-pulse event, and followed microbial community dynamics over a time period of 28 days. During the treatment, we labeled the canopy with (13) CO2 with the goal of (i) determining the strength of plant-microbe carbon linkages under control, drought, heat and heat-drought treatments and (ii) characterizing microbial groups that are tightly linked to the plant-soil carbon continuum based on (13) C-labeled PLFAs. Additionally, we used 16S rRNA sequencing of bacteria from the Ah horizon to determine the short-term changes in the active microbial community. The treatments did not sever within-plant transport over the experiment, and carbon sinks belowground were still active. Based on the relative distribution of labeled carbon to roots and microbial PLFAs, we determined that soil microbes appear to have a stronger carbon sink strength during environmental stress. High-throughput sequencing of the 16S rRNA revealed multiple trajectories in microbial community shifts within the different treatments. Heat in combination with drought had a clear negative effect on microbial diversity and resulted in a distinct shift in the microbial community structure that also corresponded to the lowest level of label found in the PLFAs. Hence, the strongest changes in microbial abundances occurred in the heat-drought treatment where plants were most severely affected. Our study suggests that many of the shifts in the microbial communities that we might expect from extreme environmental stress will result from the plant-soil-microbial dynamics rather than from direct effects of drought and heat on soil microbes alone.


Technical description of a novel device for external ventricular drainage in neonatal and pediatric patients: Results from a single referral center experience.
Since external ventricular drainage (EVD) related infections are usually due to skin flora, an extradural intra/extra-cranial accessory device, developed for pediatric patients under three years of age undergoing EVD positioning, is described. The aim of this paper is to provide technical description of this device, underlining the possibility to reduce infective risk and to prevent EVD dislocation. Patients undergoing A-D device EVD placement between 1990 and 2017 at authors' institution were retrospectively considered. The device was made of a fully MRI-compatible inert material (Ketron-Peek-1000), composed of two pieces securely fixable to the skull, bridging the catheter directly from the epidural space to the extracranial space without letting it come in contact with the skin. A total number of 350 patients were considered. The mean age was 1.4 years, being the youngest patient a newborn of 25 weeks of gestational age. Mean time of EVD maintenance was 45 days, ranging from 21 to 81 days. 2 cases (0.6%) of EVD related infections were reported, while, pull-out of the ventricular catheter occurred in 3 cases (0.9%). No cases of bone fractures related to the clamp effect provided by A-D device were reported in the series CONCLUSIONS: This device could represent a safe and feasible option to reduce EVD related infections and catheter pull-out in pediatric patients. The encouraging results could strength the aim of the device to allow safer and longer length of CSF drainage. Moreover, the fully MRI-compatible nature and its non-magnetic properties allow to use it with neuronavigation systems.


Modification of the Catalytic Properties of Erythrocyte Aldehyde Dehydrogenase in Rats after Nitric Oxide Inhalation.
We studied aldehyde dehydrogenase activity in erythrocytes from healthy rats and animals with thermal trauma after NO inhalation. NO had an activating effect on catalytic properties of aldehyde dehydrogenase in healthy rats and burned animals. The effect of NO was more pronounced during burn disease.


The factor structure of a short acculturation scale for Filipino Americans in an adult U.S.-born sample.
The influx of non-European immigrants since 1965 ushered the development and use of acculturation measures in immigrant health studies. A Short Acculturation Scale for Filipino Americans (ASASFA) represents a validated, unidirectional ethnic-specific measure used with first-generation FAs. ASASFA's psychometric properties with adult U.S.-born children-the second generation-remain unexplored. This study determined (a) the factor structure of ASASFA with adult U.S.-born FAs and (b) the predictors of their acculturation scores. A secondary analysis was conducted on ASASFA data from a mental health survey of 116 U.S.-born FAs. Exploratory factor and parallel analyses showed a two-factor solution: language use and preference (Factor 1) and ethnic social relations (Factor 2). Ordinary least squares regression indicated gender and ethnic self-identification predict Factor 1 scores; self-identification solely predicts Factor 2 scores. Results demonstrate ASASFA's validity and parsimony, supporting its use in FA health studies when lengthy bidirectional acculturation measures become impractical.


Effects of culture conditions on susceptibility of alveolar epithelial cell monolayers to NO2.
The effects of nitrogen dioxide (NO2) exposure on primary cultured monolayers of rat type II pneumocytes were investigated as a function of the isolation and culture conditions. Monolayers were cultured in Eagle's minimum essential medium (MEM) and in MEM supplemented with Ham's F-12; in some experiments, the initial cell suspension was also replated after 3 h. Both supplementation of the basal medium and replating increased the sensitivity of the monolayers to NO2, as measured by reduction in dome formation of plastic dishes 24 h post-exposure. These findings suggest that comparisons of in vitro toxicologic observations may be complicated by the effects of specific experimental conditions.


Quantitation of DNA sequences in environmental PCR products by a multiplexed, bead-based method.
A first application of a multiplexed, bead-based method is described for determining the abundances of target sequences in an environmental PCR product. Target sequences as little as 0.3% of the total amount of DNA can be quantified. Tests were conducted on 16S ribosomal DNA sequences from microorganisms collected from contaminated groundwater.


The mitochondrial genome of Protohermes concolorus Yang et Yang 1988 (Insecta: Megaloptera: Corydalidae).
The first complete mitochondrial genome of dobsonfly Protohermes concolorus Yang et Yang, 1988 (Megaloptera: Corydalidae) was sequenced in this study. The genome was a circular molecule of 15,851 bp containing the typical 37 genes that arranged in the same order as that of the putative ancestor of hexapods. Sequences overlaps were observed between several neighbor genes, which made the genome relatively compact. The tRNA-Ser (GCT) could not be folded into typical secondary structure because its DHU arm was replaced with a simple loop. Six of the 13 protein genes were terminated with a single T adjacent to a downstream tRNA gene in the same strand. The variation of GC content caused the different nucleotide substitution patterns of the protein genes. The genome was AT-biased with a total A + T content of 75.83% which was also demonstrated by the codon usage. The control region was the most AT-rich region with a sub-region of even higher A + T content. Protein genes of two strands presented opposite CG-skew trends which was also reflected by the codon usage. For most of the amino acids, the protein coding sequences did not prefer to use the cognate codons of corresponding tRNAs and the codon usage of the protein genes was not random. The variation of nucleotide substitution patterns of protein genes was significantly correlated with the GC content. The phylogenetic analyses based on all the 13 protein genes showed that Megaloptera was the sister group of other holometabolous insects except Coleoptera.


Higher education non-completion, employers, and labor market integration: Experimental evidence.
Theories of job assignment suggest that employers give a lot of weight to achieved educational credentials. But what if credentials are missing? We theorize how college non-completion affects the hiring chances, identify its causal effect in different labor market segments, and assess which factors facilitate labor market entry for dropouts. Based on a simulated hiring process with N = 1382 German employers who rated more than 10,000 fictitious CVs, we show that college non-completion is not a scar per se, but rather depends on the educational attainment of the competitors who constitute the labor queue, and on the degree of occupational closure which varies on a granular level between firms that hire for the same occupations. We also find that employers, when rating dropouts, attach most value to CV attributes that signal a high stock of job-relevant skills, such as good performance during college or an occupation-specific internship. We conclude by discussing implications of our work for research on the labor market integration of dropouts.


Interaction between ionizing radiation and estrogen: what we are missing?
Following complexity as a new approach in science of 21st century biomonitoring of biological effects caused by ionizing radiation received an option of a new dimension. Insight in biological response of mammals to ionizing radiation exposure by integration of genome, non-genome and distant organ bystander effects will significantly change evaluation of health risk and preventive measures. Impact of estrogen on carcinogenesis caused by occupational or accidental exposure to ionizing radiation additionally enables biodosimetry to recognize vulnerable subpopulations according to gender and age. Estrogen, as a potent molecule involved in number of biological pathways during development and adulthood, shows close interaction with pathological processes launched by overexposure to ionizing radiation which should be included in future research and radiation protection.


Beating heart coronary artery bypass surgery after orthotopic heart transplantation.
Beating-heart coronary artery bypass surgery was performed in a 52-year-old man with accelerated transplant coronary artery disease 10 years after orthotopic heart transplantation. Transplant coronary artery disease was first detected in the left circumflex coronary artery 9 years after transplantation. Rapid progression to triple vessel disease occurred within 1 year, and the patient developed worsening symptoms of shortness of breath and chest pain. He underwent off-pump "beating heart" left internal mammary artery to left anterior descending coronary artery bypass surgery. The circumflex coronary artery was not graftable due to diffuse and truncated small vessel disease. His postoperative course was uneventful and he was discharged on the fifth postoperative day. Coronary angiography 3 months after the surgery revealed a widely patent left internal mammary artery to left anterior descending artery bypass. He is alive and symptom free more than 1 year after his surgery.


Identification of the onchocerciasis vector in the Kakoi-Koda focus of the Democratic Republic of Congo.
The objective of this study was to characterise the vector in a small hyper-endemic focus of onchocerciasis (the Kakoi-Koda focus) which has recently been discovered on the western slopes of the rift valley above Lake Albert. Aquatic stages of blackflies were collected by hand from streams and rivers, and anthropophilic adult females were collected by human landing catches. Using a combination of morphotaxonomy and DNA barcoding, the blackflies collected biting humans within the focus were identified as Simulium dentulosum and Simulium vorax, which were also found breeding in local streams and rivers. Simulium damnosum s.l., Simulium neavei and Simulium albivirgulatum were not found (except for a single site in 2009 where crabs were carrying S. neavei). Anthropophilic specimens from the focus were screened for Onchocerca DNA using discriminant qualitative real-time triplex PCR. One specimen of S. vorax was positive for Onchocerca volvulus in the body, and out of 155 S. dentulosum, 30% and 11% were infected and infective (respectively). Simulium dentulosum currently appears to be the main vector of human onchocerciasis within the Kakoi-Koda focus, and S. vorax may be a secondary vector. It remains possible that S. neavei was the main (or only) vector in the past having now become rare as a result of the removal of tree-cover and land-use changes. Simulium vorax has previously been shown to support the development of O. volvulus in the laboratory, but this is the first time that S. dentulosum has been implicated as a probable vector of onchocerciasis, and this raises the possibility that other blackfly species which are not generally considered to be anthropophilic vectors might become vectors under suitable conditions. Because S. dentulosum is not a vector in endemic areas surrounding the Kakoi-Koda focus, it is probable that the Kakoi-Koda focus is significantly isolated.


Disease progression in cardiac transthyretin amyloidosis is indicated by serial calculation of National Amyloidosis Centre transthyretin amyloidosis stage.
Cardiac transthyretin amyloidosis (ATTR-CM) is a progressive and fatal condition. Prognosis can be determined at diagnosis according to the National Amyloidosis Centre (NAC) transthyretin amyloidosis (ATTR) stage. We sought to examine how NAC ATTR stage changes during follow-up and whether it maintains its prognostic value throughout the disease course. We performed a retrospective study of 945 patients with wild-type ATTR-CM (wtATTR-CM) or hereditary ATTR-CM associated with the V122I variant (V122I-hATTR-CM) who were diagnosed and serially evaluated at the UK NAC. Patients who commenced any disease-modifying therapy for amyloidosis were censored at the time of doing so. Landmark Kaplan-Meier survival analyses were performed at diagnosis (n = 945) and at 6 ± 1 (n = 432), 12 ± 3 (n = 562), and 24 ± 3 (n = 316) months and stratified by recalculated NAC ATTR stage at the relevant time point. Cox regression analyses were performed to assess the prognostic significance during follow-up of an increase in NAC ATTR stage from Stage I at diagnosis. Mortality in ATTR-CM was predicted by NAC ATTR stage at each time point [Stage II vs. I, hazard ratios (HRs) 1.95-2.67; P < 0.001; Stage III vs. II, HRs 1.64-2.25; P < 0.001-0.013]. An increase from NAC ATTR Stage I, which occurred in 21%, 32%, and 44% of evaluable patients at 6, 12, and 24 months of follow-up respectively, was highly predictive of ongoing mortality at each time point (HRs 2.58-3.22; P < 0.001) and in each genotypic subgroup (HRs 1.86-4.38; P < 0.05). Increase in NAC ATTR stage occurred earlier in V122I-hATTR-CM than in wtATTR-CM (43% vs. 27% at 12 months of follow-up; P = 0.003). National Amyloidosis Centre ATTR stage predicts ongoing survival throughout the disease natural history in ATTR-CM, and an increase from NAC ATTR Stage I at diagnosis to a higher NAC ATTR stage predicts mortality throughout follow-up. Serial calculation of NAC ATTR stage suggests a more aggressive phenotype in V122I-hATTR-CM than in wtATTR-CM.


Video-assisted removal of a ventricular mass through the mitral valve.
We report the case of 31-year-old man who was admitted for cerebellar ischemia. The echocardiography showed an intraventricular mass, mobile with the cardiac activity compatible with a thrombus or a myxoma. He successfully underwent a video-assisted removal of the mass, through the mitral valve.


Delivering best care and maintaining emotional wellbeing in the intensive care unit: the perspective of experienced nurses.
This study explored the perspective of experienced intensive care nurses regarding maintenance of their emotional wellbeing. Caring for critically ill patients has been identified as stressful. The demand for critical care nurses continues to grow in a climate of an ongoing nursing shortage and an aging workforce. This study sought to understand what environmental elements optimized the maintenance of emotional wellbeing. Grounded theory. Fifteen experienced intensive care unit registered nurses from a metropolitan hospital in Western Australia, were interviewed. Five categories were identified: 'achieving best care', 'caring for the patient's family', 'autonomy within the ICU environment', 'teamwork', and 'previous nursing and life experience'. The findings from this study increase our understanding of the environmental elements that can optimize the emotional wellbeing of intensive care nurses. These findings will assist in the development of strategies to retain nurses in the ICU area.


Evolution and current state of Advance Care Planning in Canada.
Canada is one of the early pioneers of Advance Care Planning concepts, processes, programs and initiatives. The evolution of national messages, models and frameworks is shaped by our publicly funded healthcare system and culturally diverse populations. Our Pan-Canadian Community Framework highlights the importance of individuals, those that matter to them, communities, organizations, and healthcare professionals collaborating, integrating, sharing, and building upon each other's strengths and successes. This framework describes Canada's priority actions at national, provincial and local levels. Our collective vision is for Advance Care Planning to be a part of the life journey.


Acetylation of amino groups and its effect on the conformation and immunological activity of obalbumin.
A procedure is described for the specific acetylation of the lysine residues of ovalbumin. Six acetylated ovalbumins varying in the degree of modification from 21 to 98% were prepared and were found to be homogeneous by polyacrylamide gel electrophoresis, immunodiffusion, and immunoelectrophresis. As expected, the anodic movement of ovalbumin increased and the isoionic point shifted to lower pH values with progressive acetylation of the protein. Measurements on ultraviolet absorption, fluorescence, tryptic digestion, intrinsic viscosity, gel filtration behavior, and immunological reactivity demonstrated that the native folded conformation of ovalbumin was appreciably altered by acetylation. However, even the maximally modified ovalbumin retained considerable residual structure consisting of regions of ordered structure containing antigenic determinants.


Protocol biopsy-driven interventions after pediatric renal transplantation.
The therapeutic value of protocol biopsies (PBs) in renal transplant recipients remains unclear. We performed protocol biopsies in 57 children six months after transplantation. We increased the CNI dose in patients with borderline findings. In cases of Banff grade Ia, six prednisolone IV-pulses were given and the CNI dose was increased. CNI toxicity and polyomavirus nephropathy led to a reduction in the CNI dose. GFR was compared with a control group of 51 children with no PBs transplanted in the same period. Forty-two percent of PBs had no pathological changes, 24% IF/TA. Borderline findings were detected in 11%, Banff grade Ia in 15% (CNI), toxicity in 8%, and one case showed polyomavirus nephropathy. GFR after 1.5 and 2.5 yr was similar in both groups. GFR 3.5 yr after transplantation was significantly higher in the intervention group (57 ± 17 vs. 46 ± 20). Patients treated with low-dose CNI and everolimus had a significantly lower number of pathological findings in PBs. The performance of protocol biopsies followed by a standardized treatment algorithm led to better graft function 3.5 yr after transplantation. Prospective randomized studies to confirm our findings are needed.


Temporomandibular joint axiography and MRI findings: a comparative study.
Axiography may be useful in the evaluation of condyle motion and the effects of internal derangements on this motion. Fifty-one patients were selected by one investigator (RHT) to provide a representative sample of asymptomatic and symptomatic subjects for the following categories: (1) normal disk position, (2) disk displacement with reduction, (3) disk displacement without reduction and (4) disk displacement without reduction associated with degenerative joint disease. Axiography was performed by a separate investigator (KGP) in a blinded fashion. The diagnosis of the presence of internal derangement was based on the tracings only. All subjects had bilateral magnetic resonance imaging scans to evaluate for the presence or absence of internal derangement. The diagnostic sensitivity was 0.64, which indicated that axiography is marginal at identifying disease when present. The negative predictive value was 0.78, which indicated that axiography is accurate in the detection of normal disk condyle relationship.


Steam pops during irrigated radiofrequency ablation: feasibility of impedance monitoring for prevention.
Steam pops are a risk of irrigated radiofrequency catheter ablation (RFA) and may cause cardiac perforation. Data to guide radiofrequency (RF) energy titration to avoid steam pops are limited. This study sought to assess the frequency and consequence of audible pops and to determine the feasibility of using the magnitude of impedance change to predict pops. We reviewed consecutive endocardial open-irrigated RFA for ventricular tachycardia (VT) with continuously recorded ablation data in 142 patients with structural heart disease. Steam pops were defined as an audible pop associated with a sudden spike in impedance. Ablation lesions before or after pops served as controls. From a total of 4,107 ablation lesions, 62 (1.5%) steam pops occurred in 42 procedures in 38 patients. Perforation with tamponade occurred with 1 of 62 (2%) pops. Applications with pops had a greater impedance decrease (22 +/- 7 Omega vs. 18 +/- 8 Omega, P = .001) and a higher maximum power (45 +/- 5 W vs. 43 +/- 6 W, P = .011), but did not differ in maximum catheter tip temperature (40 degrees C +/- 4 degrees C vs. 40 degrees C +/- 4 degrees C, P = .180) from applications without pops. Eighty percent of pops occurred after impedance decreased by at least 18 Omega. During VT ablation with open irrigation, audible pops are infrequent and do not usually cause perforation. Limiting RF power to achieve an impedance decrease of <18 Omega is a feasible method of reducing the likelihood of a pop when perforation risk is of concern.


Purification of snRNPs U1, U2, U4, U5 and U6 with 2,2,7-trimethylguanosine-specific antibody and definition of their constituent proteins reacting with anti-Sm and anti-(U1)RNP antisera.
Small nuclear ribonucleoprotein particles (snRNPs) of the U-snRNP class from Ehrlich ascites tumor cells were purified in a one-step procedure by affinity chromatography with antibodies specific for 2,2,7-trimethylguanosine (m23.2.7G), which is part of the 5'-terminal cap structure of snRNAs U1-U5. Antibody-bound snRNPs are desorbed from the affinity column by elution with excess nucleoside m23.2.7G; this guarantees maintenance of their native structure. The snRNPs U1, U2, U4, U5 and U6 can be recovered quantitatively from nuclear extracts by this procedure. Co-isolation of U6 snRNP must be due to interactions between this and other snRNPs, as anti-m23.2.7G antibodies do not react with deproteinized U6 snRNA. We have so far defined nine proteins of approximate mol. wts. 10 000, 12 000, 13 000, 16 000, 21 000, 28 000, 32 000, 34 000 and 75 000. Purified snRNPs react with anti-(U1)RNP and with anti-Sm antisera from patients with mixed connective tissue disease and from MRL/l mice. As determined by the protein blotting technique, six of the snRNP polypeptides, characterized by apparent mol. wts. 13 000, 16 000, 21 000, 28 000, 34 000 and 75 000, bear antigenic determinants for one or the other of the above autoantibody classes. This suggests strongly that the U-snRNPs produced by the procedure described here are indeed representative of the snRNPs in the cell. With highly purified snRNPs available, investigation of possible enzymic functions of the particles may now be undertaken.


Synthesis of protected guanidinium linked dinucleoside incorporable into an oligonucleotide using solid phase DNA methodology.
The synthesis of novel fully protected guanidinium linked dinucleoside for incorporation into oligonucleotide using solid-phase DNA synthesis methodology was developed. The three different protecting groups selected allow different deprotection conditions.


Individualisation of oral anticoagulant therapy.
The hepatic synthesis of vitamin K dependent coagulation factors is modified by oral anticoagulant drugs, resulting in the release of functionally deficient coagulation factors into the circulation and consequently anticoagulation. Since their introduction into clinical medicine over 30 years ago, both clinical and scientific evidence has demonstrated the value of oral anticoagulants in the treatment and prophylaxis of venous thrombosis. In the treatment of arterial disease, however, both the indications for and usefulness of oral anticoagulants remain very much in doubt despite their widespread use in the 1950s and 1960s and in numerous clinical trials. The initiation and continuation of oral anticoagulant therapy is a co-operative venture involving the patient, the clinician and the laboratory. The clinician must have a thorough knowledge of the indications for and contraindications to the use of these drugs, and regular, accurate laboratory control is essential if haemorrhage, the major side effect, is to be avoided or reduced to a minimum. The patient must bear the responsibility for regular clinic attendance, abstinence from proprietary medications, and must immediately seek medical advice if any sign of haemorrhage occurs.


Individual levels of plasma alpha 2-antiplasmin and alpha 2-macroglobulin during the normal menstrual cycle and in women on oral contraceptives low in oestrogen.
Determinations of alpha 2-antiplasmin and alpha 2-macroglobulin were made in plasma samples collected during one normal or hormone induced cycle in 15 normal women and 11 women using oral contraceptives containing 30 micrograms ethinyl oestradiol and 150 micrograms levo-norgestrel. The immediate plasmin inhibition test for determination of alpha 2-antiplasmin was modified for application on a centrifugal analyser using the chromogenic peptide substrate Chromozym PL. alpha 2-Macroglobulin concentration was determined by radial-immunodiffusion. There were no differences between the two groups in the mean concentrations of alpha 2-antiplasmin and alpha 2-macroglobulin, but during the cycle a slight, and statistically significant fall occurred in the alpha 2-antiplasmin concentration in both groups, while the fluctuations of alpha 2-macroglobulin were small and insignificant. Distinctly individual levels of both inhibitors were found to exist. The variations in these during the periods of the cycle fluctuated within a much narrower range than the variation of the total average. The results stress the importance of determining the fluctuations in individual levels in longitudinal studies. These findings exclude variations in the concentrations of these inhibitors as possible sources of a change in the antithrombotic potential caused by oral contraceptives.


Interaction of ACTH, corticosterone and cyclic nucleotides in Harding-Passey melanoma melanogenesis.
The acute in vitro action of adrenocorticotropin (ACTH) and corticosterone alone and in combination were determined in the Harding-Passey (HP) melanoma grown in vivo. Hormone treated melanoma dice (5--240 min) were analyzed for tyrosinase activity, cyclic AMP (cAMP) and cyclic GMP (cGMP). ACTH elevated cAMP and cGMP levels 20- and 13-fold, respectively, in the HP melanoma. However, these large increases in cyclic nucleotide levels were accompanied by only a 49% increase in tyrosinase activity. Corticosterone elicited a similar response. ACTH plus corticosterone produced an early cAMP and cGMP peak followed by depression. ACTH plus corticosterone stimulated tyrosinase activity coincident with the early cyclic nucleotide peak followed by a drop in tyrosinase activity which was subsequently elevated. The results indicate that neither cAMP nor cGMP are the sole modulators of tyrosinase activity and suggest the interaction of ACTH, corticosterone and cyclic nucleotides in the regulation of melanoma tyrosinase activity.


The Effect of Fitness Apps Usage Intensity on Exercise Adherence Among Chinese College Students: Testing a Moderated Mediation Model.
With the rapid development of media network technology, college students' exercise is influenced by the use of fitness apps. How to improve the impact of fitness apps on college students' exercise is a current research hotspot. The purpose of this study was to explore the influence mechanism of fitness apps usage intensity (FAUI) on college students' exercise adherence. A large sample of Chinese college students (N=1300) completed measures by using the FAUI Scale, Subjective Exercise Experience Scale, Control Beliefs Scale and Exercise Adherence Scale. SPSS22.0 and Hayes PROCESS macro for SPSS were used to conduct statistical analysis. (1) FAUI was positively associated with exercise adherence (p< 0.01); (2) Subjective exercise experience (p<0.01) mediated the relationship between FAUI and exercise adherence; (3) Control beliefs (p<0.01) moderated the relationship between FAUI and exercise adherence as well as subjective exercise experience and exercise adherence. The findings reveal the correlation between FAUI and exercise adherence. Furthermore, this study is important in investigating how FAUI is related to exercise adherence in Chinese college students. The results suggest that college students' subjective exercise experience and control beliefs may be prime targets for prevention and intervention programs. Thus, this study explored "how" and "when" FAUI may enhance college students' exercise adherence.


Photoresponsive dendritic azobenzene peptides.
Two dendritic peptides containing a branched lysine core and up to eight azobenzene moieties in the periphery were synthesized on solid support employing the omega-amino acid 4-(aminomethyl)phenylazobenzoic acid. With an additional peptidic tail consisting of an oligolysine portion, water solubility was achieved for the dendrimers, which allowed for the characterization of the cis/trans photoisomerization of the dendritic azobenzene species in both organic and aqueous media. Despite the interactions between the chromophores, which occur particularly in aqueous media, at higher dilution the photoisomerization process was found to proceed to extents that should permit photomodulation of molecular recognition processes between ligands grafted to the photosensitive azobenzene units and receptor molecules.


Sleep duration is associated with depressive symptoms in Chinese adolescents.
Depressive symptoms have become one of the most common mental health problems in adolescents. Identifying potential factors associated with adolescent depressive symptoms could be practical and essential for early intervention programs. The association between sleep duration and depressive symptoms in adolescents is inconsistent and needs further exploration. A total of 7330 participants aged 10-19 years were included in this study. Sleep duration was categorized into <7 h, 7-8 h, 8-9 h, and ≥ 9 h per day. The Chinese version of the Center for Epidemiology Scale for Depression was used to assess depressive symptoms. Binary logistic regression analysis was performed to evaluate the association between sleep duration and the risk of depressive symptoms. Restrictive cubic spline analyses were conducted to evaluate the dose-response relationship between sleep duration and depressive symptoms. Thirty-four percent of the participants suffered from depressive symptoms. The prevalence of depressive symptoms in adolescents with sleep durations of <7 h, 7-8 h, 8-9 h, and ≥9 h per day was 52.66 %, 37.80 %, 27.55 %, and 20.49 %, respectively. After adjusting for potential covariates, long sleep duration was significantly associated with a decreased risk of depressive symptoms in adolescents. A nonlinear relationship between sleep duration and depressive symptoms was identified. Long sleep duration is independently associated with a decreased risk of depressive symptoms in Chinese adolescents.


M.TaqI facilitates the base flipping via an unusual DNA backbone conformation.
MD simulations have been carried out to understand the dynamical behavior of the DNA substrate of the Thermus aquaticus DNA methyltransferase (M.TaqI) in the methylation process at N6 of adenine. As starting structures, an x-ray structure of M.TaqI in complex with DNA and cofactor analogue (PDB code: 1G 38) and free decamer d(GTTCGATGTC)(2) were taken. The x-ray structure shows two consecutive BII substates that are not observed in the free decamer. These consecutive BII substates are also observed during our simulation. Additionally, their facing backbones adopt the same conformations. These double facing BII substates are stable during the last 9 ns of the trajectories and result in a stretched DNA structure. On the other hand, protein-DNA contacts on 5' and 3' phosphodiester groups of the partner thymine of flipped adenine have changed. The sugar and phosphate parts of thymine have moved further into the empty space left by the flipping base without the influence of protein. Furthermore, readily high populated BII substates at the GpA step of palindromic tetrad TCGA rather than CpG step are observed in the free decamer. On the contrary, the BI substate at the GpA step is observed on the flipped adenine strand. A restrained MD simulation, reproducing the BI/BII pattern in the complex, demonstrated the influence of the unusual backbone conformation on the dynamical behavior of the target base. This finding along with the increased nearby interstrand phosphate distance is supportive to the N6-methylation mechanism.


Sex ratio and intrasexual kin competition in mammals.
Asymmetries in both intrasexual competition and generation overlap occur in Antechinus (Dasyuridae; Marsupialia). We show that the range of interpopulation variation in the sex ratio of pouch young spans and exceeds the range of sex ratios at birth hitherto recorded from eutherians (Clutton-Brock and Albon 1983). Although postweaning dispersal and male mortality are similar among all Antechinus populations, interpopulation variance in female longevity leads to variable duration of mother/daughter interaction. As this duration increases, parental investment is increasingly biased toward males, supporting the view that local competition among female kin for resources may influence mammalian sex ratios.


Attitudes of cancer patients and their families toward disclosure of cancer diagnosis in Saudi Arabia: a Middle Eastern population example.
Particularly in the Middle East, few studies have explored the attitude of cancer patients and their families toward cancer diagnosis disclosure (CDD). This study was conducted to investigate the preference and attitude of a sample of cancer patients and their families in Saudi Arabia toward CDD. We constructed a questionnaire based on previous studies. The questionnaire assessed preference and attitude toward CDD. Participants were recruited from the King Abdullah Medical City, which has one of the largest cancer centers in Saudi Arabia. Three hundred and four cancer patients and 277 of their family members participated in the study. The patient group preferred CDD more than the family group (82.6% vs 75.3%, P<0.05). This preference is especially more evident toward disclosure of detailed cancer information (status, prognosis, and treatment) (83.6% vs 59.9%, P<0.001). In a binary logistic regression, factors associated with preference toward CDD included having information about cancer (odds ratio [OR] 1.8; 95% confidence interval [CI], 1.15-2.84) and being employed (OR, 1.77; 95% CI, 1-2.82) while being from the patient group was the only factor associated with preference toward detailed cancer information (OR, 3.25; 95% CI, 2.11-5.05). In terms of patient reaction after CDD, "fear" was the attitude expected by the family group more than the patient group (56.3% vs 70.4%, P<0.001) while "acceptance" was the attitude anticipated by the patient group more than the family group (38% vs 15.2%, P<0.001). Patients preferred CDD and disclosure of related information, while their families were more inclined toward scarce disclosure. Family members seem to experience negative attitudes more than the patients themselves.


A Novel Oral Fluid Assay (LC-QTOF-MS) for the Detection of Fentanyl and Clandestine Opioids in Oral Fluid After Reported Heroin Overdose.
The adulteration of heroin with non-pharmaceutical fentanyl and other high-potency opioids is one of the factors contributing to striking increases in overdose deaths. To fully understand the magnitude of this problem, accurate detection methods for fentanyl and other novel opioid adulterant exposures are urgently required. The objective of this work was to compare the detection of fentanyl in oral fluid and urine specimens using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) in a population of heroin users presenting to the Emergency Department after overdose. This was a prospective observational study of adult Emergency Department patients who presented after a reported heroin overdose requiring naloxone administration. Participants provided paired oral fluid and urine specimens, which were prepared, extracted, and analyzed using a dual LC-QTOF-MS workflow for the identification of traditional and emerging drugs of abuse. Analytical instrumentation included SCIEX TripleTOF® 5600+ and Waters Xevo® G2-S QTOF systems. Thirty participants (N = 30) were enrolled during the study period. Twenty-nine participants had fentanyl detected in their urine, while 27 had fentanyl identified in their oral fluid (overall agreement 93.3%, positive percent agreement 93.1%). Cohen's Kappa (k) was calculated and demonstrated moderately, significant agreement (k = 0.47; p value 0.002) in fentanyl detection between oral fluid and urine using this LC-QTOF-MS methodology. Additional novel opioids and metabolites, including norfentanyl, acetylfentanyl, and U-47700, were detected during this study. In this study of individuals presenting to the ED after reported heroin overdose, a strikingly high proportion had a detectable fentanyl exposure. Using LC-QTOF-MS, the agreement between paired oral fluid and urine testing for fentanyl detection indicates a role for oral fluid testing in surveillance for nonpharmaceutical fentanyl. Additionally, the use of LC-QTOF-MS allowed for the detection of other clandestine opioids (acetylfentanyl and U-47700) in oral fluid.


Transcriptome analysis of the pearl oyster (Pinctada fucata) hemocytes in response to Vibrio alginolyticus infection.
The pearl oyster Pinctada fucata is cultured widely for production of marine pearls in China, while mass mortalities, likely related to pathogenic infections, have occurred frequently in juvenile, mother and operated oysters. To address this issue, understanding host defense mechanisms of P. fucata against pathogenic challenge is extremely important. In the present study, a comparative analysis of hemocyte transcriptomes of P. fucata before and after Vibrio alginolyticus infection was conducted using the Illumina/Hiseq-2000 RNA-Seq technology. A total of 56,345,139 clean reads were generated and then assembled into 74,007 unigenes with an average length of 680 bp and an N50 of 1197 bp. Unigenes were annotated by comparing against non-redundant protein sequence (nr), non-redundant nucleotide (nt), Swiss-Prot, Pfam, Gene Ontology database (GO), Clusters of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and 29,615 unigenes (40.01%) were annotated in at least one database. There were 636 genes (518 up-regulated and 118 down-regulated) that were significantly differentially expressed after bacterial challenge, and among which 369 were associated with 122 pathways, including classical immune-related pathways, such as 'MAPK signaling pathway', 'Chemokine signaling pathway', 'Apoptosis' and 'Wnt signaling pathway'. These findings provide information on the pearl oyster innate immunity and may contribute to developing strategies for management of diseases and long-term sustainability of P. fucata culture.


Control over the preference for binding sites of polyoxometalates to silver ethynide clusters by surface charge modification.
A polyoxometalate-silver ethynide composite cluster, [Ag42(CO3){C≡CC(CH3)3}27(α-A-SiW9Nb3O40)2](-) (1), demonstrates that we can select the binding site of a polyoxometalate to the silver alkynide cluster by tuning the surface charge of the precursor polyoxometalate. Multidimensional and multinuclear NMR spectra revealed that 1 maintains its precise atomic connectivity in the solution.