Volatile organic compounds of conspecific-damaged Eucalyptus benthamii influence responses of mated females of Thaumastocoris peregrinus.
Plants respond to herbivory by synthesizing and releasing novel blends of volatile organic compounds (VOCs). Natural enemies are attracted to these VOCs, but little is known about the effects of these chemicals on the herbivores themselves. We studied the effect of Thaumastocoris peregrinus herbivory on VOCs released by Eucalyptus benthamii plants and the responses of this herbivore to the VOCs. In total, 12 compounds released by E. benthamii were identified. Five compounds (β-pinene, linalool, 9-epi-(E)-caryophyllene, viridiflorol, and one unidentified compound) emitted after herbivore and mechanical damage were not detected in collections from undamaged plants. The three most abundant VOCs, α-pinene, aromadendrene, and globulol, were released in greater quantities from herbivore-damaged plants compared to plants with mechanical damage, which, in turn, released greater amounts than undamaged (control) plants. The VOCs emitted after herbivore damage did not differ during the photophase and scotophase in either quantity or quality. In an olfactometer, mated female T. peregrinus showed a preference for undamaged plants over herbivore-damaged plants, and also for hexane over α-pinene at an amount equivalent to that released by a herbivore-damaged plant. In the olfactometer, virgin females did not exhibit any preference between conspecific-damaged or undamaged plants.


The effect of discharge care plans on statin prescription rates.
Stroke discharge care bundles have been proposed to address inadequate provider statin prescription rates. Discontinuation of statins has been associated with a 37% relative risk increase in mortality in patients with a stroke diagnosis. The project site had a statin prescription rate of 86.2%. The project was initiated at a 641-bed regional community teaching medical center. Statin prescription rates upon discharge on patients with the diagnosis of transient ischemic attack or stroke were evaluated and noted to be below the benchmark of 95%. Possible interventions to improve this benchmark were discussed with key stakeholders such as the information technology team, stroke care outcomes team, and neurology service providers. The proposed intervention was incorporated into the electronic health record. Provider prescription rates were tracked monthly along with the use of the proposed intervention. A one-sided z-test was used to analyze the data collected. A stroke discharge power plan within an electronic health record was modified to increase the rate of statin prescriptions. The key modification included checking off the prescription of a statin on discharge. Reinforcement of its use was done through monthly reminders. Use of discharge care plan yielded 100% compliance. Overall compliance was 9.7%. The null hypothesis of the one-sided z-test was 89%. The p -value for all tests was <0.05. The use of a stroke discharge care plan within an electronic health record can positively affect secondary stroke prevention by increasing statin prescription rates.


Efficacy of platelet rich fibrin in the reduction of the pain and swelling after impacted third molar surgery: randomized multicenter split-mouth clinical trial.
Impacted third molar removal is a routine procedure in oral and maxillofacial surgery. Platelet-rich fibrin (PRF) is a second generation platelet concentration which is produced by simplified protocol. The aim of this study was to assess the effectiveness of PRF in the healing process by evaluating the changes in pain and swelling after third molar surgery. Fifty-six patients (23 male, 33 female) who provide the inclusion criteria were selected to participate in this study. The evaluation of the facial swelling was performed by using a horizontal and vertical guide. The pain was evaluated in the postoperative period using a visual analog scale (VAS) of 100 mm. Horizontal and vertical measurements showed more swelling at the control side (without PRF) in 3th day postoperatively (p < 0.05). There were no statistically significant differences regarding pain among the groups. As a conclusion, PRF seems to be effectiveness on postoperative horizontal swelling after third molar surgery. PRF could be used on a routine basis after third molar extraction surgery.


Succinate dehydrogenase deficient renal cell carcinoma: A case report.
Succinate dehydrogenase (SDH) deficient renal cell carcinoma (RCC) are uncommon renal tumors that typically present in relatively younger patients. SDH mutations are known to cause cancer, but often presents with hereditary paragangliomas, pheochromocytomas, and gastrointestinal stromal tumors. This report details a case of SDH deficient RCC in a patient with no know contributing family history. Patient presented with recurrent urinary tract infections and groin pain. Computerized tomography (CT) revealed a 4 cm mass in the right kidney. Partial nephrectomy was performed, and the patient had an uneventful recovery. Immunohistochemical staining revealed the tumor was SDH negative.


Photoelectrochemical Nitrate Reduction to Ammonia on Ordered Silicon Nanowire Array Photocathodes.
As a new path to "green" ammonia production, photoelectrochemical nitrate reduction reaction (PEC NO3 RR) is investigated for the first time. An Au-decorated ordered silicon nanowire (O_SiNW) array photocathode demonstrates 95.6 % of Faradaic efficiency (FE) to ammonia at 0.2 VRHE , which represents a more positive potential than the thermodynamic reduction potential of nitrate by utilizing photovoltage. The high FE is possible because both Si and Au surfaces are inactive for competing water reduction to hydrogen. The O_SiNW array structure is favorable to promote the PEC NO3 RR relative to planar Si or randomly-grown Si nanowire, by enabling the uniform distribution of small Au nanoparticles as an electrocatalyst and facilitating the mass transport during the reaction. The results demonstrate the feasibility of PEC nitrate conversion to ammonia and would motivate further studies and developments.


The changing patterns of cardiovascular diseases and their risk factors in the states of India: the Global Burden of Disease Study 1990-2016.
The burden of cardiovascular diseases is increasing in India, but a systematic understanding of its distribution and time trends across all the states is not readily available. In this report, we present a detailed analysis of how the patterns of cardiovascular diseases and major risk factors have changed across the states of India between 1990 and 2016. We analysed the prevalence and disability-adjusted life-years (DALYs) due to cardiovascular diseases and the major component causes in the states of India from 1990 to 2016, using all accessible data sources as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016. We placed states into four groups based on epidemiological transition level (ETL), defined using the ratio of DALYs from communicable diseases to those from non-communicable diseases and injuries combined, with a low ratio denoting high ETL and vice versa. We assessed heterogeneity in the burden of major cardiovascular diseases across the states of India, and the contribution of risk factors to cardiovascular diseases. We calculated 95% uncertainty intervals (UIs) for the point estimates. Overall, cardiovascular diseases contributed 28·1% (95% UI 26·5-29·1) of the total deaths and 14·1% (12·9-15·3) of the total DALYs in India in 2016, compared with 15·2% (13·7-16·2) and 6·9% (6·3-7·4), respectively, in 1990. In 2016, there was a nine times difference between states in the DALY rate for ischaemic heart disease, a six times difference for stroke, and a four times difference for rheumatic heart disease. 23·8 million (95% UI 22·6-25·0) prevalent cases of ischaemic heart disease were estimated in India in 2016, and 6·5 million (6·3-6·8) prevalent cases of stroke, a 2·3 times increase in both disorders from 1990. The age-standardised prevalence of both ischaemic heart disease and stroke increased in all ETL state groups between 1990 and 2016, whereas that of rheumatic heart disease decreased; the increase for ischaemic heart disease was highest in the low ETL state group. 53·4% (95% UI 52·6-54·6) of crude deaths due to cardiovascular diseases in India in 2016 were among people younger than 70 years, with a higher proportion in the low ETL state group. The leading overlapping risk factors for cardiovascular diseases in 2016 included dietary risks (56·4% [95% CI 48·5-63·9] of cardiovascular disease DALYs), high systolic blood pressure (54·6% [49·0-59·8]), air pollution (31·1% [29·0-33·4]), high total cholesterol (29·4% [24·3-34·8]), tobacco use (18·9% [16·6-21·3]), high fasting plasma glucose (16·7% [11·4-23·5]), and high body-mass index (14·7% [8·3-22·0]). The prevalence of high systolic blood pressure, high total cholesterol, and high fasting plasma glucose increased generally across all ETL state groups from 1990 to 2016, but this increase was variable across the states; the prevalence of smoking decreased during this period in all ETL state groups. The burden from the leading cardiovascular diseases in India-ischaemic heart disease and stroke-varies widely between the states. Their increasing prevalence and that of several major risk factors in every part of India, especially the highest increase in the prevalence of ischaemic heart disease in the less developed low ETL states, indicates the need for urgent policy and health system response appropriate for the situation in each state. Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India.


[Hearing aid provision in children].
Achieving high-quality hearing aid fitting in children is an interdisciplinary task and a challenge for all involved specialist disciplines. According to quality agreements (standards), comparative hearing aid fitting is mandatory prior to prescription. Furthermore, RECD measurements and, in older children, in-situ measurements should be applied on a regular basis for finetuning and adjustment of the hearing aid fitting. ENT physicians, phoniatricians and pediatric audiologists, pediatric acousticians, teachers of the hearing impaired, and special educational needs teachers should work together in an interdisciplinary approach.


Efficiency measurement of health care: a review of non-parametric methods and applications.
There has been increasing interest in measuring the productive performance of health care services, since the mid-1980s. This paper reviews this literature and, in particular, the concept and measurement of efficiency and productivity. Concerning measurement, we focus on the use of Data Envelopment Analysis (DEA), a technique particularly appropriate when multiple outputs are produced from multiple inputs. Applications to hospitals and to the wider context of general health care are reviewed and the empirical evidence from both the USA and Europe (EU) is that public rather than private provision is more efficient.


Risk factors for eclampsia in Japan between 2005 and 2009.
To determine risk factors for eclampsia among Japanese women with singleton pregnancies. A retrospective observational study was carried out among patients with and those without eclampsia who were registered on the Japan Society of Obstetrics and Gynecology registry system and who gave birth to singleton infants at 22 weeks or more between 2005 and 2009. Multivariate logistic regression analyses were performed to determine independent risk factors for eclampsia. One-third (75/225) of eclampsia patients developed the condition in the absence of hypertension. Maternal age, nulliparity, and pregnancy-induced hypertension (PIH) were all independent risk factors for eclampsia. The risk of eclampsia decreased by 3.0% per 1-year increase in maternal age, and increased 2.6-fold and 35.4-fold in nulliparous women and women with PIH, respectively. Among teenaged girls with hypertension, the prevalence of eclampsia was 1 case per 28 teenagers. Hypertension alone was not a reliable predictor of eclampsia. More intensified monitoring of nulliparous women and teenaged girls with hypertension is needed in order to prevent eclampsia.


[Angiotensin-converting enzyme inhibitor treatment of heart failure due to dilated cardiomyopathy].
To assess effects of enalapril and Accupro on clinical status left ventricular remodeling and systolic function in patients with heart failure due to dilated cardiomyopathy. Randomized, open, controlled, duration -- 6 months. 31 patients with dilated cardiomyopathy (mean age 46+/-2 years). Standard therapy (glycosides, diuretics, peripheral vasodialtors) -- 9 patients. Standard therapy plus enalapril (10-20 mg/day) - 11 patients; standard therapy plus accupro (slow titration from 5 to a maximum 20 mg/day)-- 11 patients. NyHa functional class, 6 -- minute wall test, echocardiographical parameters of left ventracular systolic function, while some parameters of remodeling deteriorated. Standard therapy did not change clinical status or left ventrical systolic function, while some parameters of remodeling deteriorated. Enalapril improved clinical status, left ventricular systolic function and affected favorably left ventricular remodeling. Accupro compared with enalapril produces greater influence on left ventricular remodeling. Our study suggests that intrinsic differences exist between quinaprilat and enalaprilat that determine the ability to improve endotelium vasodilation, their different affinity to tissue ACE.


[Treatment of macular edema: Comparison of efficacy and tolerability of subconjunctival triamcinolone injections, sub-tenon's triamcinolone injections and intravitreal dexamethasone implant].
The area of uveitis is related to numerous pathological entities. One of the main causes of decreased visual acuity in these patients is macular edema. One aspect of the treatment includes cortosteroids used peri- and intra-ocularly. The goal of our work was to estimate the criteria of efficacy (on improvement in visual acuity and macular edema, as well as time to recurrence) and safety (on intraocular pressure and cataract) of these various routes of administration of corticosteroid after a single injection. We compared patients treated with Ozurdex® versus subconjonctival triamcinolone versus sub-tenon's triamcinolone. This is a retrospective study conducted in 2 tertiary centers, the university medical center of Nantes and La Pitié-Salpêtrière hospital from November, 2011 to November, 2013. At presentation, 25 % of the patients displayed VA better than 5/10. During follow-up, this proportion increased to 45 % at M1, 50 % at M3, 49 % at M6 and 48 % at the end of follow-up. There was no significant difference between the groups with respect to VA gain. The reductions in mean CMT compared with D0 were all statistically significant (improvement of one line in log-OCT). We observed an improvement in macular thickness of 88 % at M1, 86 % at M3, 61 % at M6 and 60 % at the end of follow-up, significant at each time, with no significant difference between the three groups. A comparison of time to anatomic vs. functional recurrence was performed, showing no difference. The largest increase in IOP was observed at M1, statistically different from the other time points. Intra- and periocular injections should be considered as an adjuvant therapy, since the majority of the conditions in question require systemic treatment. They allow for increased intravitreal concentrations with fewer systemic effects. We demonstrated neither any true superiority of any of the 3 treatments nor any difference in tolerability between the 3 groups.


Doxorubicin-antioxidant co-drugs.
Doxorubicin-antioxidant multitarget compounds 6 and 7 were obtained by combining doxorubicin (DOX) with caffeic and ferulic acids through an ester linkage at C-14. The products were studied in in vitro models of cardiomyocytes and breast cancer cells, characterized by different degrees of resistance to DOX, due to different expressions of ATP binding cassette (ABC) transporters. Compound 7 was found to be less toxic than DOX in cardiomyocytes and to display the same possibly higher toxicity against the resistant breast cancer cells. This result shows that appropriate DOX-antioxidant co-drugs can limit the onset of cardiac damage, a significant side-effect of DOX, without impairing the antitumor activity of the parent antibiotic.


Classifying Regularized Sensor Covariance Matrices: An Alternative to CSP.
Common spatial patterns (CSP) is a commonly used technique for classifying imagined movement type brain-computer interface (BCI) datasets. It has been very successful with many extensions and improvements on the basic technique. However, a drawback of CSP is that the signal processing pipeline contains two supervised learning stages: the first in which class- relevant spatial filters are learned and a second in which a classifier is used to classify the filtered variances. This may lead to potential overfitting issues, which are generally avoided by limiting CSP to only a few filters.


The African experience: a proposal to address the lack of access to neurosurgery in rural sub-Saharan Africa.
Restricted access to neurosurgical care in rural sub-Saharan Africa remains an unaddressed and formidable challenge. Despite the implementation of a rigorous 5-year curriculum to train and certify indigenous neurosurgeons "in continent" as Fellows of the College of Surgeons in Neurosurgery for East, Central, and Southern Africa (FCS-ecsa-NS), provincial and rural hospitals are likely to see no change in this woeful status quo for the foreseeable future. Modifying that curriculum with a two-tiered training experience that includes fast-track certification of general surgeons to perform basic neurosurgical procedures in their own hospitals is a viable alternative to redress this problem in a timely fashion. Founded on a competence-based as opposed to a time-served assessment of clinical/surgical skills along the lines of a 2002 landmark study in the United Kingdom, such an approach (in tandem with retaining separate FCS certification for prospective faculty in the NSTP-ECSA program) deserves urgent reconsideration.


Staphylococcus aureus isolates with reduced susceptibility to glycopeptides belong to accessory gene regulator group I or II.
We used multiplex PCR to determine the agr group membership of 18 European glycopeptide heterointermediate and intermediate-resistant Staphylococcus aureus strains. Of the 15 agr group I strains, 13 were resistant and 2 were susceptible to methicillin. The remaining three strains, like the United States and Japanese control strains, belonged to agr group II.


Tetragonal phase of epitaxial room-temperature antiferromagnet CuMnAs.
Recent studies have demonstrated the potential of antiferromagnets as the active component in spintronic devices. This is in contrast to their current passive role as pinning layers in hard disk read heads and magnetic memories. Here we report the epitaxial growth of a new high-temperature antiferromagnetic material, tetragonal CuMnAs, which exhibits excellent crystal quality, chemical order and compatibility with existing semiconductor technologies. We demonstrate its growth on the III-V semiconductors GaAs and GaP, and show that the structure is also lattice matched to Si. Neutron diffraction shows collinear antiferromagnetic order with a high Néel temperature. Combined with our demonstration of room-temperature-exchange coupling in a CuMnAs/Fe bilayer, we conclude that tetragonal CuMnAs films are suitable candidate materials for antiferromagnetic spintronics.


Heterometallic manganese/zinc-phytate complex as a model compound for metal storage in wheat grains.
Myo-inositol-1,2,3,4,5,6-hexakisphosphate, also known as phytate, is a natural metal chelate present in cereals, an important feedstock worldwide. This article reports the characterization of three metal storage model complexes: the homometallic Mn(II) myo-inositol-1,2,3,4,5,6-hexakisphosphate (IP6), the heterometallic Zn(II), Mn(II) analogue Na4MnZn4(C6H6O24P6) x (NO3)2 x 8H2O (MnZn4IP6) and the homometallic Zn(II) metal complex Na3Zn5(C6H6O24P6)OH x 9H2O (Zn5IP6). The techniques of high-resolution 23Na, 13C and 31P NMR, electron paramagnetic resonance (EPR) and X-ray photoelectron spectroscopy (XPS) were applied in this study. The complexation of Zn(II) and Mn(II) by phosphate groups of IP6 is demonstrated by NMR and XPS results. 13C NMR results show a conformation for IP6 consisting of five equatorial phosphate groups to one axial group showing only one chemical environment for Zn and two for Mn, when characterized by XPS and EPR, in both Mn complexes. These results support, for the first time, a probable supramacromolecular structure for phytate complexes of transition metals. Based on the similarity between the EPR spectra of wheat seeds and that of the MnZn4IP6 compound, the manganese storage centers in wheat grains can be assigned to similar heterometallic phytate complexes.


Physiological Assessment of Muscle, Heart, and Whole Body Function in the Canine Model of Duchenne Muscular Dystrophy.
Duchenne muscular dystrophy (DMD) is a lethal muscle disease caused by dystrophin deficiency. Patients gradually lose motor function, become wheelchair-bound, and die from respiratory and/or cardiac muscle failure. Dystrophin-null dogs have been used as a large animal model for DMD since 1988 and are considered an excellent bridge between rodent models and human patients. While numerous protocols have been published for studying muscle and heart physiology in mice, few such protocols exist for studying skeletal muscle contractility, heart function, and whole-body activity in dogs. Over the last 20 years, we have developed and adapted an array of assays to evaluate whole-body movement, gait, single muscle force, whole limb torque, cardiac electrophysiology, and hemodynamic function in normal and dystrophic dogs. In this chapter, we present detailed working protocols for these assays and lessons we learned during the development and use of these protocols.


Congenital hemifacial hypertrophy. Report of two cases.
Two cases of congenital hemifacial hypertrophy are described. To our knowledge, this is the first report of this syndrome in a black African population. Possible diagnostic problems are highlighted.


Preservation of RNA for functional analysis of separated alleles in yeast: comparison of snap-frozen and RNALater solid tissue storage methods.
The aim of the present study was to compare RNALater with the usual method of liquid nitrogen snap freezing as a surrogate mRNA preservation method for functional analysis of separated alleles in yeast (FASAY). A total of 81 patients with transitional cell carcinoma of the bladder underwent fresh tissue biopsies directly transferred into RNALater and stored at room temperature or at 4 degrees C for increasing time intervals until RNA processing. From this cohort of patients, 53 paired snap-frozen and RNALater preservative-suspended tissues were obtained. Samples immediately frozen in liquid nitrogen were further stored at -80 degrees C. Of the 81 RNALater samples, 14 were not processed for FASAY because of RNA degradation. Of the remaining 67 samples, 15 (22%) were FASAY-positive. Identical FASAY results were found for 50 of 53 (94.4%) paired samples and the percentage of red yeast colonies was highly correlated (Cohen's kappa<0.82; p<0.00001). A single p53 missense mutation was found in each of the three discordant positive FASAY and was identical in each concordant positive sample (10/53). Storing samples in RNALater at room temperature for 3 days and at 4 degrees C for less than 1 month provided high-quality mRNA suitable for FASAY. Our results demonstrate that RNALater is a suitable and flexible alternative to snap freezing for FASAY analysis.


Gender Differences in the Association between Adverse Childhood Experiences and Cancer.
Adverse childhood experiences (ACEs) have been linked to a variety of diseases in adulthood, including cancer. However, current research has yet to determine if all abuse types are associated with cancer and if women are more adversely impacted by ACEs than men. Data from the 2011 Behavioral Risk Factor Surveillance System, a national survey of American adults 18 and older (N = 111,964) were analyzed. Logistic regression models were fit to estimate odds of ever being diagnosed with cancer after experiencing one or more of eight different ACEs, while adjusting for potential confounders. These analyses were then stratified by gender. Among women, childhood experiences of physical abuse, sexual abuse, emotional abuse, living with someone who was mentally ill, living with a problem drinker, living with a drug user, and living in a household where adults treated each other violently were associated with higher odds of cancer. Among men, only emotional abuse was associated with higher odds of cancer. Results suggest that ACEs increase risk of cancer later in life. However, this impact occurs mostly among women. This finding may be because women experience many ACEs at higher rates than men and because women, via sexual abuse, can be exposed to cancer-causing viruses.


Evaluating the Contribution of Cell Type-Specific Alternative Splicing to Variation in Lipid Levels.
Genome-wide association studies have identified hundreds of loci associated with lipid levels. However, the genetic mechanisms underlying most of these loci are not well-understood. Recent work indicates that changes in the abundance of alternatively spliced transcripts contribute to complex trait variation. Consequently, identifying genetic loci that associate with alternative splicing in disease-relevant cell types and determining the degree to which these loci are informative for lipid biology is of broad interest. We analyze gene splicing in 83 sample-matched induced pluripotent stem cell (iPSC) and hepatocyte-like cell lines (n=166), as well as in an independent collection of primary liver tissues (n=96) to perform discovery of splicing quantitative trait loci (sQTLs). We observe that transcript splicing is highly cell type specific, and the genes that are differentially spliced between iPSCs and hepatocyte-like cells are enriched for metabolism pathway annotations. We identify 1384 hepatocyte-like cell sQTLs and 1455 iPSC sQTLs at a false discovery rate of <5% and find that sQTLs are often shared across cell types. To evaluate the contribution of sQTLs to variation in lipid levels, we conduct colocalization analysis using lipid genome-wide association data. We identify 19 lipid-associated loci that colocalize either with an hepatocyte-like cell expression quantitative trait locus or sQTL. Only 2 loci colocalize with both a sQTL and expression quantitative trait locus, indicating that sQTLs contribute information about genome-wide association studies loci that cannot be obtained by analysis of steady-state gene expression alone. These results provide an important foundation for future efforts that use iPSC and iPSC-derived cells to evaluate genetic mechanisms influencing both cardiovascular disease risk and complex traits in general.


Hot-Injection Synthesis of HgTe Nanoparticles: Shape Control and Growth Mechanisms.
Understanding the growth mechanisms of HgTe nanoparticles (NPs) with varied shapes is crucial for their applications in infrared photodetection. Here, we investigated the growth mechanisms of HgTe NPs with nanorod, sphere, and tetrahedral shapes in depth. The HgTe NPs with a nanorod shape are obtained at low reaction temperatures and formed by breaking tetrapod branches, while HgTe NPs with sphere and tetrahedron shapes have been further achieved at increased reaction temperatures. The systematic crystal analyses demonstrate this effective shape control is related to the synergic effect among the anisotropic passivation of oleylamine, surface free energy, and reaction temperatures. Our findings have deepened the understanding of shape control of the HgTe NPs and inspired a growing passion in the design and engineering of infrared photodetectors using HgTe NPs.


Sub-lethal acute effects of environmental concentrations of inorganic mercury on hematological and biochemical parameters in walking catfish, Clarias batrachus.
The acute toxicity of mercury to the air-breathing fish Clarias batrachus (Linn.) was determined in this study using hematological (including hemoglobin, hematocrit, total erythrocyte count, total leukocyte count, and mean corpuscular hemoglobin concentration) and biochemical (including total serum protein, serum glucose, triglyceride, cholesterol, albumin) biomarkers at predetermined exposure concentrations (0.069 and 0.139 mg/L). Although significant differences were observed between exposure groups for all hematological and biochemical variables, a distinctive reduction in hemoglobin levels, hematocrit, and total erythrocyte count in the mercury-exposed fish compared to the control was observed from 24 h-96 h. Similarly, marked differences in serum globulin, total serum protein and cholesterol levels were observed across exposure groups from 24 h-96 h. While the marked hematological responses strongly suggestive of toxicant-related anemia, the marked biochemical responses suggest immune-modulation and metabolic disruption. The magnitude of toxic effects under graded toxicant exposures for weighted scores of combined biomarker response index (IBR) indicated an approximately 3-fold deterioration in overall health of mercury-exposed fish compared to control group. Depictions of hematological and biochemical effects in hardy species like Clarias batrachus indicate an imminent onset of anemia, immune-modulation and metabolic disruption within 24hs of exposure to inorganic mercury. Such observations for portends greater deleterious effects to less hardy aquatic biota under acute inorganic mercury environmental exposures.


Polymorphisms in multiple genes are associated with resting heart rate in a stepwise allele-dependent manner.
The purpose of this study was to use a candidate gene approach to identify common polymorphisms that are associated with resting sinus heart rate in a population without overt cardiovascular disease. Increased resting heart rate is significantly associated with susceptibility to development of myocardial infarction, sudden cardiac death, and overall cardiac mortality. A longitudinal cohort of 1468 individuals (active and retired middle-aged Canadian firefighters) who were enrolled in the Firefighters and Their Endothelium (FATE) study was evaluated. Resting heart rate was recorded from the electrocardiogram (ECG) obtained at enrollment. Candidate genes were selected for their known roles in sinus node automaticity and/or its regulation, and single nucleotide polymorphisms (SNPs) with a minor allele frequency of > or =0.20 were targeted. A total of 53 SNPs in 46 genes were selected and analyzed in a screening sample, and 33 SNPs in 29 genes were evaluated in the full population. Univariate analysis detected five putative associations between HR and SNPs. As expected, environmental covariates were identified. Three polymorphisms, ADRB1 G389R, SCN5a H558R, and CASQ1 intron 2, remained statistically significant and independent of covariates. Some alleles were associated with higher and some with lower heart rates. A stepwise increase in heart rate was observed that was dependent on the number of tachycardia-associated alleles with progressive increases in mean heart rate from 51 to 66 bpm. Common polymorphisms are associated with heart rate in a stepwise allele-dependent manner.


Neurokinin 1 receptor antagonism promotes active stress coping via enhanced septal 5-HT transmission.
Antagonists of the substance P (SP) preferring neurokinin 1 receptor (NK1R) represent a promising novel class of drugs for the treatment of stress-related disorders such as depression and anxiety disorders; however, the involved neuronal pathways releasing SP in response to stressors are ill defined. By using in vivo microdialysis in combination with a highly sensitive and selective radioimmunoassay we found that exposure to forced swim stress increased SP release in the rat lateral septum (LS), a key area in processing emotions and stress responses. Acute administration of the selective NK1R antagonist L-822429 injected either systemically or locally into the LS reduced passive and facilitated active stress-coping strategies in the forced swim test. This effect seems to be mediated by enhanced intraseptal serotonergic transmission via serotonin (5-HT)1A receptors since NK1R blockade reversed the swim stress-induced decrease to an increase in extracellular 5-HT efflux, and furthermore the behavioral effects of L-822429 were blocked by intraseptal 5-HT1A receptor antagonism. A direct heterosynaptic regulation by NK1R on 5-HT release from serotonergic fibers was ruled out by immunocytochemistry at the light and electron microscopic level indicating involvement of GABAergic interneuron(s) in this interaction. Taken together, our data identify the LS as a critical brain area for the involvement of SP transmission in the modulation of stress responses and demonstrate that NK1R blockade can elicit a functionally significant facilitatory effect on 5-HT transmission, which does not necessarily involve the previously proposed interaction with neuronal firing at the cell body level of raphe neurons.


Evaluation of the effect of basil seed gum, tragacanth gum, pectin, and coating formulation with corn flour on oil absorption and sensory properties of watermelon rind chips.
The current study aims to produce coated watermelon rind chips with the approach of reducing oil absorption and optimal use of waste and investigating its physicochemical, textural, and sensory characteristics. The effect of coating with basil seed gum, Tragacanth gum, pectin, and coating formulation with corn flour on oil absorption rate, moisture loss, and color of white skin slices of fried watermelon was studied. The results indicated that due to the controlling role of water in the amount of oil absorption, the amount of oil in all the samples coated with gum and corn flour was decreased compared to the samples coated with gum and the samples without coating. The pretreatment of osmotic dehydration reduces oil absorption in compared to fresh and blanched samples. The color changes in the sample with two pre-treatments of osmosis and blanching were less than other samples, as a result, the brightness of this sample was also higher than others. The lowest amount of oil absorption was observed in samples coated with basil gum and 0.5% and 1% corn flour (0.33 and 0.29, respectively). The highest amount of moisture loss during frying was related to the coated samples was observed with the combination of basil gum and corn flour (0.5%) and pectin and corn flour (2%). The highest level of antioxidant activity of the fried samples was related to the sample coated with 0.5% basil gum. Significant color changes were also observed in the coated samples.


Disgust propensity and sensitivity in childhood anxiety and obsessive-compulsive disorder: Two constructs differentially related to obsessional content.
The role of disgust in anxiety and related disorders has been extensively studied in adults, however its role in childhood psychopathology is in need of further investigation. The adult literature has suggested that two distinct sub-constructs within "disgust proneness" may differentially predict anxiety-related disorders. Namely, disgust propensity (DP) has been defined as the likelihood an individual will experience a disgust reaction, and disgust sensitivity (DS) as the degree to which an individual is distressed by their experience of disgust. The current study aimed to validate the Disgust Propensity and Sensitivity Scale-Revised (DPSS-R) in a sample of youth receiving intensive services for OCD and anxiety, examine the relationship between disgust sub-constructs and obsessional content in a sample of youth with OCD, and examine the relationship between disgust change and symptom severity at discharge. A confirmatory factor analysis supported a two-factor structure of the DPSS-R. DP was found to be uniquely predictive of contamination obsessions, and DS was found to be uniquely predictive of moral obsessions. Lastly, change in DP, but not DS, predicted overall change in OCD symptom severity. The present study provides a valid measure of DS and DP in youth with anxiety and related disorders, and suggests that subconstructs of disgust may serve as distinct risk factors for obsessional content in youth with OCD. Future research should examine the predictive validity of DP and DS longitudinally, as well as examine effective ways to more effectively target DP with exposure therapy.


Perception of motion and qEEG activity in human adults.
This study was designed to relate visual perception of motion to cortical activity, by evaluation of the association of quantified electroencephalogram (qEEG) parameters with a video film projection. The EEG was recorded from 14 sites according to the International 10-20 system and a common average reference was used. Forty right-handed volunteers (mean age = 24 years) were examined. The video film consisted of 20 s sequences showing still shots and moving shots with human movements or object movements. The EEG was then subjected to spectral analysis; the spectral powers for the theta, alpha and beta bands were calculated for 14 s epochs and compared with sequences of the video film. All analyses were based on logarithmically transformed absolute spectral power values. The power values of each frequency band were analysed in a 3-way repeated measure ANOVA (Hemisphere x Electrode x Sequence). The results were represented by EEG cartography. Significant decreases in the alpha 1, beta 1 and beta 2 power values of EEG in centro-parietal regions of both hemispheres were shown during perception of human motion sequences. This suggests participation of the sensorimotor cortex during visual observation of human motion.


High temperature liquid chromatography and liquid chromatography-mass spectroscopy analysis of octylphenol ethoxylates on different stationary phases.
Temperature was investigated as active parameter in the liquid chromatography (LC) analysis of octylphenol ethoxylates. Significant differences in selectivity were observed when the oligomers were analyzed by reversed phase LC (RPLC) on silica-, zirconia- and polystyrene/divinylbenzene based stationary phases at low (ambient), medium and elevated temperature with acetonitrile/water as mobile phase. As ascertained by LC-mass spectroscopy (MS), in most cases the elution order of the oligomers was completely reversed comparing ambient and high temperature separations. On a graphitized carbon type column, the selectivity remained unchanged, regardless the analysis temperature. Also in normal phase LC, the elution order remained unaffected by temperature variations both for acetonitrile/water and methanol/water mixtures as mobile phase. Surprisingly, when reversed phase LC on a octadecylsilicagel column at different temperatures was repeated with methanol instead of acetonitrile as mobile phase ingredient, the reversal of elution order did not take place. Results are evaluated in terms of thermodynamic parameters.


Exposure to Toxocara spp. and Ascaris lumbricoides infections and risk of allergic rhinitis in children.
Substantial experimental studies suggest a role for helminthes infections in the pathogenesis of allergies, but epidemiologic data have been inconsistent. Unlike to asthma, the association between helminthes infection and allergic rhinitis (AR) has been poorly studied. Therefore, we sought to evaluate the association between exposure to Ascaris and Toxocara infections and AR. We did an age- and gender-matched case-control study of 81 children with physician-confirmed AR and 101 control subjects in a referral hospital for pediatric diseases in northern Iran. Exposure to Ascaris and Toxocara infections was evaluated by anti-A. lumbricoides- and anti-Toxocara- IgG antibodies using a commercial enzyme-linked immunosorbent assay. Associations were determined using multivariate logistic regression. Ascaris seropositivity was higher in children with rhinitis than in controls (12.34 vs. 3.96%). Ascaris seropositivity was positively associated with AR in univariate analysis (OR, 3.42; 95% CI 1.03-11.3; P value = 0.035), but this association was not significant after adjustment for potential confounders (OR, 1.85; 95% CI 0.42-8.18). Also Toxocara seropositivity was higher in children with AR than in healthy subjects (3.7% vs. 0.99), indicating non-significant association with AR in both univariate (OR, 3.84; 95% CI 0.39-37.7) and multivariate analyses (OR, 0.8; 95% CI 0.04-15.44). Our results revealed that AR is not associated with seropositivity to Ascaris and Toxocara infections in general; however, a higher seropositivity rate was found for both parasites in children with AR. More studies with longitudinal design and larger sample size are needed to elucidate this association.


In defense of Pierre Louis who pioneered the epidemiological approach to good medicine.
Pierre Louis, in his 1836 publication, "Researches on the effects of bloodletting in some inflammatory diseases," concluded that there were "narrow limits to the utility" of bloodletting for the treatment of pneumonia. Louis's conclusions were based on an observed excess mortality of patients bled rapidly post disease onset compared with patients bled later on. Doctors had used bloodletting for at least 2,000 years for a wide variety of purposes. Louis's approach was a first-step toward what we would call today an evidence-based medicine. A book denouncing "Bad Medicine" throughout history suggests that Louis inappropriately analyzed his data, overestimated the alleged benefits of venesection on the evolution of pneumonia and therefore contributed to promote this dangerous treatment. I show in this article that these criticisms are inaccurate. In particular, Louis was aware of the potential confounding effect of age and interpreted his data accordingly. Accusing Louis of "bad medicine" misses the historical importance of his struggle to improve clinical medicine using population thinking and group comparison.


Association of Computed Tomography Radiomics Signature with Progression-free Survival in Neuroblastoma Patients.
To investigate the association of computed tomography radiomics signature with progression-free survival (PFS) in neuroblastoma patients. We retrospectively included 167 neuroblastoma patients who were divided into a training set and a test set through stratified sampling at a ratio of 7:3. Regions of interest of the primary tumours were delineated on pretreatment contrast-enhanced computed tomography images and radiomics features were extracted from them. The intraclass correlation coefficient, Pearson correlation coefficient, and least absolute shrinkage and selection operator Cox regression algorithm were applied to select radiomics features and construct the radiomics signature. The effectiveness of the signature in predicting PFS was evaluated using the concordance index (C-index) and 95% confidence interval in both the training and the test sets. The time-dependent receiver operator characteristic curve of the radiomics signature was plotted and the area under the curve (AUC) was calculated. A calibration curve was used to assess the difference between the predicted probability of the radiomics signature and the observed probability at different time points. The radiomics signature was composed of six features, which achieved a C-index of 0.733 (95% confidence interval 0.664-0.803) in the training set and 0.734 (95% confidence interval 0.608-0.861) in the test set. In the training set, the radiomics signature yielded an AUC of 0.707, 0.737, 0.788, 0.859 and 0.829 for 1-, 2-, 3-, 4- and 5-year PFS, respectively. Similarly, the radiomics signature exhibited an AUC of 0.738, 0.807, 0.761, 0.787 and 0.818 for 1-, 2-, 3-, 4- and 5-year PFS, respectively, in the test set. The calibration curves showed no significant difference between the predicted probability of the radiomics signature and the observed probability for up to 5 years. Computed tomography radiomics features exhibit a significant correlation with the PFS of neuroblastoma patients, particularly in terms of long-term outcomes.


RNA interference of a putative S-adenosyl-L-homocysteine hydrolase gene affects larval performance in Leptinotarsa decemlineata (Say).
In Leptinotarsa decemlineata, juvenile hormones (JHs) play primary roles in the regulation of metamorphosis, reproduction and diapause. In JH biosynthetic pathway in insect corpora allata, methylation of farnesoic acid or JH acid using S-adenosyl-L-methionine generates a potent feedback inhibitor S-adenosyl-L-homocysteine (AdoHcy). Rapid removal of AdoHcy is hypothesized to be essential for JH synthesis. AdoHcy hydrolase (SAHase) is the only eukaryotic enzyme catalyzing the removal. In the present paper, we firstly cloned a putative LdSAHase gene from L. decemlineata. The cDNA consists of 1806 bp and encodes a 525 amino acid protein. LdSAHase was expressed in all developmental stages. The gene had the highest and the lowest level of transcription respectively in the 3rd- and 4th-instars' heads that contain corpora allata, which was positively correlated with JH titer in the haemolymph and the mRNA level of a JH early-inducible gene, the Krüppel homolog 1 gene (Kr-h1). Secondly, dietary ingestion of bacterially-expressed LdSAHase-dsRNA significantly decreased LdSAHase and LdKr-h1 mRNA levels, reduced JH titer, and caused the death of the larvae, and the failure of pupation and adult emergence. After continuous exposure for 12 days, 42% of the larvae died, 65% of the prepupae failed to pupate and 100% of the pupae failed to emerge. Moreover, RNAi-mediated LdSAHase knockdown also reduced larval developing time, and decreased larval weight. Lastly, application of JH analogue pyriproxyfen to LdSAHase-dsRNA-exposed larvae did not greatly increase LdSAHase expression level and JH content, but up-regulated LdKr-h1 mRNA level. Expectedly, pyriproxyfen application could partially rescue the negative effects on the survival and the development. Thus, our results support the hypothesis that SAHase plays a critical role in JH biosynthesis in insects.


Shear-mediated crystallization from amorphous calcium phosphate to bone apatite.
The contribution of fluid shear stress (FSS) on the conversion of amorphous calcium phosphate (ACP) to bone apatite is investigated. The ACP precursors are prepared by using a wet-chemistry method and further exposed to the constant FSS environment with values of 0.5, 1.0, 1.5, and 2.0Pa. At the designated time points, the apatites are characterized by transmission electron microscopy, X-ray diffraction, and inductively coupled plasma-mass spectroscopy. The results show that, the low FSS (≤1.0Pa) has positive effects on the transition of ACP, characterized by the accelerated crystallization velocity and the well-organized calcium-deficient hydroxyapatite (CDHA) structure, whereas the high FSS (>1.0Pa) has negative effects on this conversion process, characterized by the poor CDHA crystal morphologies and the destroyed structures. The bioactivity evaluations further reveal that, compared with the FSS-free group, the CDHA prepared under 1.0Pa FSS for 9h presents the more biocompatible features with pre-osteoblast cells. These results are helpful for understanding the mechanism of apatite deposition in natural bone tissue.


Associations of hypoglycemia, glycemic variability and risk of cardiac arrhythmias in insulin-treated patients with type 2 diabetes: a prospective, observational study.
Insulin-treated patients with type 2 diabetes (T2D) are at risk of hypoglycemia, which is associated with an increased risk of cardiovascular disease and mortality. Using a long-term monitoring approach, we investigated the association between episodes of hypoglycemia, glycemic variability and cardiac arrhythmias in a real-life setting. Insulin-treated patients with T2D (N = 21, [mean ± SD] age 66.8 ± 9.6 years, BMI 30.1 ± 4.5 kg/m2, HbA1c 6.8 ± 0.4% [51.0 ± 4.8 mmol/mol]) were included for a one-year observational study. Patients were monitored with continuous glucose monitoring ([mean ± SD] 118 ± 6 days) and an implantable cardiac monitor (ICM) during the study period. Time spend in hypoglycemia was higher during nighttime than during daytime ([median and interquartile range] 0.7% [0.7-2.7] vs. 0.4% [0.2-0.8]). The ICMs detected 724 episodes of potentially clinically significant arrhythmias in 12 (57%) participants, with atrial fibrillation and pauses accounting for 99% of the episodes. No association between hypoglycemia and cardiac arrhythmia was found during daytime. During nighttime, subject-specific hourly incidence of cardiac arrhythmias tended to increase with the occurrence of hypoglycemia (incident rate ratio [IRR] 1.70 [95% CI 0.36-8.01]) but only slightly with increasing time in hypoglycemia (IRR 1.04 [95% CI 0.89-1.22] per 5 min). Subject-specific incidence of cardiac arrhythmias during nighttime increased with increasing glycemic variability as estimated by coefficient of variation whereas it decreased during daytime (IRR 1.33 [95% CI 1.05-1.67] and IRR 0.77 [95% CI 0.59-0.99] per 5% absolute increase, respectively). Cardiac arrhythmias were common in insulin-treated patients with T2D and were associated with glycemic variability, whereas arrhythmias were not strongly associated with hypoglycemia. NCT03150030, ClinicalTrials.gov, registered May 11, 2017. https://clinicaltrials.gov/ct2/show/NCT03150030.


Evolution of robotic surgery in the treatment of localized prostate cancer.
Adenocarcinoma of the prostate is the second most common cancer in men in the United States (following only skin cancer) and accounts for 33% of all newly diagnosed male cancers. It is estimated that in 2007, 218,890 men will be diagnosed with prostate cancer and 27,050 will die from this disease. While most currently diagnosed prostate cancers are localized, radical prostatectomy remains a gold standard treatment. Since its original description, radical retropubic prostatectomy has evolved over the last three decades to a precise, sophisticated procedure with minimal mortality, and excellent surgical outcomes. However, despite its efficacy, open surgical treatment is inherently associated with blood loss and significant pain. Due to these reasons, many men have sought other, less invasive forms of treatment. With its development in the late 1990s, minimally invasive surgery has significantly and irrevocably changed the surgical treatment of prostate cancer. Robotic-assisted technology has further propelled the utilization of the laparoscopic approach for radical prostatectomy, particularly for non-laparoscopic trained surgeons. The implementation of robotic technology has been rapid. Presently, 7 years after its approval by the FDA, many hospitals have established for robotic-assisted radical prostatectomy programs. This trend will undoubtedly continue to grow as more surgeons become familiar with the procedure, more robotic systems become available, and increasingly mature data is published. Robotic-assisted laparoscopic radical prostatectomy allows patients the benefits of minimally invasive surgery with functional and oncological results comparable to those from open and standard laparoscopic procedures, we believe that this surgical approach will shortly evolve into the standard surgical approach for localized prostate cancer.


A review and comparison of common maternal positions during the second-stage of labor.
The second-stage of labor is the most stressful part of childbirth process and the proper maternal position during this period is paramount for women's safe vaginal birth. Midwives play a pivotal role in managing maternal positions during the second-stage of labor. However, there is limited evidence to support an ideal maternal position during the second-stage of labor. Further, the difference between different maternal positions might not be apparent. This paper aims to review and compare the benefits and risks of common maternal positions during the second-stage of labor, thereby to provide midwives evidence-based practical guidelines.


Intestinal infections in patients with acquired immunodeficiency syndrome. A prospective study in 132 patients.
We studied prospectively 132 patients with acquired immunodeficiency syndrome to define the spectrum of enteric pathogens during this disease, with special reference to the correlation between the lesions, the infections, and the symptoms. Forty-four percent of the patients harbored at least one enteric pathogen: the most frequently recovered were Cryptosporidium (28), cytomegalovirus (16), Entamoeba histolytica (13), Giardia lamblia (9), and Mycobacterium avium intracellulare (7). Patients harboring pathogens were more likely to be diarrheics (69%) than patients without a pathogen (38%; P = 0.01) and more likely to have endoscopic lesions (29%) than patients without a pathogen (4%; P less than 0.001). The most common pathogen associated with diarrhea was Cryptosporidium. Cytomegalovirus, Entamoeba histolytica, and Salmonella typhimurium were each significantly associated with endoscopic lesions. Patients with cytomegalovirus infection tended to have a greater incidence of ulcer than patients without cytomegalovirus infection. Stool analysis diagnosed 61% of the infections, while endoscopy diagnosed 44%. Seven percent were recognized by stool analysis and endoscopy. When considering the 24 patients in whom accurate diagnosis warranted endoscopic biopsies, stool examination alone would have given an incomplete diagnosis in 14 patients (due to the presence of polyinfection). The frequency of inaccurate diagnosis of infection by stool determination alone, plus the development of new antiviral agents that suppress cytomegalovirus, may favor the earlier application of endoscopic evaluation in these patients.


The chip manufacturing industry: Environmental impacts and eco-efficiency analysis.
Semiconductor manufacturing has followed the fate of a large part of industrial production: many companies, around the world, have maintained higher functions (design and engineering) and outsourced other production stages to third-party manufacturers, located mostly in Asia. Some chip companies have thus become "fabless" firms, commissioning the "fabrication" of their product to wafer "foundries" or "fabs". For the first time, in this paper, by calculating and subsequently analyzing various key environmental performance indicators (KEPIs) from the data of the fabs Corporate Social Responsibility (CSR) reports, the environmental impacts and the eco-efficiency of the world's leading semiconductor foundries are analyzed and assessed. The aim is to highlight the relations between company size, technological capacity and environmental impact. A preliminary homogenization was necessary to process the company original data and indicators, often related to different units of production, and to obtain raw data in absolute value. Subsequently, adopting a single common manufacturing index (MI), it was possible to obtain and use new comparable performance indicators and KEPIs. The consequent comparative assessment allowed to give a reliable overall picture of the current resource consumption and pollution of this highly strategic sector, highlighting its next heavy environmental challenges. The result, in fact, is that, differently to what happens in many other sectors, in the semiconductor industry, larger company size (higher revenue), higher value added per wafer produced (higher revenue/MI), and higher technological capacity (higher R&D expenses and smaller technology node) are not always related to lower quantities (per unit of production) of water, energy, waste, wastewater and GHG emissions. It is hoped that, for the future, foundry firms, especially those with the most advanced technologies, will invest much more to optimize their resource use and to further reduce GHGs emissions and waste generation.


Lymphoid cells of BB/W diabetic rats are cytotoxic to islet beta cells in vitro.
Assays were developed to detect cell-mediated immune destruction of pancreatic islet beta cells by lymphoid cells isolated from diabetic BioBreeding/Worcester (BB/W) rats. Splenic lymphoid cells from diabetic (D), diabetes-prone (DP), and diabetes-resistant (DR) BB/W rats were incubated for 2 days with monolayer cultures of major histocompatibility complex (MHC)-compatible Wistar-Furth (WF) rat islet cells or a rat islet cell line (RIN), and islet beta cell survival was determined by measuring insulin content in the cultures. D splenic lymphoid cells significantly decreased insulin content in WF rat islet (-32%) and RIN cultures (-77%). DP cells also significantly reduced the insulin content in WF rat islet (-20%) and RIN cultures (-63%), whereas DR cells had no significant effect. Islet-directed cytotoxicity was detected also by the release of 51Cr from RIN cells incubated for 8 h with BB/W spleen cells. Cytotoxicity was linearly related to the number of effector spleen cells. At a target: effector of 1:20, lysis (mean +/- SEM) of RIN target cells by spleen cells from D rats (21.6 +/- 2.0%) and DP rats (16.5 +/- 4.1%) was significantly greater than the effect of DR spleen cells (5.4 +/- 1.0%). D and DP splenic lymphoid cells activated in vitro for 2 days with concanavalin A exhibited a doubling of cytotoxicity to RIN islet cells. These results provide direct evidence for lymphoid cell-mediated immune damage to islet beta cells in diabetic BB rats.


Association Between Blunted Glomerular Hyperfiltration in Pregnancy and Severe Maternal Morbidity-A Research Letter.
Glomerular hyperfiltration is one physiological adaptation to pregnancy, marked by a decline in serum creatinine (SCr) concentration by 16 weeks' gestation. It is not known whether blunted glomerular hyperfiltration leads to adverse maternal outcomes, including severe maternal morbidity (SMM). To evaluate the association between blunted glomerular hyperfiltration and subsequent SMM or death. Population-based cohort study. Ontario, Canada, from 2008 to 2019. Included were births among women who had ≥ 1 SCr measured as an outpatient within 10 weeks before conception ("preconception"), and again, at 110/7 to 206/7 weeks' gestation ("in-pregnancy"). Excluded were women who died before birth, who had end-stage renal disease or kidney transplantation before conception, or whose pre-pregnancy SCr was 125 μmol/L. Net glomerular hyperfiltration defined as the preconception minus the in-pregnancy SCr. The primary study outcome was SMM or death arising from 23 weeks' gestation up to 42 days after the index birth. Adjusted relative risks (aRRs) were calculated using Modified Poisson regression per 1-SD net blunting of glomerular hyperfiltration adjusting for important covariates. A total of 10,323 births met all inclusion criteria. The mean (SD) SCr was 61.7 (11.0) μmol/L preconception, 48.0 (9.2) μmol/L in-pregnancy, and the mean net difference 13.6 (8.2) μmol/L. Among these births, the adjusted RR of SMM or death from 23 weeks' gestation up to 42 days post-partum was 1.16 (95% confidence interval 1.14-1.30) per 1-SD (8.2 μmol/L) net blunting of glomerular hyperfiltration. As SCr assessment is not a routine part of pregnancy care, its measurement could have been for a specific health condition thereby imparting selection bias. Blunted glomerular hyperfiltration in pregnancy may identify some women at higher risk of SMM. Further prospective research is needed about the implications of glomerular hyperfiltration in early pregnancy.


Interations of gonadotropins with corpus luteum membranes. VII. Association of hCG-binding and adenylate cyclase activities with rabbit corpus luteum plasma-membranes.
Previous studies with rat luteal cell plasma membranes indicated a dissociation of hCG binding sites and adenylate cyclase activity. The hormone binding sites were associated with a light membrane (d 1.13) fraction derived from the microvillous surface while the cyclase enzyme was associated with a heavy membrane (d 1.17) fraction derived from the basolateral surface of the cell. In this study of plasma membranes from 8-day pseudopregnant rabbit corpora lutea both hCG binding and adenylate cyclase activity were associated with a light membrane (d 1.13) fraction. No heavy membrane material was detected.


Epoxide hydrolase activity in isolated peroxisomes of mouse liver.
Using trans-stilbene oxide as substrate, the subcellular distribution of epoxide hydrolase was investigated in livers from DBA/2 mice. The highest specific activities were found in cytosolic and light mitochondrial fractions. Isopycnic subfractionation of the light mitochondrial fraction showed that the organelle-bound trans-stilbene oxide hydrolase is localized in peroxisomes.


Haplotypes in the gene encoding protein kinase c-beta (PRKCB1) on chromosome 16 are associated with autism.
Autism is a developmental disorder characterized by impairments in social interaction and communication associated with repetitive patterns of interest or behavior. Autism is highly influenced by genetic factors. Genome-wide linkage and candidate gene association approaches have been used to try and identify autism genes. A few loci have repeatedly been reported linked to autism. Several groups reported evidence for linkage to a region on chromosome 16p. We have applied a direct physical identity-by-descent (IBD) mapping approach to perform a high-density (0.85 megabases) genome-wide linkage scan in 116 families from the AGRE collection. Our results confirm linkage to a region on chromosome 16p with autism. High-resolution single-nucleotide polymorphism (SNP) genotyping and analysis of this region show that haplotypes in the protein kinase c-beta gene are strongly associated with autism. An independent replication of the association in a second set of 167 trio families with autism confirmed our initial findings. Overall, our data provide evidence that the PRKCB1 gene on chromosome 16p may be involved in the etiology of autism.


Well-conditioned model predictive control.
Model-based predictive control is an advanced control strategy that uses a move suppression factor or constrained optimization methods for achieving satisfactory closed-loop dynamic responses of complex systems. While these approaches are suitable for many processes, they are formulated on the selection of certain parameters that are ambiguous and also computationally demanding which makes them less suited for tight control of fast processes. In this paper, a new dynamic matrix control (DMC) algorithm is proposed that reduces inherent ill-conditioning by allowing the process prediction time step to exceed the control time step. The main feature, that stands in contrast with current DMC approaches, is that the original open-loop data are used to evaluate a "shifting factor" m in the controller matrix where m replaces the move suppression coefficient. The new control algorithm is practically demonstrated on a fast reacting process with better control being realized in comparison with DMC using move suppression. The algorithm also gives improved closed-loop responses for control simulations on a multivariable nonlinear process having variable dead-time, and on other models found in the literature. The shifting factor m is generic and can be effectively applied for any control horizon.


Analysis of risk factors for the development of gallstones after gastrectomy.
The incidence of gallstones is higher in people who have undergone gastrectomy than in the general population, but the cause of this is unknown. Between January 1992 and January 2003, 749 patients underwent ultrasonography of the gallbladder after gastrectomy for gastric cancer. A total of 2327 examinations were carried out. The incidence of gallstones was compared in subgroups of patients classified according to the type of reconstruction, extent of gastrectomy, whether the duodenum was excluded and type of lymph node dissection. The incidence of gallstones was significantly higher after total compared with partial gastrectomy (27.9 versus 7.8 per cent at 5 years; P < 0.001). Reconstruction with duodenal exclusion was associated with a significantly higher incidence than non-exclusion (25.1 versus 8.2 per cent at 5 years; P < 0.001). Patients who had lymph node dissection in the hepatoduodenal ligament had a significantly higher incidence of gallstones than those who did not (28.2 versus 7.5 per cent at 5 years; P < 0.001). In multivariate analysis that included type of reconstruction and lymph node dissection, lymph node dissection in the hepatoduodenal ligament was identified as the most significant risk factor for gallstone development (odds ratio 3.66 (95 per cent confidence interval 2.16 to 6.22); P < 0.001). Lymph node dissection in the hepatoduodenal ligament, total gastrectomy and exclusion of the duodenum are risk factors for gallstones after gastrectomy.


Combined mitral and aortic valve stenosis caused by two different etiologies, rheumatic and congenital.
Described herein are five patients who had double left-sided cardiac valve replacement for mitral and aortic valve stenosis resulting from two different etiologies: rheumatic heart disease, the cause of the mitral stenosis, and congenital heart disease (bicuspid valve), the underlying cause of the aortic stenosis.


Excimer laser keratectomy for correction of astigmatism.
We treated 13 eyes (12 patients) with excimer laser surgery for correction of astigmatism using linear corneal T-excisions. All eyes were followed up for a minimum of three months. We used a newly developed delivery system and special contact masks to deliver the 193-nm excimer light. Astigmatic corrections of up to 4.16 diopters were obtained. The actual corrections corresponded well with the intended values as predicted by a biomechanical theory. The refractive change over time was different than that observed after knife incisions, suggesting different repair mechanisms. An epithelial plug filling the whole T-excision persisted for over one year in all eyes.


Genetic variation at innate and adaptive immune genes - contrasting patterns of differentiation and local adaptation in a wild gull.
Immunogenetic variation in natural vertebrate populations is expected to respond to spatial and temporal fluctuations in pathogen assemblages. While spatial heterogeneity in pathogen-driven selection enhances local immunogenetic adaptations and population divergence, different immune genes may yield contrasting responses to the environment. Here, we investigated population differentiation at the key pathogen recognition genes of the innate and adaptive immune system in a colonial bird species, the black-headed gull Chroicocephalus ridibundus. We assessed genetic variation at three toll-like receptor (TLR) genes (innate immunity) and the major histocompatibility complex (MHC) class I and II genes (adaptive immunity) in gulls from seven colonies scattered across Poland. As expected, we found much greater polymorphism at the MHC than TLRs. Population differentiation at the MHC class II, but not MHC-I, was significantly stronger than at neutral microsatellite loci, suggesting local adaptation. This could reflect spatial variation in the composition of extracellular parasite communities (e.g., helminths), possibly driven by sharp differences in habitat structure between colonies. Despite contrasting patterns of population differentiation, both MHC classes showed similar regimes of diversifying selection. Some significant population differentiation was also observed at TLRs, suggesting that innate immune receptors may respond to fine-scale spatial variation in pathogen pressure, although this pattern could have been enhanced by drift. Our results suggested that local adaptation at the pathogen recognition immune genes can be maintained at relatively small or moderate spatial scales in species with high dispersal potential and they highlighted the complexity of immunogenetic responses of animals to heterogeneous environments.


Further identification of NSF* as an epilepsy related gene.
Previous data proved that NSF* was an epilepsy related gene (ERG1). In this study, using phosphorothioate oligodeoxynucleotide (PS-ODN), an antisense of NSF to downregulate the function of NSF in vitro cultured hippocampus neurons and PC12, this treatment simultaneously induced enhancement of the neurite outgrowth of hippocampal neurons and PC12, a phenomenon similar to the structural changes following epilepsy. Immunocytochemistry analysis showed that the enhancement of neurite outgrowth was in a sequence-specific manner and Northern blot confirmed that the decrease of NSF mRNA levels in PC12 was in a dose-dependent manner. Moreover the expression of NSF was downregulated during differentiation of PC12 induced by NGF and high KCl. Therefore, providing more evidence to support the fact that NSF was an ERG1.


Treatment of spastic dysphonia by EMG biofedback.
Two middle-aged subjects, a male and female, with spastic dysphonia (hoarseness, stammering) were treated with both frontalis and throat muscle electromyographic (EMG) biofeedback. Both subjects reported no noticeable improvement in their voice qualities. Results of a battery of psychological tests provided some insight into the inability of EMG treatment, as well as other therapeutic approaches, to alleviate the pathology.


Determinants of childhood tuberculosis--a case control study among children registered under revised National Tuberculosis Control Programme in a district of South India.
To study the determinants of Tuberculosis (TB) in children between the age group of 0-14 years receiving treatment under Revised National TB Control Programme (RNTCP). A case (registered under RNTCP) control study was undertaken with 41 cases and 82 controls. Factors found to have significance according to binary logistic regression were low-birth weight (LBW) [Odd's ratio = 3.56],Malnutrition [Odd's ratio = 3.96], Passive smoking [Odd's ratio=6.28] and exposure to fire-wood smoke [Odd's ratio = 6.91]. LBW, malnutrition, passive smoking and fire-wood smoke are the risk factors to be addressed to prevent pediatric TB.


Theobromine suppresses adipogenesis through enhancement of CCAAT-enhancer-binding protein β degradation by adenosine receptor A1.
Theobromine, a methylxanthine derived from cacao beans, reportedly has various health-promoting properties but molecular mechanism by which effects of theobromine on adipocyte differentiation and adipogenesis remains unclear. In this study, we aimed to clarify the molecular mechanisms of the anti-adipogenic effect of theobromine in vitro and in vivo. ICR mice (4week-old) were administered with theobromine (0.1g/kg) for 7days. Theobromine administration attenuated gains in body and epididymal adipose tissue weights in mice and suppressed expression of adipogenic-associated genes in mouse adipose tissue. In 3T3-L1 preadipocytes, theobromine caused degradation of C/EBPβ protein by the ubiquitin-proteasome pathway. Pull down assay showed that theobromine selectively interacts with adenosine receptor A1 (AR1), and AR1 knockdown inhibited theobromine-induced C/EBPβ degradation. Theobromine increased sumoylation of C/EBPβ at Lys133. Expression of the small ubiquitin-like modifier (SUMO)-specific protease 2 (SENP2) gene, coding for a desumoylation enzyme, was suppressed by theobromine. In vivo knockdown studies showed that AR1 knockdown in mice attenuated the anti-adipogenic effects of theobromine in younger mice. Theobromine suppresses adipocyte differentiation and induced C/EBPβ degradation by increasing its sumoylation. Furthermore, the inhibition of AR1 signaling is important for theobromine-induced C/EBPβ degradation.


Changes in Ambulatory Blood Pressure Phenotype over Time in Children and Adolescents with Elevated Blood Pressures.
To determine the stability of ambulatory blood pressure monitoring (ABPM) over time in children referred for evaluation of elevated BPs and assess for factors predicting change. This retrospective chart review conducted at Seattle Children's Hospital and University of Pittsburgh Medical Center Children's Hospital of Pittsburgh identified 124 children referred for elevated BPs with 2 ABPM studies at least 6 months apart. All subjects received lifestyle counseling. Subjects with secondary hypertension (HTN) or on antihypertensive medication were excluded. ABPM phenotype was classified using American Heart Association guidelines as showing normal BP, prehypertension, and HTN. Generalized linear mixed effect regression models were used to regress stable, improving, or worsening HTN outcomes at study follow-up on baseline BP index and load variables. The median age of patients was 14.1 years (73% males) and the median interval between studies was 18 months. ABPM phenotype changed in 58 of 124 children, with 16% worsening and 31% improving. Older age was associated with persistence of HTN. Although not significant, decrease in body mass index z-score tracked with sustained normal ambulatory BPs. Although the sample size is small, our study suggests ABPM phenotype shows variability over time. Further study is required to identify factors supporting risk for progression of ABPM phenotype over time.


Reverse total shoulder arhroplasty for the treatment of failed fixation in proximal humeral fractures.
This study evaluates the clinical outcomes in patients with proximal humerus fractures (PHF) treated with reverse total shoulder arthroplasty (RTSA) as a revision procedure for failed fixation that have more than 5 years of follow-up. This is a retrospective study of 270 RTSA. The inclusion criteria for this study consisted of patients initially treated with either open reduction and plate fixation (ORIF) or fixation using an intramedullary nail (IMN), who were managed with a single-stage revision to a RTSA, and had a minimum of 24 months clinical and radiological follow-up. Six patients with failed fixation of displaced PHF were revised with RTSA. One patient was excluded from the study because she died. Five shoulders were reviewed for the purpose of this study. The patients were evaluated using Constant score, relative Constant score and visual analogue scale for pain. The mean follow-up was 89 months (65-108). The mean absolute Constant score improved from 31, 81 to 44, 2 and the relative Constant score improved from 31,81% to 67,2%. Mean VAS improved from 6, 8 to 2. One patient rated their outcome excellent, 1good, 1 satisfied and 2 poor. RTSA is an appropriate treatment as a revision surgery for failed fixation of PHF. Patients should be adequately warned that they will improve their function but may have complications following this salvage procedure.


Contrast-enhanced ultrasonography: usefulness in the assessment of postoperative recurrence of Crohn's disease.
The aim of this study was to assess whether the contrast-enhanced ultrasonography (CEUS) can increase the value of the ultrasonography in the study of postoperative recurrence of Crohn's disease (CD). 60 patients with CD who had previously undergone ileocolic resection underwent prospectively both CEUS and colonoscopy within a 3-day period. The sonographic examination included evaluation of bowel wall thickness, transmural complications, colour Doppler grade and contrast-enhanced US. In addition a sonographic score was established. The capacity of CEUS to diagnose endoscopic recurrence, as well as its severity, was assessed by calculating the sensitivity, specificity and positive and negative predictive values, accuracy and odds ratio, with their respective 95% confidence intervals. The areas under the receiver operating characteristic (ROC) curves were also calculated. 49 out of 60 patients showed endoscopic postoperative recurrence. Severe endoscopic recurrence was present in 34 patients (57%). Classic ultrasound parameters (wall thickness >3mm and colour Doppler flow) revealed an accuracy of 88.3% for the diagnosis of recurrence. Sonographic score 2, including thickness >5mm or contrast enhancement >46%, improved the results with a sensitivity, specificity and accuracy of 98%, 100% and 98.3%, respectively, in the diagnosis of endoscopic recurrence. The area under the ROC curve was 0.99, in remarkable agreement with endoscopy (k: 0.946). Sonographic score 3, including thickness >5mm, contrast enhancement >70% or fistula identified 32 out of 34 (94.1%) severe endoscopic recurrences. The area under the ROC curve was 0.836, in good agreement with endoscopy (k: 0.688). CEUS shows excellent sensitivity and specificity for the diagnosis of postoperative recurrence in CD and can also detect severe recurrences.


Syntenic block overlap multiplicities with a panel of reference genomes provide a signature of ancient polyploidization events.
Following whole genome duplication (WGD), there is a compact distribution of gene similarities within the genome reflecting duplicate pairs of all the genes in the genome. With time, the distribution broadens and loses volume due to variable decay of duplicate gene similarity and to the process of duplicate gene loss. If there are two WGD, the older one becomes so reduced and broad that it merges with the tail of the distributions resulting from more recent events, and it becomes difficult to distinguish them. The goal of this paper is to advance statistical methods of identifying, or at least counting, the WGD events in the lineage of a given genome. For a set of 15 angiosperm genomes, we analyze all 15 × 14 = 210 ordered pairs of target genome versus reference genome, using SynMap to find syntenic blocks. We consider all sets of B ≥ 2 syntenic blocks in the target genome that overlap in the reference genome as evidence of WGD activity in the target, whether it be one event or several. We hypothesize that in fitting an exponential function to the tail of the empirical distribution f (B) of block multiplicities, the size of the exponent will reflect the amount of WGD in the history of the target genome. By amalgamating the results from all reference genomes, a range of values of SynMap parameters, and alternative cutoff points for the tail, we find a clear pattern whereby multiple-WGD core eudicots have the smallest (negative) exponents, followed by core eudicots with only the single "γ" triplication in their history, followed by a non-core eudicot with a single WGD, followed by the monocots, with a basal angiosperm, the WGD-free Amborella having the largest exponent. The hypothesis that the exponent of the fit to the tail of the multiplicity distribution is a signature of the amount of WGD is verified, but there is also a clear complicating factor in the monocot clade, where a history of multiple WGD is not reflected in a small exponent.


Prevalence of trachoma in four marakez of Elmenia and Bani Suef Governorates, Egypt.
In 2015, to determine where interventions are needed to eliminate trachoma as a public health problem from Egypt, we initiated population-based prevalence surveys using the Global Trachoma Mapping Project platform in four suspected-endemic marakez (districts; singular: markaz) of the governorates of Elmenia and Bani Suef. In each markaz, 30 households were selected in each of 25 villages. Certified graders examined a total of 3682 children aged 1-9 years in 2993 households, noting the presence or absence of trachomatous inflammation-follicular (TF) and trachomatous inflammation-intense (TI) in each eye. A total of 5582 adults aged ≥15 years living in the same households were examined for trachomatous trichiasis (TT). Household-level access to water and sanitation was recorded. Three of four marakez had age-adjusted TF prevalence estimates in 1-9-year olds of >10%; the other markaz had a TF prevalence estimate of 5-9.9%. Estimates of the age- and gender-adjusted prevalence of unmanaged TT in adults ranged from 0.7% to 2.3%. Household-level access to water and sanitation was high. (We did not, however, measure use of water or sanitation facilities.) Conclusions: Each of the four marakez surveyed has trachoma as a public health problem, with a need for implementation of the SAFE (surgery, antibiotics, facial cleanliness, environmental improvement) strategy. Further mapping is also required to determine the need for interventions in other areas of Egypt.


Antidepressant-like properties of novel HDAC6-selective inhibitors with improved brain bioavailability.
HDAC inhibitors have been reported to produce antidepressant and pro-cognitive effects in animal models, however, poor brain bioavailability or lack of isoform selectivity of current probes has limited our understanding of their mode of action. We report the characterization of novel pyrimidine hydroxyl amide small molecule inhibitors of HDAC6, brain bioavailable upon systemic administration. We show that two compounds in this family, ACY-738 and ACY-775, inhibit HDAC6 with low nanomolar potency and a selectivity of 60- to 1500-fold over class I HDACs. In contrast to tubastatin A, a reference HDAC6 inhibitor with similar potency and peripheral activity, but more limited brain bioavailability, ACY-738 and ACY-775 induce dramatic increases in α-tubulin acetylation in brain and stimulate mouse exploratory behaviors in novel, but not familiar environments. Interestingly, despite a lack of detectable effect on histone acetylation, we show that ACY-738 and ACY-775 share the antidepressant-like properties of other HDAC inhibitors, such as SAHA and MS-275, in the tail suspension test and social defeat paradigm. These effects of ACY-738 and ACY-775 are directly attributable to the inhibition of HDAC6 expressed centrally, as they are fully abrogated in mice with a neural-specific loss of function of HDAC6. Furthermore, administered in combination, a behaviorally inactive dose of ACY-738 markedly potentiates the anti-immobility activity of a subactive dose of the selective serotonin reuptake inhibitor citalopram. Our results validate new isoform-selective probes for in vivo pharmacological studies of HDAC6 in the CNS and reinforce the viability of this HDAC isoform as a potential target for antidepressant development.


Ecomorphological diversification of some barbs and carps (Cyprininae, Cyprinidae) in the Lower Mekong Basin of Thailand.
Morphological variation is fundamentally related to various aspects of fish ecology, including foraging, locomotion, and habitat utilisation. Twenty-six species of closely related cyprinid fish (n = 502) were analysed for patterns of morphological variations by using geometric morphometric methods. Ecological data of feeding and habitat preferences were determined by the observations in fields and laboratory together with the gathering of bibliographic information. The findings of major variation displayed in all parts of the fish body and correlated with ecological parameters. Variations of head shape especially form and position of mouthpart involved with feeding behaviours, whereas the variations of body depth and length which affected swimming patterns reflected responsiveness of water currents and habitat uses. Adaptation of head shape and body elongation was remarkably related to the feeding regime, swimming manoeuvrability and habitat utilisation of the species. Some convergent variation was observed between the tribes Smiliogastrini and Poropuntiini. Therefore, we propose that the morphological diversity of cyprinine fish is mainly affected by ecological gradients, while phylogenetic effects on morphology are minor.


DNA-capped mesoporous silica nanoparticles as an ion-responsive release system to determine the presence of mercury in aqueous solutions.
We have developed DNA-functionalized silica nanoparticles for the rapid, sensitive, and selective detection of mercuric ion (Hg(2+)) in aqueous solution. Two DNA strands were designed to cap the pore of dye-trapped silica nanoparticles. In the presence of ppb level Hg(2+), the two DNA strands are dehybridized to uncap the pore, releasing the dye cargo with detectable enhancements of fluorescence signal. This method enables rapid (less than 20 min) and sensitive (limit of detection, LOD, 4 ppb) detection, and it was also able to discriminate Hg(2+) from twelve other environmentally relevant metal ions. The superior properties of the as-designed DNA-functionalized silica nanoparticles can be attributed to the large loading capacity and highly ordered pore structure of mesoporous silica nanoparticles, as well as the selective binding of thymine-rich DNA with Hg(2+) . Our design serves as a new prototype for metal-ion sensing systems, and it also has promising potential for detection of various targets in stimulus-release systems.


Validation of X-ray Crystal Structure Ensemble Representations of SARS-CoV-2 Main Protease by Solution NMR Residual Dipolar Couplings.
Considerable debate has focused on whether sampling of molecular dynamics trajectories restrained by crystallographic data can be used to develop realistic ensemble models for proteins in their natural, solution state. For the SARS-CoV-2 main protease, Mpro, we evaluated agreement between solution residual dipolar couplings (RDCs) and various recently reported multi-conformer and dynamic-ensemble crystallographic models. Although Phenix-derived ensemble models showed only small improvements in crystallographic Rfree, substantially improved RDC agreement over fits to a conventionally refined 1.2-Å X-ray structure was observed, in particular for residues with above average disorder in the ensemble. For a set of six lower resolution (1.55-2.19 Å) Mpro X-ray ensembles, obtained at temperatures ranging from 100 to 310 K, no significant improvement over conventional two-conformer representations was found. At the residue level, large differences in motions were observed among these ensembles, suggesting high uncertainties in the X-ray derived dynamics. Indeed, combining the six ensembles from the temperature series with the two 1.2-Å X-ray ensembles into a single 381-member "super ensemble" averaged these uncertainties and substantially improved agreement with RDCs. However, all ensembles showed excursions that were too large for the most dynamic fraction of residues. Our results suggest that further improvements to X-ray ensemble refinement are feasible, and that RDCs provide a sensitive benchmark in such endeavors. Remarkably, a weighted ensemble of 350 PDB Mpro X-ray structures provided slightly better cross-validated agreement with RDCs than any individual ensemble refinement, implying that differences in lattice confinement also limit the fit of RDCs to X-ray coordinates.


MicroRNA-132 inhibits cell growth and metastasis in osteosarcoma cell lines possibly by targeting Sox4.
Increasing evidence has confirmed that dysregulation of microRNAs (miRNAs) can contribute to the progression and metastasis of human tumors. Previous studies have shown that dysregulation of microRNAs (miRNAs) can contribute to the progression and metastasis of human tumors. However, the precise mechanisms of miR‑132 in osteosarcoma have not been well clarified. Real-time PCR was performed to detect the expression of miR‑132 in osteosarcoma cell lines. miR-132 mimic, miR‑132 inhibitor and negative control were transfected into osteosarcoma cells and the effects of miR‑132 on the cell growth and metastasis were investigated. Furthermore, protein level of Sox4 was measured by western blotting. Luciferase assays were performed to validate Sox4 as miR‑132 target in osteosarcoma cells. We found that miR‑132 was downregulated in osteosarcoma cell lines. Introduction of miR‑132 significantly inhibited proliferation, arrested cell cycle and induced apoptosis in osteosarcoma cells. Besides, invasion and epithelial-mesenchymal transition (EMT) of osteosarcoma cells was suppressed by overexpressing miR‑132. However, downregulation of miR‑132 promoted cell growth and metastasis in osteosarcoma cells. Bioinformatics analysis predicted that Sox4 was a potential target gene of miR‑132. Luciferase reporter assay demonstrated that miR‑132 could directly target Sox4. Moreover, the low level of miR‑132 was associated with increased expression of Sox4 in osteosarcoma cells. Sox4 inhibition suppressed cell malignant behaviors. Overexpression of Sox4 in osteosarcoma cells transfected with miR‑132 mimic partially reversed the inhibitory effect of miR‑132. In conclusion, miR‑132 inhibited cell growth and metastasis in osteosarcoma cells by downregulation of Sox4, and knockdown of Sox4 was essential for the miR-132-inhibited cell growth and metastasis in osteosarcoma cells.


Relationship between the Levels of mRNA Expression for Protein Phosphatase 1B and Proteins Involved in Cytoskeleton Remodeling in Squamous Cell Carcinoma of the Larynx and Hypopharynx.
We analyzed the expression of genes encoding proteins involved in cytoskeleton remodeling (RND3, SNAI1, vimentin, cofilin, adenylate cyclase-associated protein 1, ezrin, and profilin) depending on the level of expression of protein phosphatase 1B (PPM1B) mRNA on the example of squamous cell carcinoma of the larynx and hypopharynx. Against the background of a high level of PPM1B expression, a significantly high level of profilin expression was noted. Metastasis correlated with the level of snai1 expression, while relapse after combination treatment was negatively associated with the level of vimentin expression. The obtained new data can reflect molecular peculiarities of the tumor growth in squamous cell carcinoma of the larynx and hypopharynx.


Fabrication and characterization of double (W1/O/W2) emulsions loaded with bioactive peptide/polysaccharide complexes in the internal water (W1) phase for controllable release of bioactive peptide.
The objective of this study was to develop food-grade double emulsions containing bioactive peptide (BP)/polysaccharide (P) complexes and to investigate their thermal stability (e.g., BP release) at different temperatures. The BP/P complexes were formed via electrostatic interactions, and successfully encapsulated into the internal water phase of double emulsions with different oil phases. All emulsions clearly showed temperature dependence during storage. BP/P complex-loaded double emulsions showed higher thermal stability and lower release of encapsulated BP (45 °C: < 1%, 65 °C: < 30%) over time, which effectively prevented BP release within the emulsion system. For the effect of the oil phase, the BP released from double emulsions was in the order of MCT > coconut > canola oil. Thus, we concluded that BP release can be controlled in double emulsions by differently charged polysaccharides and oil types and that BP/P-loaded double emulsions can be utilized as functional ingredients for developing heat-sensitive food products.


[Digital filtering of acoustical evoked potentials].
For better analysis of ERA-potentials it is necessary to eliminate disturbing frequencies by a smoothing filter. For this we propose a special optimized digital filter, which is applicable without falsification of form and amplitude of potentials. Its efficiency will be compared with other smoothing techniques.


Spatiotemporal behaviors of the ridership of a public transportation system during an epidemic outbreak: case of MERS in Seoul.
During May and June 2015, an outbreak of the Middle East respiratory syndrome (MERS) occurred in Korea, which raised the fear of contagion throughout society and suppressed the use of public transportation systems. Exploring daily ridership data of the Seoul bus transportation system, along with the number of infected patients and search volume in web portals, we observe that ridership decreased abruptly while attention was heavily focused online. Then this temporal reduction recovered exponentially with a characteristic time of 3 weeks when newly confirmed cases began to decrease. We also find with the data of ranked keywords of web portals that areas with severely reduced ridership tended to cluster and spatiotemporal variations of such clusters were highly associated with general hospitals where MERS patients were treated. On the other hand, the spatial reduction in ridership relaxed algebraically with the distance from a general hospital while the outbreak was severe. We further probe the influence of the epidemic outbreak in the framework of linear response theory, which relates the responses to the epidemic outbreak ("perturbation") with correlations in the absence of the perturbation. Indeed, the spatial correlation function of the ridership changes is observed to follow a power law, sharing the same exponent as the spatial relaxation of the response function. This new theoretical approach offers a useful tool for understanding responses of public transportation system to epidemic or accidental disasters.


Novel therapies for children with severe asthma.
Novel therapies, such as a heliox gaseous mixture and noninvasive bilevel positive pressure ventilation, are being utilized in the treatment of the patient with severe asthma who is unresponsive to conventional medical management. Aggressive treatment may prevent intubation and its untoward complications. Both heliox and bilevel positive pressure ventilation have demonstrated clinical improvement in studies of patients refractory to standard care, both in adults and children. The studies in children are limited but show promise, especially when these therapies are used early in the treatment course and in certain subsets of patients.


Liver transplantation for protoporphyria. Evidence for the predominant role of the erythropoietic tissue in protoporphyrin overproduction.
Protoporphyria is an inherited disorder of heme biosynthesis characterized by an overproduction of protoporphyrin in the erythropoietic and hepatic tissues, the relative contribution of which in the metabolic disorder has not been directly quantitated. Excess protoporphyrin is eliminated solely by the liver into the bile and feces. We describe the case of a patient with protoporphyria complicated by severe cirrhosis in whom liver transplantation was performed and resulted in almost complete disappearance of skin photosensitivity manifestations and reduction in the level of protoporphyrin in erythrocytes. However, the level of protoporphyrin in feces was not markedly different before and after liver transplantation, which suggests that overproduction of protoporphyrin was unchanged. These findings are consistent with the view that the diseased liver and ensuing low hepatic clearance of protoporphyrin contributed to accumulation of protoporphyrin in the body and that, at least in this patient, the role of the hepatic tissue in the overproduction of protoporphyrin was small in comparison with that of the erythropoietic tissue.


Antimicrobial, anti-adhesion, anti-biofilm properties of goji berry (Lycium barbarum) against periodontal bacteria: potential benefits for periodontal diseases.
Lycium barbarum, commonly known as goji berry, Himalayan berry, or Tibetian berry, is emerging as a popular "superfood" with anti-inflammatory and antioxidant properties. However, its use for the management of oral inflammatory diseases has not been explored. The present study aims to evaluate the antimicrobial, anti-adhesion, anti-biofilm, and cytotoxic properties of an ethanolic extract of L. barbarum (LBE) against common oral and periodontal pathogens. The antimicrobial properties of LBE against five potential periodontal pathogens (Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Prevotella intermedia, Tanerella forsythia) were tested and compared to chlorhexidine and doxycycline using serial dilution and disc diffusion assay. The MTT Assay was performed for evaluating the cytotoxicity and cell viability of the LBE on the gingival fibroblast and modified keratinocyte cell lines. The anti-adhesion and anti-biofilm properties of LBE against P. gingivalis at its minimal bactericidal value were also assessed. LBE inhibited the growth of periodontal pathogens as compared to control, however, the zone of inhibition of LBE was less when compared to doxycycline and chlorhexidine. The de novo extract showed a maximum zone of inhibition against Tf and Aa. The LBE extract was also compatible to gingival fibroblast tissues and oral keratinocytes at 1 mg/mL. L. barbarum is a promising alternative to Chlorhexidine for the management of oral and periodontal infections.


Neuropharmacological profile of Eclipta alba (Linn.) Hassk.
The present study deals with the investigation of standardized and phytochemically evaluated aqueous and hydroalcoholic extracts of the plant Eclipta alba for sedative, muscle-relaxant, anxiolytic, nootropic and anti-stress activities. The hydrolyzed fraction of the aqueous extract was also subjected to similar studies in rats. The aqueous and hydroalcoholic extracts were administered in a dose of 150 and 300 mg/kg, p.o., while the hydrolyzed fraction was administered in a dose of 30 mg/kg, p.o. The findings indicated nootropic activity of the aqueous extract (300 mg/kg, p.o.) and its hydrolyzed fraction (30 mg/kg, p.o.). The effect of the extracts on stress-induced alterations was evaluated. The aqueous extract and the hydrolyzed fraction provided protection against cold restraint induced gastric ulcer formation and also normalized the white blood cell count in the milk induced leukocytosis challenge model. The hydroalcoholic extract on the other hand demonstrated a significant effect only in the milk induced leukocytosis challenge model. The results point towards the potential neuropharmacological activity of the plant Eclipta alba as a nootropic and also having the property of attenuating stress induced alterations. Further neurochemical investigations can unravel the mechanism of action of the plant drug with respect to nootropic activity and help to establish the plant in the armamentarium of nootropic agents.