Small RNAs in regulating temperature stress response in plants.
Due to global climate change, temperature stress has become one of the primary causes of crop losses worldwide. Much progress has been made in unraveling the complex stress response mechanisms in plants, particularly in the identification of temperature stress responsive protein-coding genes. Recently discovered microRNAs (miRNAs) and endogenous small-interfering RNAs (siRN As) have also been demonstrated as important players in plant temperature stress response. Using high-throughput sequencing, many small RNAs, especially miRNAs, have been identified to be triggered by cold or heat. Subsequently, several studies have shown an important functional role for these small RNAs in cold or heat tolerance. These findings greatly broaden our understanding of endogenous small RNAs in plant stress response control. Here, we highlight new findings regarding the roles of miRNAs and siRNAs in plant temperature stress response and acclimation. We also review the current understanding of the regulatory mechanisms of small RNAs in temperature stress response, and explore the outlook for the use of these small RNAs in molecular breeding for improvement of temperature stress tolerance in plants.


Homocysteine and methylmalonic acid concentrations in cerebrospinal fluid: relation with age and Alzheimer's disease.
Homocysteine may be involved in the pathogenesis of late onset Alzheimer's disease. It is implicated in the metabolism of several important pathways in the brain. Methylmalonic acid (MMA) is related to the metabolism of branched chained amino acids and fatty acids. To compare cerebrospinal fluid (CSF) total homocysteine and MMA in elderly subjects, patients with Alzheimer's disease, and younger healthy controls. CSF samples were obtained from 33 patients under 20 years of age; 28 patients aged 21 to 60 years; 22 normal elderly subjects aged over 60; and 38 Alzheimer patients aged over 60. CSF total homocysteine increased with age (mean (SD): 57 (35) nmol/l in the youngest group v 123 (89) nmol/l in the elderly group (p<0.001)). There was no difference between the elderly group and Alzheimer patients (115 (62) nmol/l). CSF MMA did not differ in the elderly group and the Alzheimer group (38 (13) v 35 (14) ng/ml). In the youngest group, it was significantly higher (60 (15) ng/ml). CSF total homocysteine is not increased in Alzheimer's disease compared with age matched controls. CSF total homocysteine was correlated with age. The decrease in CSF MMA levels with age eliminates a lack of vitamin B-12 at neuronal level.


Multiple binding of antibodies to antigens: effect on radioimmunoassay binding curves.
Factors affecting the binding curves measured by radioimmunoassay are examined by comparing theoretical binding curves calculated for ideal populations of homogeneous antibodies and antigens in order to test the conclusions of Berzofsky et al. [Berzofsky, J. A., Curd, J. G., & Schechter, A. N. (1976) Biochemistry 15, 2113--2121] about the effect of multiple antigenic determinants on the shapes of such curves. When such ideal binding curves with the same midpoints and limiting values expected for univalent and multivalent antigens are compared, it is clear that multivalent antigens do not produce abnormally steep binding curves but rather tend somewhat to produce less steep curves. Under practical experimental circumstances, the binding curves for univalent and multivalent antigens are predicted to be indistinguishable in shape. Some alternative causes of abnormally steep binding curves are suggested.


Fine needle aspiration cytology diagnosis of aneurysmal bone cyst: a case report.
Aneurysmal bone cyst is a relatively rare tumour accounting 1 to 6% of all primary bone tumours. The involvement of clavicle is even rare with incidence of only 3% of all cases of aneurysmal bone cyst. Aneurysmal bone cyst is an expanding osteolytic lesion occurring mostly at metaphyseal ends of the long bones. Although excisional biopsy is diagnostic for aneurysmal bone cyst and FNAC (fine needle aspiration cytology) is mostly inconclusive. Still FNAC can be helpful in pre-operative diagnosis of aneurysmal bone cyst.


The Impact of COVID-19 on Values and Religiosity in a Multi-Ethnic Population.
We investigated the COVID-19 pandemic's impact on values and religiosity in multi-ethnic Malaysia. Values were measured as changes in values, daily activities, and life priorities using a 5-point Likert scale (-2 to +2). Centrality of Religiosity Scale measured changes in religiosity. Around 176 predominantly female (66.5%), Chinese (68.2%) respondents, aged 35.5 ± 14.1 completed the survey. Most life values changed positively: a sense of security at home (2, interquartile range [IQR]: 1-2), connection with family (1, 1-2), and contribution to society (1, 1-2). Certain life priorities' importance increased: health (2, IQR 2-2), family (2, 2-2), and happiness (2, 1-2); except power and money. These significant positive changes in values and religiosity varied between genders and ethnicities.


The millennium bug: health and medicine around the year 1000.
This introductory paper has two main themes: first, what can be said about the diseases characteristic of the period in question; second, what generalizations are possible about the medicine that could be deployed against them. After a preliminary discussion of the extent to which the system of dating from Christ's incarnation governed the chronology of those who fall within our scope, the paper raises the question of whether the year 1000 prompted millenial 'fever'. This leads into an account of the concept of 'pathocoenosis', a tableau of the interrelated diseases prevalent at any one place and time. The limitations of the tenth- to eleventh-century evidence available for such a project are examined, philosophical objections to disease history reviewed, and agenda for future research outlined. The paper then turns to the main features of the medical texts on which any investigation of therapeutic practice in the early Middle Ages must depend: features such as amorphousness, mutability, lack of theory, elusive connection with clinical reality. Finally, some wider implications of the special issue are delineated-concerning presumed contrasts between East and West, and, with respect to the relationship of theory to practice, between early and later Middle Ages.


[Prehospital management of acute myocardial infarction. Data from a consecutive cohort of 115 patients in a French region in 2002].
The treatment of acute myocardial infarction is in evolution. Several strategies are utilized ranging from thrombolysis to percutaneous angioplasty (PCI), and the combination of both treatments; the latter providing an interesting compromise between treatment delay and efficiency of early myocardial reperfusion. We reviewed the early treatment strategies of acute myocardial infarctions undertaken by Samu in region 6 (south west of France) in 2002. Of a cohort of 115 patients, 83 patients (72.1%) had a revascularisation strategy: 56 (48.7%) had a primary PCI, and 27 (23.4%) had thrombolysis (92.6% being performed in the prehospital treatment). In those undergoing thrombolysis, 13 patients (48%) had ongoing features of ischaemia; excluding 4 patients who died during transport, all had a PCI at the admission in hospital. For the 14 patients with successful thrombolysis, 5 had facilitated PCI at the admission, 8 had a delayed angioplasty and 1 patient did not have angiography. Although the number of patients receiving thrombolysis in this study was small, this treatment was begun 62 minutes before primary PCI. There are important intra and extra hospital delays to the commencement of PCI. The easy utility of thrombolysis together with the potential to PCI argue in favour for a strategy of prehospital thrombolysis associated with a facilitated angioplasty.


Single-Channel Recording of Glycine Receptors in Human Embryonic Kidney (HEK) Cells.
This protocol describes how to record the single-channel activity of recombinant homomeric glycine receptors expressed in human embryonic kidney (HEK) cells. Cell-attached recordings readily reveal the large conductance (90 pS) and distinctive clusters of activations at high glycine concentration. This method for obtaining equilibrium recordings can be adapted to any ion channel receptor. The necessary extensions to outside-out patch for nonequilibrium recordings are also described, as are basic analyses of channel properties and activity.


A Rare Case of Third Ventricular Glioblastoma.
Glioblastoma, also known as glioblastoma multiforme, is an aggressive type of cancer that is made up of abnormal astrocytic cells, but also contain a mixture of different cell types (including blood vessels) and areas of necrosis. It is often seen in the brain and spinal cord, but glioblastomas are rarely found in the third ventricle. In this case, it was diagnosed in a 22-year-old male patient and we intended to draw attention to its atypical localization and surgical access to this third ventricle glioblastoma.


Short-term effects of hypothermia on axonal injury, preoligodendrocyte accumulation and oligodendrocyte myelination after hypoxia-ischemia in the hippocampus of immature rat brain.
Hypothermia is known to improve neurological recovery of animals and humans exposed to hypoxic-ischemic (HI) injury. However, the underlying mechanisms of the neuroprotective effects of hypothermia are only partially understood, including decreased excitotoxicity and apoptosis, and suppressed inflammation. There are few studies about the hypothermic effects on axonal injury and oligodendrocyte (OL) lineage degeneration, which are important components of neonatal brain injuries that cause cognitive disability. We hypothesized that mild hypothermia would reduce axonal injury and increase myelination in the hippocampus after HI. We performed left carotid artery ligation followed by 8% oxygen for 2 h in 7-day-old rats. Animals were divided into a hypothermic group (rectal temperature 32-33°C for 24 h) and a normothermic group (36-37°C for 24 h) immediately after HI. Animals were sacrificed at 1, 3 and 7 days for immunohistochemistry or Western blot analysis. We detected neuron loss by microtubule-associated protein 2 labeling and axonal injury by non-phosphorylated neurofilament (SMI32) with neurofilament 200 (NF200) double staining. We examined early OL progenitors by A2B5 or NG2, preoligodendrocytes (preOLs) by O4, and mature OLs by 2,3-cyclic nucleotide 3-phosphodiesterase (CNPase) and glutathione S-transferase (GST)-pi staining. Apoptosis was studied by active caspase-3. Hypothermia was associated with a significant elevation of neurons and axons in the hippocampal CA1 region after HI. Early OL progenitors (A2B5(+)) were elevated, but preOLs (O4(+)) and active caspase-3 were dramatically reduced in the hypothermic rat brain. Further study showed that the apoptotic rate of preOLs (caspase-3(+)-O4(+)/O4(+)) was markedly attenuated by hypothermic treatment compared to normothermic animals. The immunoreactivity of CNPase and GST-pi and the protein level of the myelin basic protein significantly increased in the hippocampus of hypothermia-treated rat brain. Axonal myelination also increased in hypothermic animals, which were tested by myelin basic protein and NF200 double staining and electron microscopy. These results showed that hypothermia reduced HI damage to axons and OL myelination coincided with increased early OL progenitor proliferation and decreased preOL accumulation and apoptosis. This study suggested new aspects that may contribute to elucidate the mechanism of hypothermic neuroprotection in neonatal rat brain.


The prospects for constraining productivity through time with the whole-plant physiology of fossils.
Anatomically preserved fossils allow estimation of hydraulic parameters, potentially providing constraints on interpreting whole-plant physiology. However, different organ systems have typically been considered in isolation - a problem given common mismatches of high and low conductance components coupled in the hydraulic path of the same plant. A recent paper addressed the issue of how to handle resistance mismatches in fossil plant hydraulics, focusing on Carboniferous medullosan seed plants and arborescent lycopsids. Among other problems, however, a fundamental error was made: the transpiration stream consists of resistances in series (where resistances are additive and the component with the largest resistance can dominate the behavior of the system), but emphasis was instead placed on the lowest resistance, effectively treating the system as resistances in parallel (where the component with the smallest resistance will dominate the behavior). Instead of possessing high assimilation capacities to match high specific stem conductances, it is argued here that individual high conductance components in these Paleozoic plants are nonetheless associated with low whole-plant productivity, just as can be commonly seen in living plants. Resolution of how to handle these issues may have broad implications for the Earth system including geobiological feedbacks to rock weathering, atmospheric composition, and climate.


Comparison of radiation-induced damage between CT angiography and conventional coronary angiography.
Both computed tomography (CTA) and conventional angiography (CCA) can provide direct visualization of the coronary arteries. The aim of the present study was to compare the radiation exposure between CTA and CCA and to search whether this amount of radiation causes significant DNA damage. Seventy-two patients who underwent CTA or CCA were enrolled prospectively. We recorded the radiation dosage that was used during the procedures and calculated the effective dose (ED). We determined the sister chromatid exchange (SCE) level from the blood samples which were drawn from the patients before and after the procedures. The change in SCE is used as the measure of DNA damage induced by the radiation. The patients in the CTA (n = 36) and CCA groups (n= 36) had similar baseline characteristics. The ED was higher in CTA examinations compared to CCA examinations (14.2 +/- 2.7 vs 6.4 +/- 3.1, P <0.001). The SCE level increased significantly after both angiography methods (P <0.001). When the change in SCE after angiography was compared, we did not find a significant difference among the groups (2.73 +/- 1.6 vs 2.54 +/- 1.22, P= NS). Although the patients who underwent CTA were exposed to a greater amount of radiation, the radiation-induced genetic damage was similar with both types of the procedures.


Ceftriaxone treatment of penicillinase-producing Neisseria gonorrhoeae infections in children.
The incidence of penicillinase-producing Neisseria gonorrhoeae (PPNG) among adults with gonorrhea in Brooklyn now exceeds 24%. Because children usually acquire their infection from adults, it follows that we have had a concomitant rise in PPNG among sexually abused children. The Centers for Disease Control now recommends ceftriaxone for the first line treatment of gonorrhea but there are no data as to its use in children for this indication. From May, 1987, through March, 1989, 33 children, 4 days to 10 years of age, were admitted to Kings County Hospital for 34 episodes of gonorrhea. Nine (26.5%) were caused by PPNG. Twenty-three were female; 10 were male. There were 17 isolates from the vagina, 3 from the urethra, 9 from the pharynx, 9 from the rectum and 6 from the eye. Eight children (all girls) had infections at greater than or equal to 1 site; 2 were infected at 3 sites. Twenty-eight children were sexually abused and 5 were neonates with ophthalmia (1 PPNG). All isolates were susceptible to ceftriaxone by disc diffusion testing. Agar dilution was performed for 18 isolates; minimal inhibitory concentrations to ceftriaxone were less than or equal to 0.06 mg/liter. The 5 PPNG isolates tested had minimal inhibitory concentrations to penicillin of 2 to 16 mg/liter and 3 isolates were resistant to tetracycline with minimal inhibitory concentrations of 32 mg/liter. Twenty-eight children were treated with a single dose of ceftriaxone, including the 5 neonates with ophthalmia; the dose was 125 mg if less than 45 kg or 250 mg if greater than 45 kg.(ABSTRACT TRUNCATED AT 250 WORDS)


A 15N stable isotope semen label to detect mating in the malaria mosquito Anopheles arabiensis Patton.
In previous studies it was determined that the stable isotope 13-carbon can be used as a semen label to detect mating events in the malaria mosquito Anopheles arabiensis. In this paper we describe the use of an additional stable isotope, 15-nitrogen (15N), for that same purpose. Both stable isotopes can be analysed simultaneously in a mass spectrometer, offering the possibility to detect both labels in one sample in order to study complex and difficult-to-detect mating events, such as multiple mating. 15N-glycine was added to larval rearing water and the target enrichment was 5 atom% 15N. Males from these trays were mated with unlabelled virgin females, and spiked spermathecae were analysed for isotopic composition after mating using mass spectrometry. Results showed that spermathecae positive for semen could be distinguished from uninseminated or control samples using the raw delta15N per thousand values. The label persisted in spermathecae for up to 5 days after insemination, and males aged 10 days transferred similar amounts of label as males aged 4 days. There were no negative effects of the label on larval survival and male longevity. Enrichment of teneral mosquitoes after emergence was 4.85 +/- 0.10 atom% 15N. A threshold value defined as 3 standard deviations above the mean of virgin (i.e. uninseminated spermathecae) samples was successful in classifying a large proportion of samples correctly (i.e. on average 95%). We conclude that alongside 13C, 15N can be used to detect mating in Anopheles and the suitability of both labels is briefly discussed.


A Case of Microscopic Polyangiitis Complicated by Mucormycosis: A Dangerous Balancing Act.
Microscopic polyangiitis (MPA) is a rare antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis marked by renal involvement, which often leads to rapidly progressive glomerulonephritis. Immunosuppressive treatment is necessary to prevent irreparable organ damage. On the other hand, mucormycosis is a rare and devastating opportunistic fungal infection with a high mortality rate in both immunosuppressed and immunocompetent individuals. It requires a high index of suspicion at the time of diagnosis since any delay in treatment may lead to severe morbidity or death. Here, we present the case of a diabetic patient diagnosed with MPA who received partial induction treatment, subsequently developed mucormycosis, survived, yet required continued immunosuppressive treatment for active MPA while imaging was concerning for a persistent mucormycosis infection. This case highlights the barriers to early mucormycosis detection specific to vasculitis patients, mucormycosis considerations unique to the rheumatologic population, and discusses how to balance immunosuppressive treatment in the setting of a deadly opportunistic infection.


Toward a statistical validation of brain signatures as robust measures of behavioral substrates.
The "brain signature of cognition" concept has garnered interest as a data-driven, exploratory approach to better understand key brain regions involved in specific cognitive functions, with the potential to maximally characterize brain substrates of behavioral outcomes. Previously we presented a method for computing signatures of episodic memory. However, to be a robust brain measure, the signature approach requires a rigorous validation of model performance across a variety of cohorts. Here we report validation results and provide an example of extending it to a second behavioral domain. In each of two discovery data cohorts, we derived regional brain gray matter thickness associations for two domains: neuropsychological and everyday cognition memory. We computed regional association to outcome in 40 randomly selected discovery subsets of size 400 in each cohort. We generated spatial overlap frequency maps and defined high-frequency regions as "consensus" signature masks. Using separate validation datasets, we evaluated replicability of cohort-based consensus model fits and explanatory power by comparing signature model fits with each other and with competing theory-based models. Spatial replications produced convergent consensus signature regions. Consensus signature model fits were highly correlated in 50 random subsets of each validation cohort, indicating high replicability. In comparisons over each full cohort, signature models outperformed other models. In this validation study, we produced signature models that replicated model fits to outcome and outperformed other commonly used measures. Signatures in two memory domains suggested strongly shared brain substrates. Robust brain signatures may therefore be achievable, yielding reliable and useful measures for modeling substrates of behavioral domains.


Electron beam tomography and angiography: sex differences.
We sought to study a large cohort of symptomatic women to determine the clinical use of electron beam tomography (EBT), with evaluation of the sensitivity and specificity of obstructive coronary disease and the differences between premenopausal and postmenopausal cohorts. Patients who underwent angiography for evaluation of coronary artery disease (CAD) and EBT within 3 months were enrolled. Receiver operating characteristic curves were used to establish relationships between EBT calcium scores and angiographic disease. We studied 1120 symptomatic patients, 387 women and 733 men. We found no significant differences with respect to sensitivity for obstructive disease (96% in men and women). However, women had a significantly higher specificity (46% in men versus 57% in women; P =.01). The area under the curves for coronary calcium score predicting angiographic disease was 0.85 for all patients and 0.84 in women. Evaluation of scores on the basis of age revealed a 14.4-year lag between men and women. One hundred thirty-five women had negative EBT study results (score, zero; no calcium present), with 6 with single-vessel disease and 129 with normal coronaries or nonobstructive disease only (negative predictive value, 96%). EBT may have a great value in evaluation of women with possible CAD. The high sensitivity and high negative predictive value may serve as the basis for a new diagnostic approach to filter symptomatic women with suspected CAD before coronary angiography.


Periprosthetic Fracture through a Unicortical Tracking Pin Site after Computer Navigated Total Knee Replacement.
A rare complication from computer-navigated total knee arthroplasty is a fracture through the insertion site of a tracking pin. These pins are inserted across the femoral and tibial shafts either bicortically, transcortically, or unicortically and have a reported fracture incidence of 1.38%, with all published cases occurring after bicortical pin placement. In this case, a 60-year-old female suffered a femoral shaft fracture through a unicortically inserted computer navigation tracking pin 6 weeks after total knee arthroplasty. Her fracture was successfully fixated with an intramedullary nail with retention of the knee prosthesis. This case is important as it records the risk for a postoperative fracture through a unicortically inserted computer navigation pin.


Influence of Ametropia and Its Correction on Measurement of Accommodation.
Amplitude of accommodation (AA) is reportedly greater for myopic eyes than for hyperopic eyes. We investigated potential explanations for this difference. Analytical analysis and computer ray tracing were performed on two schematic eye models of axial ametropia. Using paraxial and nonparaxial approaches, AA was specified for the naked and the corrected eye using the anterior corneal surface as the reference plane. Assuming that axial myopia is due entirely to an increase in vitreous chamber depth, AA increases with the amount of myopia for two reasons that have not always been taken into account. First is the choice of reference location for specifying refractive error and AA in diopters. When specified relative to the cornea, AA increases with the degree of myopia more than when specified relative to the eye's first Gaussian principal plane. The second factor is movement of the eye's second Gaussian principal plane toward the retina during accommodation, which has a larger dioptric effect in shorter eyes. Using the corneal plane (placed at the corneal vertex) as the reference plane for specifying accommodation, AA depends slightly on the axial length of the eye's vitreous chamber. This dependency can be reduced significantly by using a reference plane located 4 mm posterior to the corneal plane. A simple formula is provided to help clinicians and researchers obtain a value of AA that closely reflects power changes of the crystalline lens, independent of axial ametropia and its correction with lenses.


Effect of selenium and vitamin E on the development of immunity to coccidiosis in chickens.
Six experiments were conducted using broiler chickens to study the effect of selenium (Se) or vitamin E supplementation of a corn-soybean meal diet on the immune response to coccidiosis. Immunized chickens fed diets supplemented with .25 ppm Se or 100 IU vitamin E/kg of diet had increased body weight gain and feed intake and a tendency for lower feed conversion ratio than chickens fed unsupplemented diet after a challenge with 150,000 oocysts of Eimeria tenella. In two experiments, chickens fed .25 and .50 ppm of Se and immunized against E. tenella had higher body weight gain and a tendency for higher feed intake and lower feed conversion ratio than unsupplemented chickens when challenged with 150,000 oocysts of E. tenella. Except for a reduction on cecal lesion scores and blood packed cell volume in Experiments 1 and 4, respectively, no dietary effect was observed on cecal lesion score or blood packed cell volume of immunized chickens. Dietary supplementation with selenium or vitamin E reduced mortality and increased body weight gain of nonimmunized chickens infected with E. tenella in three of four experiments. These studies suggest that immunization of chickens against coccidiosis is enhanced by Se or vitamin E supplementation.


Effects of vitamin C supplementation on glycaemic control: a systematic review and meta-analysis of randomised controlled trials.
Randomised controlled trials (RCTs) have observed contrasting results on the effects of vitamin C on circulating biomarkers of glycaemic and insulin regulation. We conducted a systematic review and meta-analysis of RCTs testing the effect of vitamin C administration on glucose, HbA1c and insulin concentrations. Four databases (PubMed, Embase, Scopus and Cochrane Library) were used to retrieve RCTs published from inception until April 2016 and testing the effects of vitamin C in adult participants. The screening of 2008 articles yielded 22 eligible studies (937 participants). Overall, vitamin C did not modify glucose, HbA1c and insulin concentrations. However, subgroup analyses showed that vitamin C significantly reduced glucose concentrations (-0.44 mmol/l, 95% CI: -0.81, -0.07, P=0.01) in patients with type 2 diabetes and in interventions with a duration greater than 30 days (-0.53%, 95% CI: -0.79, -0.10, P=0.02). Vitamin C administration had greater effects on fasting (-13.63 pmol/l, 95% CI: -22.73, -4.54, P<0.01) compared to postprandial insulin concentration. Meta-regression analyses showed that age was a modifier of the effect of vitamin C on insulin concentration. Furthermore, the effect size was associated with baseline BMI and plasma glucose levels, and with the duration of the intervention. In conclusion, greater reduction in glucose concentrations observed in patients with diabetes, older individuals and with more prolonged supplementation. Personalised interventions with vitamin C may represent a feasible future strategy to enhance benefits and efficacy of interventions. Nevertheless, results need to be interpreted cautiously due to limitations in the primary studies analysed.


The rhizosphere microbiome improves the adaptive capabilities of plants under high soil cadmium conditions.
Cadmium (Cd) contamination of agricultural soils poses a potential public health issue for humans. Phytoremediation-based accumulating plants are an effective and sustainable technology for Cadmium remediation of contaminated agricultural soil. The rhizosphere microbiome can promote the growth and Cadmium accumulation in hyperaccumulators, but its taxonomic and functional traits remain elusive. The present study used two ecotypes of Sedum alfredii, an accumulating ecotype (AE) and a non-accumulating ecotype (NAE), as model plants to investigate the rhizosphere microbiome assemblages and influence on plant growth under high cadmium conditions. Our results showed that distinct root microbiomes assembled in association with both ecotypes of S. alfredii and that the assemblages were based largely on the lifestyles of the two ecotypes. In addition, we demonstrated that the functions of the microbes inhabiting the rhizosphere soils were closely associated with root-microbe interactions in both ecotypes of S. alfredii. Importantly, our results also demonstrated that the rhizosphere microbiome assembled in the AE rhizosphere soils contributed to plant growth and cadmium uptake under high cadmium conditions through functions such as nitrogen fixation, phosphorus solubilization, indole acetic acid (IAA) synthesis, and siderophore metabolism. However, this phenomenon was not clearly observed in the NAE. Our results suggest that the rhizosphere microbiome plays important roles in biogeochemical nutrient and metal cycling that can contribute to host plant fitness.


Access towards enantiopure α,α-difluoromethyl alcohols by means of sulfoxides as traceless chiral auxiliaries.
A new methodology to access enantiopure α,α-difluoromethyl alcohols is hereby being described. The strategy relies on the use of an enantiopure aryl α,α-difluoromethyl sulfoxide employed as chiral and removable auxiliary for the stereoselective difluoromethylation of carbonyl derivatives. The obtained α,α-difluoro-β-hydroxysulfoxides displayed unprecedented diastereomeric ratios.


HIV-Associated Urogenital Malignancies.
Non-AIDS-defining malignancies (NADM) are a leading cause of morbidity and mortality for HIV-infected subjects. The risk of testicular germ cell cancer (GCC) and renal cell cancer is slightly increased in the setting of HIV, whereas there is a slightly decreased risk of prostate cancer and bladder cancer. As in industrialized countries the majority of people living with HIV are men, and people aged 55 and older now account for more than a quarter of persons living with HIV, both testis and prostate cancer are assumed to occur with increased frequency in HIV-infected subjects. Overall, treatments should be the same as in HIV-negative patients with urogenital malignancies. Since the introduction of combination antiretroviral therapy (cART) the outcome appears to have improved due to a decrease in HIV-related deaths. HIV-infected men who are treated with standard therapies for GCC now have a similar cancer-free survival compared with their HIV-negative counterparts. Screening and treatment for prostate cancer should follow recommendations established for HIV-negative men. During radio- or chemotherapy patients should receive concurrent cART but the drug-drug interaction potential must be taken into account.


Microgravity-induced alterations in cultured testicular cells.
Cultured STe cells (2n karyotype) from swine testis were submitted to simulated microgravity using a 3D Random Positioning Machine for 5 min., 15 min., 30 min., 1 h and 23 h. Sample processing included: histological characterization of cell types, immunohistochemical identification of (i) microtubules (a-tubulin), (ii) alkaline phosphates, (iii) 3 beta-hydroxy-steroid-dehydrogenase (3?-HSDH), and histochemical lipid analyses. After 5 min. simulated microgravity a slight microtubule disorganisation occurred, which increased dramatically with increasing microgravity duration. After 23 h microtubule arrays were completely disrupted. 3 beta-HSDH immunostaining was detectable only in one cell type: under control conditions and 5 min. into microgravity immunoreactivity was strong, but completely disappeared thereafter. Immunostaining intensity for alkaline phosphates, a good marker for myoid cells, decreased after 15 min. in microgravity.


New prehospital scoring system for traumatic brain injury to predict mortality and severe disability using motor Glasgow Coma Scale, hypotension, and hypoxia: a nationwide observational study.
Assessing the severity of injury and predicting outcomes are essential in traumatic brain injury (TBI). However, the respiratory rate and Glasgow Coma Scale (GCS) of the Revised Trauma Score (RTS) are difficult to use in the prehospital setting. This investigation aimed to develop a new prehospital trauma score for TBI (NTS-TBI) to predict mortality and disability. We used a nationwide trauma database on severe trauma cases transported by fire departments across Korea in 2013 and 2015. NTS-TBI model 1 used systolic blood pressure <90 mmHg, peripheral capillary oxygen saturation <90% measured via pulse oximeter, and motor component of GCS. Model 2 comprised variables of model 1 and age >65 years. We assessed discriminative power via area under the curve (AUC) value for in-hospital mortality and disability defined according to the Glasgow Outcome Scale with scores of 2 or 3. We then compared AUC values of NTS-TBI with those of RTS. In total, 3,642 patients were enrolled. AUC values of NTS-TBI models 1 and 2 for mortality were 0.833 (95% confidence interval [CI], 0.815 to 0.852) and 0.852 (95% CI, 0.835 to 0.869), respectively, while AUC values for disability were 0.772 (95% CI, 0.749 to 0.796) and 0.784 (95% CI, 0.761 to 0.807), respectively. AUC values of NTS-TBI model 2 for mortality and disability were higher than those of RTS (0.819 and 0.761, respectively) (P<0.01). Our NTS-TBI model using systolic blood pressure, motor component of GCS, oxygen saturation, and age was feasible for prehospital care and showed outstanding discriminative power for mortality.


A cell wall-active lipopeptide from the fungus Pochonia bulbillosa.
Bioassay-directed fractionation of a fermentation of Pochonia bulbinosa, culture 38G272, led to the isolation of a series of structurally novel, prospective cell wall-active lipopeptides. The main component of this suite is 1, a linear hexapeptide with a delta-hydroxymyristic acid amide substituted N-terminus. The structure was deduced using high-field microsample NMR, Fourier transform mass spectrometry, and microscale chemical degradation. The potent cell wall activity and synthetically accessible structure of 1 make it a potential lead for further investigation.


Low concentration of S100A8/9 promotes angiogenesis-related activity of vascular endothelial cells: bridges among inflammation, angiogenesis, and tumorigenesis?
Previous studies showed that several members of the S100A family are involved in neovascularization and tumor development. This study checked whether low concentrations of S100A8 or S100A9 has any effect on the behaviour of vascular endothelial cells. A human umbilical vascular endothelial cell (HUVEC) line was used to measure vascular endothelial cell bioactivity related to angiogenesis, such as cell proliferation, migration, and vessel formation. In the low concentration range up to 10 μg/mL, either each alone or in combination, S100A8 and S100A9 proteins promoted proliferation of HUVEC cells in a dose-dependent manner. The presence of both proteins in culture showed additive effects over each single protein. Both proteins enhanced HUVEC cells to migrate across the transwell membrane and to form tube-like structures on the Matrigel surface. When mixed in Matrigel and injected subcutaneously in Balb/c mice, both proteins increased vessel development in the gel plugs. Microarray assay of HUVEC cells treated with 10 μg/mL S100A8 revealed that ribosome pathway, pathogenic Escherichia coli infection pathway, apoptosis, and stress response genes were modulated by S100A8 treatment. We propose that S100A8 and S100A9 proteins from either infiltrating inflammatory cells or tumor cells play an important role in the interplay among inflammation, angiogenesis, and tumorigenesis.


A novel triterpenoid isolated from apple functions as an anti-mammary tumor agent via a mitochondrial and caspase-independent apoptosis pathway.
A novel triterpenoid, named 3β-trans-cinnamoyloxy-2α-hydroxy-urs-12-en-28-oic acid (CHUA), was one of the main components of apple peels and showed potent in vitro antitumor activity against human tumor cells. In vivo antitumor experiments showed that CHUA could significantly inhibit the growth of mammary tumor in a nude mouse xenograft model at a dose of 50 mg/kg/day without body weight loss and mortality. In vitro, CHUA could induce apoptosis in MDA-MB-231 cells through the detection of DNA fragments and LDH activity. Simultaneously, mitochondrial transmembrane potential was markedly reduced and the release of cytochrome c was increased after CHUA treatment. It also up-regulated the expression ratio of mitochondrial Bax/Bcl-2 regulated by SIRT1 and p53. Interestingly, z-VAD-fmk and z-DEVD-fmk augmented cell death after CHUA treatment. Other protease(s) different from caspase-3 might be responsible for the degradation of PARP. These results suggested that the pro-apoptotic activity of CHUA may be adjusted by mitochondrial and caspase-independent pathways.


Guiding principles for technical infrastructure to support computable biomedical knowledge.
Over the past 4 years, the authors have participated as members of the Mobilizing Computable Biomedical Knowledge Technical Infrastructure working group and focused on conceptualizing the infrastructure required to use computable biomedical knowledge. Here, we summarize our thoughts and lay the foundation for future work in the development of CBK infrastructure, including: explaining the difference between computable knowledge and data, and contextualizing the conversation with the Learning Health Systems and the FAIR principles. Specifically, we provide three guiding principles to advance the development of CBK infrastructure: (a) Promote interoperable systems for data and knowledge to be findable, accessible, interoperable, and reusable. (b) Enable stable, trustworthy knowledge representations that are human and machine readable. (c) Computable knowledge resources should, when possible, be open. Standards supporting computable knowledge infrastructures must be open.


Saturated fats, dairy foods and cardiovascular health: No longer a curious paradox?
Cardiovascular diseases (CVDs) are a major cause of death and morbidity in many parts of the world, and many dietary guidelines limit the intake of saturated fatty acids (SFA) as they are regarded as an important risk factor for CVDs due to their association with increased blood cholesterol. Dairy foods are often a major contributor to dietary intake of SFA, and since many dietary guidelines contain restrictions on SFA intake, this can lead to a moderation of dairy food intake despite meta-analyses generally showing dairy to have a neutral or negative association with CVDs. Many prospective studies and randomised controlled trials do not support a simple positive association between SFA intake and the risk of atherosclerotic CVD and its components although some early studies had a number of methodological weakness. Studies that included blood cholesterol data do broadly support the positive relationship between SFA and blood low-density lipoprotein cholesterol (LDL-C) but without increased CVD risk resulting, despite LDL being a causal factor in atherosclerotic CVD. These data suggest that LDL-C alone is not a consistently good predictor or cause of CVD risk, perhaps particularly in relation to dairy food consumption although some non-dairy food studies have also shown LDL-C reduction was not reflected in reduced CVD risk. This narrative review examines some reasons for these findings. Overall, restrictions on dairy food intake do not seem warranted, although there remains a need to further understand the association of different dairy food types with chronic diseases, perhaps particularly for type 2 diabetes.


Elimination Diets for Irritable Bowel Syndrome: Approaching the End of the Beginning.
Dietary interventions have become a mainstay of treating patients with irritable bowel syndrome (IBS). Most of the available studies have focused on the benefits of elimination diets. While elimination diets can be highly effective, they should be avoided in patients with 2 emerging eating disorders: orthorexia nervosa and avoidant/restrictive food intake disorder. Similar to drug therapies, diet interventions are effective for only a subgroup of patients with IBS. They should be viewed as "a" therapy not "the" therapy for patients with IBS. It will be critical to develop strategies that utilize symptoms combined with biomarkers which parse patients with IBS by pathophysiology and in so doing, help providers to pick the right treatment for the right patient. At present, diet interventions are primarily focused on elimination of certain foods but there are an increasing number of supplementation studies which are lending support to the concept of "functional foods."


[Development of a colloidal gold based immunochromatographic strip for 8-OHdG detection].
8-hydroxy-2'-deoxyguanosine (8-OHdG) is a sensitive and stable biomarker for evaluating DNA oxidative damage. A rapid and sensitive colloidal gold immunochromatographic strip was developed for 8-OHdG detection by a competitive method. The sample pad (glass cellulose film), bonding pad (glass cellulose film), nitrocellulose film and absorbent pad were pasted on the polyvinyl chloride (PVC) base plate to construct the test strip. Colloidal gold (AuNPs) was prepared by the reduction of chloroauric acid with sodium citrate. 8-OHdG antibody (Ab) was coated on the outer layer of AuNPs to form Ab@AuNPs as a probe. Bovine serum albumin (BSA) and 8-OHdG were conjugated with carbodiimide hydrochloride to prepare an artificial antigen, which was used as the coating antigen of detection line. Goat anti mouse polyclonal antibody IgG was used as the coating antibody of control line. The experimental parameters were optimized including the type of nitrocellulose membrane, the formula of loading solution, and the spraying amount of gold labeled antibody. The results showed that the appropriate nitrocellulose membrane was CN 95. The optimal loading solution included BSA (1%), Tween-20 (3%), sucrose (3%) and NaCl (0.9%). The optimal spraying amount of gold labeled antibody was 4 μL. 8-OHdG can be detected by the strip under visible light, and the level of 8-OHdG in urine can be preliminarily determined by comparing the color intensity of T line and C line. The 8-OHdG concentration in urine was further calculated by the gray value of T line and the threshold of detection was 2.55 μg/L. This colloidal gold immunochromatographic strip is simple, rapid and specific for detecting 8-OHdG in human urine to preliminarily evaluate the human status.


Explant Methodology for Analyzing Neuroblast Migration.
The subventricular zone (SVZ) in the mammalian forebrain contains stem/progenitor cells that migrate through the rostral migratory stream (RMS) to the olfactory bulb throughout adulthood. SVZ-derived explant cultures provide a convenient method to assess factors regulating the intermediary stage of neural stem/progenitor cell migration. Here, we describe the isolation of SVZ-derived RMS explants from the neonatal mouse brain, and the conditions required to culture and evaluate their migration.


Interaction of Human Dendritic Cells with Graphene Oxide Nanoparticles In Vitro.
We studied the effect of graphene oxide nanoparticles on the differentiation of human dendritic cells and uptake of nanoparticles by these cells in vitro. The objects of the study were mononuclear cells from healthy donors induced into the phenotype of dendritic cells by cytokines (IL-6 and GM-CSF). We used graphene oxide nanoparticles of different sizes functionalized with linear or branched PEG (P-GO or bP-GO) in concentrations of 5 and 25 μg/ml. It was found that graphene oxide nanoparticles did not affect the viability and percentage of dendritic cells in the culture. However, P-GO nanoparticles (25 μg/ml) suppressed the expression of CD83 on the surface of dendritic cells in cultures, thereby suppressing cell differentiation. Dendritic cells internalized P-GO nanoparticles, particles in high concentration were more actively engulfed, but the size of the particles and the type of PEG did not affect the intensity of this process. In general, P-GO nanoparticles in a concentration of 25 μg/ml can regulate differentiation of dendritic cells by suppressing their maturation.


Biochemical differences between staurosporine-induced apoptosis and premature mitosis.
Apoptosis is morphologically related to premature mitosis, an aberrant form of mitosis. Staurosporine, a potent protein kinase inhibitor, induces not only apoptotic cell death in a wide variety of mammalian cells but also premature initiation of mitosis in hamster cells that are arrested in S phase by DNA synthesis inhibitors. Here we report on the biochemical differences between the two phenomena commonly caused by staurosporine. Rat 3Y1 fibroblasts that had been arrested in S phase with hydroxyurea underwent apoptosis by treatment with staurosporine, whereas S-phase-arrested CHO cells initiated mitosis prematurely when similarly treated with a low concentration of staurosporine. Chromosome condensation occurred in both apoptosis (3Y1) and premature mitosis (CHO). However, neither formation of mitotic spindles nor mitosis-specific phosphorylation of MPM-2 antigens was observed in apoptosis of 3Y1 cells, unlike premature mitosis of CHO cells. The p34cdc2 kinase activated in normal and prematurely mitotic cells remained inactive in the apoptotic cells, probably because the active cyclin B/p34cdc2 complex was almost absent in the S-phase-arrested 3Y1 cells. The absence of intracellular activation of p34cdc2 in apoptosis was confirmed by immunohistochemical analyses using a specific antibody raised against Ser55-phosphorylated vimentin which is specifically phosphorylated by p34cdc2 during M phase. Furthermore, phosphorylation of histones H1 and H3, which is associated with mitotic chromosome condensation, did not occur in the apoptotic cells. These results indicate that the two phenomena, staurosporine-induced apoptosis and premature mitosis, are different in their requirement for p34cdc2 kinase activation and histone phosphorylation.


Orthogonality of diffractive deep neural network.
Some rules of the diffractive deep neural network (D2NN) are discovered. They reveal that the inner product of any two optical fields in D2NN is invariant and the D2NN acts as a unitary transformation for optical fields. If the output intensities of the two inputs are separated spatially, the input fields must be orthogonal. These rules imply that the D2NN is not only suitable for the classification of general objects but also more suitable for applications aimed at optical orthogonal modes. Our simulation shows the D2NN performs well in applications like mode conversion, mode multiplexing/demultiplexing, and optical mode recognition.


AJ Cronin and The Citadel: did a work of fiction contribute to the foundation of the NHS?
AJ Cronin (1896-1981) was a Scottish-born doctor-turned-novelist whose most famous novel is The Citadel, published in 1937. The book describes the struggles of an idealistic young doctor working in Wales and London in the 1920s and 30s. The novel was a global bestseller and its portrayal of a largely ineffective, corruption-ridden system of healthcare is thought to have directly influenced the foundation of the National Health Service in 1948. The Citadel anticipates such phenomena as evidence-based medicine and continuing medical education. This paper argues that the novel was never intended as propaganda for a state-controlled national health service. On the contrary, Cronin was against state control. Analysis of the novel is informed by recent biographical revelations about Cronin and the blurring of the margin between fact and fiction in Cronin's life and work is examined.


Decoy-state phase-matching quantum key distribution with source errors.
The phase-matching quantum key distribution (PM-QKD), one of the variants of Twin-Field (TF) QKD protocol, was recently proposed to overcome the rate-distance limits of point to point protocol without quantum repeaters. In this paper, we propose a more practical PM-QKD protocol version with four-intensity decoy states and source errors, since neither the infinite decoy states nor the precise control of the light source is available in practice. We present the formulation of the secure key rate of the proposed protocol and analyze the performances of the protocol with and without source errors by numerical simulations.


Associations between mast cells and laminin in oral lichen planus.
Mast cell numbers are increased significantly in oral lichen planus (OLP). In other inflammatory conditions, mast cells frequently adhere to extracellular matrix proteins such as laminin. The aim of this study, therefore, was to determine whether the distribution of mast cells in OLP is related topographically to laminin in vascular and epithelial basement membranes. Monoclonal antibodies for tryptase, laminin and the alpha6beta1 CD49f laminin-binding integrin were used to identify mast cells, basement membranes (blood vessels and basal epithelium) and the "classical" laminin adhesion receptor, respectively. A double-labelling immunoperoxidase technique was employed to examine and compare mast cell-laminin relationships in OLP (n=19) and normal buccal mucosa (NBM, n=13). In both OLP and NBM, the majority of mast cells were located close to vascular basement membranes. Quantitative studies revealed that the number of mast cells associated with the laminin of vascular basement membranes (distance <1 microm) was two-fold and three-fold higher, respectively, in the superficial and deep layers in OLP compared with NBM (P<0.001). The frequency distribution of mast cells associated with basal epithelium was not statistically different in both groups (P>0.05). The association of mast cells with laminin may be an important determinant of mast cell density in OLP During OLP lesion formation and progression, the preferential distribution of mast cells in the immediate perivascular region provides an ideal situation for mast cell-derived mediators to influence the vascular endothelium.


[The influence of the span of a bridge on oral epithelium. Cytoenzymatic examinations].
Cytoenzymatic examinations of epithelium in swabs taken from under metal and metal-acrylic bridges have been performed in 25 men without clinically perceptible changes in mucous membrane. Reactions on acid phosphatase, alkaline phosphatase and unspecific esterase have been performed. The results obtained point out that lysosomal enzymes are the factor damaging epithelium under the bridge. Damaging influence of the bridge on the epithelium has logical importance. It seems that keratosis process in epithelium cells under bridges starts off normally, however, it is not finished. Acryl monomer in the medium of oral cavity fluids probably plays essential role in formation of changes in the cells of intermediate and deep layers epithelium.


[Announcement of bad news and patient support].
Being unprepared for the announcement of bad news can influence patients' perception of their illness and upset their psychological balance. While the announcement of the diagnosis, the prognosis and the treatment remains a medical act, the psychological preparation around this announcement is a nursing act which forms an integral part of the nursing role.


Reduced alcohol use in patients prescribed pioglitazone.
Alcohol use disorder (AUD) is common and causes significant morbidity and mortality. Currently approved medications are moderately effective. Novel medications are needed to address AUD. Preliminary data suggests pioglitazone may reduce alcohol use. Veterans seen at the Minneapolis VA Health Care System, who were prescribed pioglitazone for diabetes between October 1, 2015 and September 30, 2016, were identified using a national VA database (N = 49). Further chart review was performed to identify all Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) scores prior to starting pioglitazone. Hierarchical Linear models were used to compare all AUDIT-C scores on and off pioglitazone and compare the change in AUDIT-C scores over time before and during pioglitazone was prescribed. AUDIT-C scores were nested within subject with fixed effects for pioglitazone and random intercept and slope for time. Forty-nine patients were prescribed pioglitazone and had AUDIT-C scores of 3 or more. The estimated mean AUDIT-C score prior to receiving pioglitazone was 3.98 (95% confidence interval [CI]: 3.51-4.44) and this was reduced to 2.89 (95% CI: 2.46-3.32), reflecting a significant change F(1, 323) = 43.3, p < .001 in the score. The primary reduction occurred within the first year of the pioglitazone prescription. This effect remained significant after controlling for age. This is the first study of pioglitazone used in a clinical sample focused on alcohol use outcome. The data show that pioglitazone may reduce alcohol use in patients with heavy drinking. Clinical trials of pioglitazone are warranted in patients with AUD.


Rapid Fabrication of Cell-Laden Alginate Hydrogel 3D Structures by Micro Dip-Coating.
Development of a simple, straightforward 3D fabrication method to culture cells in 3D, without relying on any complex fabrication methods, remains a challenge. In this paper, we describe a new technique that allows fabrication of scalable 3D cell-laden hydrogel structures easily, without complex machinery: the technique can be done using only apparatus already available in a typical cell biology laboratory. The fabrication method involves micro dip-coating of cell-laden hydrogels covering the surface of a metal bar, into the cross-linking reagents calcium chloride or barium chloride to form hollow tubular structures. This method can be used to form single layers with thickness ranging from 126 to 220 µm or multilayered tubular structures. This fabrication method uses alginate hydrogel as the primary biomaterial and a secondary biomaterial can be added depending on the desired application. We demonstrate the feasibility of this method, with survival rate over 75% immediately after fabrication and normal responsiveness of cells within these tubular structures using mouse dermal embryonic fibroblast cells and human embryonic kidney 293 cells containing a tetracycline-responsive, red fluorescent protein (tHEK cells).


Mapping of epitopes on Poa p I and Lol p I allergens with monoclonal antibodies.
Allergen Poa p I isolated from the dialysed aqueous extract of Kentucky blue grass pollen by affinity chromatography with an anti-Lol p I murine monoclonal antibody (MAb) 290A-167 was previously shown to consist of a 35.8-kilodalton (kD) component with a pI of 6.4, designated as Poa p Ia, and a 33-kD component with a pI of 9.1, designated as Poa p Ib. The present study reports on the comparative antigenic analyses of these two components, using MAbs produced separately against Poa p I and Lol p I. Thus, anti-Poa p I MAbs 60 and 61 and anti-Lol p I MAb 290A-167 recognized Poa p Ia and Poa p Ib whereas anti-Poa p I MAbs 62, 63 and 64 and anti-Lol p I MAb 348A-6 recognized only Poa p Ia. The specificities of the MAbs were further resolved by comparing their respective abilities to inhibit the binding of 125I-Poa p I or 125I-Lol p I to the different MAbs prepared in the form of solid phase. These studies revealed that at least 4 distinct epitopes (designated as E1, E2, E3 and E4) were shared by both Poa p I and Lol p I. All 4 epitopes were present on Poa p Ia whereas only E1 and E3 were detected on Poa p Ib. E1 was recognized by MAbs 60 and 61, E2 by MAbs 62, 63 and 64, E3 by MAb 290A-167 and E4 by MAb 348A-6.(ABSTRACT TRUNCATED AT 250 WORDS)


Healthcare utilization and costs associated with tyrosine kinase inhibitor switching in patients with chronic myeloid leukemia.
Differences in healthcare utilization and costs were examined in chronic myeloid leukemia (CML) patients experiencing first-, second- and third-line tyrosine kinase inhibitor (TKI) therapy. Three CML cohorts were identified from the Truven Health MarketScan® database: No-Switch Cohort (NSc) = did not switch from first-line; One-Switch Cohort (OSc) = switched from first- to second-line only; Two-Switch Cohort (TSc) = switched to second- and then third-line. A total of 3510 patients were identified (mean = 54%; age = 55.8 years). NSc comprised 81% of the sample, OSc comprised 15% and 4% were in the TSc. First-line utilization/costs were significantly higher in the OSc/TSc compared to the NSc. Second-line hospital/outpatient visits and costs were higher in TSc compared to OSc. TSc experienced a significant cost increase from first- to second-line ($4226.46), twice that of OSc ($2488.03). TKI switching is associated with a substantial increase in healthcare utilization and costs, particularly for patients who switch twice.


Pseudolaric acid B-induced autophagy contributes to senescence via enhancement of ROS generation and mitochondrial dysfunction in murine fibrosarcoma L929 cells.
Pseudolaric acid B (PAB) is the primary biologically active compound isolated from the root bark of P. kaempferi Gordon. Our previous study demonstrated that PAB induced mitotic catastrophe in L929 cells and indicated that only a small percentage (12%) of the cells undergoing mitotic catastrophe displayed an apoptotic phenotype after PAB treatment for 72 h. In this study, we found that a minority of the cells undergoing mitotic catastrophe ended in apoptosis, and a majority of them entered a period of senescence. Further data confirmed that PAB induced autophagy, reactive oxygen species (ROS) generation, and mitochondrial dysfunction in L929 cells. Subsequently, we found that autophagy inhibitors significantly delayed the senescence process, indicating that autophagy facilitated senescence. Moreover, ROS scavenger significantly decreased the autophagic level and improved mitochondrial function. Additionally, autophagy inhibitors effectively reduced ROS levels and ameliorated mitochondrial function. In conclusion, autophagy promoted senescence via enhancement of ROS generation and mitochondrial dysfunction in PAB-treated L929 cells.


At high temperature lipid production in Ettlia oleoabundans occurs before nitrate depletion.
Temperature and light intensity effects on biomass and lipid production were investigated in Ettlia oleoabundans to better understand some fundamental properties of this potentially useful but poorly studied microalgal species. E. oleoabundans entered dormant state at 5 °C, showed growth at 10 °C, and when exposed to light at 70 μmol photons per square meter per second at 10 °C, cells reached a biomass concentration of >2.0 g L(-1) with fatty acid methyl esters of 11.5 mg L(-1). Highest biomass productivity was at 15 °C and 25 °C regardless of light intensity, and accumulation of intracellular lipids was stimulated by nitrate depletion under these conditions. Although growth was inhibited at 35 °C, at 130 μmol photons per square meter per second lipid content reached 10.37 mg L(-1) with fatty acid content more favorable to biodiesel dominating; this occurred without nitrate depletion. In a two-phase temperature shift experiment at two nitrate levels, cells were shifted after 21 days at 15 °C to 35 °C for 8 days. Although after the shift growth continued, lipid productivity per cell was less than that in the 35 °C cultures, again without nitrate depletion. This study showed that E. oleoabundans grows well at low temperature and light intensity, and high temperature can be a useful trigger for lipid accumulation independent of nitrate depletion. This will prove useful for improving our knowledge about lipid production in this and other oleaginous algae for modifying yield and quality of algal lipids being considered for biodiesel production.


RNA sequences required for the noncoding function of oskar RNA also mediate regulation of Oskar protein expression by Bicoid Stability Factor.
The Drosophila oskar (osk) mRNA is unusual in having both coding and noncoding functions. As an mRNA, osk encodes a protein which is deployed specifically at the posterior of the oocyte. This spatially-restricted deployment relies on a program of mRNA localization and both repression and activation of translation, all dependent on regulatory elements located primarily in the 3' untranslated region (UTR) of the mRNA. The 3' UTR also mediates the noncoding function of osk, which is essential for progression through oogenesis. Mutations which most strongly disrupt the noncoding function are positioned in a short region (the C region) near the 3' end of the mRNA, in close proximity to elements required for activation of translation. We show that Bicoid Stability Factor (BSF) binds specifically to the C region of the mRNA. Both knockdown of bsf and mutation of BSF binding sites in osk mRNA have the same consequences: Osk expression is largely eliminated late in oogenesis, with both mRNA localization and translation disrupted. Although the C region of the osk 3' UTR is required for the noncoding function, BSF binding does not appear to be essential for that function.


BiMM tree: A decision tree method for modeling clustered and longitudinal binary outcomes.
Clustered binary outcomes are frequently encountered in clinical research (e.g. longitudinal studies). Generalized linear mixed models (GLMMs) for clustered endpoints have challenges for some scenarios (e.g. data with multi-way interactions and nonlinear predictors unknown a priori). We develop an alternative, data-driven method called Binary Mixed Model (BiMM) tree, which combines decision tree and GLMM within a unified framework. Simulation studies show that BiMM tree achieves slightly higher or similar accuracy compared to standard methods. The method is applied to a real dataset from the Acute Liver Failure Study Group.


Apoptotic Effect of Novel Benzimidazole Derivatives Bearing Pyridyl/Pyrimidinyl Piperazine Moiety.
Benzimidazole derivatives bearing pyridyl/pyrimidinyl piperazine moiety has attracted attention in medicinal chemistry and modern drug discovery since it exhibited a variety of biological activities, including anticancer activity. In this study, we designed and synthesized novel 1-[2-oxo-2-(4-substituted phenyl)ethyl]benzimidazol-2- yl)methyl 4-(2-pyridyl/pyrimidin-2-yl)piperazine-1-carbodithioate derivatives (2a-m). We also investigated their anticancer activities against A549 lung adenocarcinoma and C6 rat glioma cell lines. We further studied the selectivity of the compounds against the NIH/3T3 mouse embryonic fibroblast cell line. Cholinesterase inhibition effects of these compounds were also investigated to measure the relationship between anticancer activity and cholinesterases. The cytotoxic activities of these acquired thirteen final compounds were screened using MTT assay on A549, C6, and NIH/3T3 cell lines. Cell proliferation ELISA, BRDU (colorimetric) assay was used to measure the proliferation in replicative cells in which DNA synthesis occurs. Flow cytometric analysis was used to measure apoptotic cell percentages, caspase 3 activity, and mitochondrial membrane depolarised cell percentages. Compounds 2e, 2f, and 2k were shown to be the most active antitumor agents with selective cytotoxicities (the results for A549 were 76.58±6.43, 55.13±5.75, and 32.94±3.02 μM, respectively; and for C6 they were 86.48±3.60, 97.12±30.21, and 59.29±3.95 μM, respectively), high DNA synthesis inhibition rates and high apoptotic cell percentages on both cell lines. The results showed that compounds 2e, 2f, and 2k have potential anticancer activity against A549 and C6 cell lines.


[Closed reduction and pinning for acute slipped capital femoral epiphysis].
Acute slipped capital femoral epiphysis is a rare adolescent hip disorder, which may be a problem for orthopedic surgeon. No series to date has demonstrated the superiority of any treatment method. The purpose of the study was to evaluate the outcome of treatment and to assess the risk factors of avascular necrosis associated with this condition. Fourteen cases of acute slipped capital femoral epiphysis were treated with closed reduction and pinning. There were 9 boys and 5 girls. The average age at presentation was 11.8 years (range 9.1-15.3). Eight children were treated 4-10 days and six within 48 hours of the onset of their acute symptoms. The severity of the slip was classified according to the system of Southwick. Presence of chondrolysis and avascular necrosis was estimated. The clinical results were graded with the use of the criteria of Aadelen et al. Four slips were classified as mild, seven as moderate and three as severe. Average follow up was 5.2 years (range from 2.4 to 14.3). In two hips with severe slip AVN developed. One of these cases was treated within 48 hours and one after 7 days. Chondrolysis developed in one hip and was associated with presence of intra-articular fixation. Twelve of the fourteen hips had good and vary good results and remaining 2 with AVN had poor. Closed reduction and pinning in acute slipped capital femoral epiphysis is an effective and giving satisfactory outcome method of treatment. Early reduction is not associated with a high rate of AVN and should be performed as soon as possible. More severe slips were noted to have an increased risk of AVN.


Unraveling the mysteries of microwave chemistry using silicon carbide reactor technology.
In the past few years, the use of microwave energy to heat chemical reactions has become an increasingly popular theme in the scientific community. This nonclassical heating technique has slowly progressed from a laboratory curiosity to an established method commonly used both in academia and in industry. Because of its efficiency, microwave heating dramatically reduces reaction times (from days and hours to minutes and seconds) and improves product purities or material properties among other advantages. Since the early days of microwave chemistry, researchers have observed rate-accelerations and, in some cases, altered product distributions as compared with reactions carried out using classical oil-bath heating. As a result, researchers have speculated that so-called specific or nonthermal microwave effects could be responsible for these differences. Much of the debate has centered on the question of whether the electromagnetic field can exert a direct influence on a chemical transformation outside of the simple macroscopic change in bulk reaction temperature. In 2009, our group developed a relatively simple "trick" that allows us to rapidly evaluate whether an observed effect seen in a microwave-assisted reaction results from a purely thermal phenomenon, or involves specific or nonthermal microwave effects. We use a microwave reaction vessel made from silicon carbide (SiC) ceramic. Because of its high microwave absorptivity, the vessel shields its contents from the electromagnetic field. As a result, we can easily mimic a conventionally heated autoclave experiment inside a microwave reactor under carefully controlled reaction conditions. The switch from an almost microwave transparent glass (Pyrex) to a strongly microwave absorbing SiC reaction vial under otherwise identical reaction conditions (temperature profiles, pressure, stirring speed) then allows us to carefully evaluate the influence of the electromagnetic field on the particular chemical transformation. Over the past five years we have subjected a wide variety of chemical transformations, including organic reactions, preparations of inorganic nanoparticles, and the hydrolysis of proteins, to the "SiC test." In nearly all of the studied examples, we obtained identical results from reactions carried out in Pyrex vials and those carried out in SiC vials. The data obtained from these investigations confirm that in the overwhelming majority of cases a bulk temperature phenomenon drives the enhancements in microwave chemistry and that the electromagnetic field has no direct influence on the reaction pathway.


Phase behaviour and separation kinetics of polymer blends.
The liquid-liquid phase separation kinetics and phase behaviour of hydrogenated polyethylene and deuterated polypropylene blends have been systematically studied by optical microscope. Phase diagram was constructed from the phase transition temperature. The hydrogenated polyethylene/deuterated polypropylene blend exhibits upper critical solution temperature in the melt. The time evolution of the characteristics morphology for liquid-liquid phase separation is determined for the hydrogenated polyethylene/deuterated polypropylene blend at various compositions and following a quench from initial homogenous melts at higher temperature to various lower temperatures. Liquid-liquid phase separation kinetics follows nucleation and growth mechanism. The experimental results from optical microscope measurement at various conditions are all consistent with the nucleation and growth mechanism.


c-myc protein can be substituted for SV40 T antigen in SV40 DNA replication.
Replicating activity of SV40 origin-containing plasmid was tested in human cells as well as in monkey CosI cells. All the plasmids possessing SV40 ori sequences could replicate, even in the absence of SV40 T antigen, in human HL-60 and Raji cells which are expressing c-myc gene at high level. The copy numbers of the replicated plasmids in these human cells were 1/100 as high as in monkey CosI cells which express SV40 T antigen constitutively. Exactly the same plasmids as the transfected original ones were recovered from the Hirt supernatant of the transfected HL-60 cells. Furthermore, replication of the SV40 ori-containing plasmids in HL-60 cells was inhibited by anti-c-myc antibody co-transfected into the cells. These results indicate that the c-myc protein can be substituted for SV40 T antigen in SV40 DNA replication.


Conformational response of supercoiled DNA to confinement in a nanochannel.
Monte Carlo simulations were done to study the conformation of supercoiled DNA confined in a nanochannel. The molecule has a superhelical density of around -0.05 and is bathed in a monovalent salt solution with an ionic strength of 2, 10, or 150 mM. The cross-sectional diameter of the circular shaped nanochannel was varied in the range of 10 to 80 nm. The conformational properties were characterized by the writhing number and the distribution in the distance between the two opposing strands of the superhelix. With increasing confinement, as set by a smaller tube diameter and/or decreased screening of the Coulomb interaction, the supercoil becomes more tightly interwound and long-range structural features such as branching and the formation of hairpins are progressively suppressed. Analysis of the energetics shows a concurrent increase in electrostatic energy and energy of interaction of the supercoil with the wall, but the elastic twisting energy decreases. Confinement in a nanochannel or otherwise hence results in a decrease in the absolute value of the twist exerted on the duplex. The bending energy remains approximately constant, which means that there are no significant deflections from the wall. The simulation results are interpreted with theory based on the wormlike chain model, including the effects of the wall, charge, elasticity, and configurational entropy. It was found that the theory is reasonably successful in predicting the structural response to the confinement at the local level of the diameter and pitch of the supercoil.


Diagnostic effects of prolonged storage on fresh effusion samples.
The effects on morphology and diagnostic interpretation of delayed processing of refrigerated effusion samples have not been well documented. The potential for cellular degeneration has led many laboratories to reflexively fix samples rather than submit fresh/refrigerated samples for cytologic examination. We sought to determine if effusion specimens are suitable for morphologic, immunocytochemical, and DNA-based molecular studies after prolonged periods of refrigerated storage time. Ten fresh effusion specimens were refrigerated at 4 degrees C; aliquots were processed at specific points in time (days 0, 3, 5, 7, 10, 14). Specimens evaluated included four pleural (3 benign, 1 breast adenocarcinoma) and six peritoneal (2 ovarian adenocarcinomas, 1 malignant melanoma, 2 mesotheliomas, 1 atypical mesothelial) effusions. The morphology of the cytologic preparations from the 10 effusions was preserved and interpretable after 14 days of storage at 4 degrees C. The immunocytochemical profile of the samples (AE1/AE3, EMA, calretinin, and LCA) was consistent from day 0 to day 14. Amplifiable DNA was present in all samples tested on day 14. We conclude that cytopathologic interpretation of effusion samples remains reliable with refrigeration at 4 degrees C even if processing is delayed.


Vstx1, a modifier of Kv channel gating, localizes to the interfacial region of lipid bilayers.
VSTx1 is a tarantula venom toxin which binds to the archaebacterial voltage-gated potassium channel KvAP. VSTx1 is thought to access the voltage sensor domain of the channel via the lipid bilayer phase. In order to understand its mode of action and implications for the mechanism of channel activation, it is important to characterize the interactions of VSTx1 with lipid bilayers. Molecular dynamics (MD) simulations (for a total simulation time in excess of 0.2 micros) have been used to explore VSTx1 localization and interactions with zwitterionic (POPC) and with anionic (POPE/POPG) lipid bilayers. In particular, three series of MD simulations have been used to explore the net drift of VSTx1 relative to the center of a bilayer, starting from different locations of the toxin. The preferred location of the toxin is at the membrane/water interface. Although there are differences between POPC and POPE/POPG bilayers, in both cases the toxin forms favorable interactions at the interface, maximizing H-bonding to lipid headgroups and to water molecules while retaining interactions with the hydrophobic core of the bilayer. A 30 ns unrestrained simulation reveals dynamic partitioning of VSTx1 into the interface of a POPC bilayer. The preferential location of VSTx1 at the interface is discussed in the context of Kv channel gating models and provides support for a mode of action in which the toxin interacts with the Kv voltage sensor "paddle" formed by the S3 and S4 helices.


Is health-care delivery by partially trained professionals ever morally justified?
...teaching institutions should establish policies for all aspects of care provided by residents-in-training (not just for the acquisition of informed consent to treatment) and establish mechanisms to monitor how these policies are implemented and their effect on the quality of patient care and patient satisfaction with care. Clear policy on which treatments are provided by junior residents and which treatments and aspects of care are provided by senior residents is necessary for patients and their families to have control over what happens to them in the health-care institution.... Teaching institutions should regularly assess whether residents are being asked to take on more responsibilities in patient care than they are prepared to do. The reasons to do this are not solely related to protecting the patient from harm. Protecting the residents-in-training from overwhelming guilt, fear, and providing them with a more humane approach to medical education should be a minimal expectation for the training of those who will be expected to provide humane care to others....


[Immunologic determination of 3-hydroxyanthranilic acid in the blood of patients with tumors of the large intestine and rectum].
The results of study of an unusual antigen containing carcinogenic triptophan metabolite - 3-oxyanthranilic acid as a haptene (3-OAA-antigen) in blood serum of patients with colonic and rectal tumors indicated that it is present in the majority of patients with histologically proved cancer of the large intestine in different stages, as well as in some patients with polyps of the large intestine. 3-OAA-antigen is found to be absent in blood serum of healthy donors.


Recurrent idiopathic spontaneous coronary artery dissection.
Spontaneous coronary artery dissection (SCAD) is a relatively rare cause of acute coronary syndrome and sudden cardiac death, which frequently affect young women in the absence of established cardiovascular risk factors. Advancements in cardiovascular imaging account for the increasing recognition of this diagnosis and associated diagnoses, although classic diagnostic modalities such as electrocardiography remain of paramount importance. We present a young woman with recurrent SCAD and briefly discuss her management and its outcome.


Treatment compliance in adolescents after attempted suicide: a 2-year follow-up study.
To describe mental health services utilization for adolescents after attempted suicide, explore factors related to treatment compliance, and determine the relation between compliance and suicidality. Eighty-five adolescents (ages 13-18) who had attempted suicide and their families were recruited from four psychiatric hospitals and were evaluated for symptoms of psychopathology. Subsequent assessments were conducted every 6 months for 2 years to determine treatment utilization, treatment compliance (nonadherence to medication regimens or nonattendance of psychosocial treatments against provider advice), attitudes toward treatments used, and further suicide attempts and ideation. Adolescents with a disruptive behavior disorder diagnosis were less compliant with individual psychotherapy, as were those with a substance dependence other than alcohol or marijuana. Those with an affective/ anxiety disorder diagnosis were less compliant with psychopharmacological interventions (6 months postattempt). Parental perception of treatment as helpful was predictive of greater compliance, whereas adolescents' attitudes toward treatment were not predictive of compliance. Finally, compliance with treatment was not generally predictive of future suicidality. Interventions focused on increasing compliance with mental health treatment for adolescent suicide attempters should focus on specific child psychopathology, as well as parental attitudes toward treatment.


[Human muscle fatigue monitoring method and its application for exoskeleton interactive control].
Aiming at the human-computer interaction problem during the movement of the rehabilitation exoskeleton robot, this paper proposes an adaptive human-computer interaction control method based on real-time monitoring of human muscle state. Considering the efficiency of patient health monitoring and rehabilitation training, a new fatigue assessment algorithm was proposed. The method fully combined the human neuromuscular model, and used the relationship between the model parameter changes and the muscle state to achieve the classification of muscle fatigue state on the premise of ensuring the accuracy of the fatigue trend. In order to ensure the safety of human-computer interaction, a variable impedance control algorithm with this algorithm as the supervision link was proposed. On the basis of not adding redundant sensors, the evaluation algorithm was used as the perceptual decision-making link of the control system to monitor the muscle state in real time and carry out the robot control of fault-tolerant mechanism decision-making, so as to achieve the purpose of improving wearing comfort and improving the efficiency of rehabilitation training. Experiments show that the proposed human-computer interaction control method is effective and universal, and has broad application prospects.


Increasing ED Use of Jet Injection of Lidocaine for IV-Related Pain Management.
Venipuncture is a leading cause of procedural pain for children. Jet injection of lidocaine (JIL; J-Tip) has been demonstrated to be effective in controlling intravenous (IV) placement-related pain and, due to its rapid onset, is particularly suited to emergency department (ED) use. Our objective was to increase JIL use with IV placements in our ED from 11% at baseline to 50% within 12 months. We initiated the project at our urban, tertiary pediatric ED in July 2014. We surveyed medical and nursing teams to identify barriers to JIL use. We initiated changes at monthly intervals: (1) order set changes, (2) online education, (3) hands-on workshops, (4) improved accessibility, (5) standing order policy revision, and (6) reminders. We collected biweekly data on IV placements for all ED patients, except level 1 (critical) triage patients. We used standard quality improvement methodology and statistical process control for statistical analysis. JIL use with IV placement increased to 54% over 7 months and has remained >50% for >12 months. For all eligible IV placements (n = 12 791), 76.4% of those where JIL was used were successful on the first attempt compared with 75.8% without JIL (χ21degrees of freedom = 0.33, P = .56), with no significant difference in the success at IV placement. We sustainably increased JIL use with IV placement. The use of JIL was not associated with a difference in first-attempt IV placement success rates. We are expanding the project to other parts of the institution.


Portal vein thrombosis: etiology and clinical outcome of cirrhosis and malignancy-related non-cirrhotic, non-tumoral extrahepatic portal venous obstruction.
The etiology and pathogenesis of portal vein thrombosis are unclear. Portal venous thrombosis presentation differs in cirrhotic and tumor-related versus non-cirrhotic and non-tumoral extrahepatic portal venous obstruction (EHPVO). Non-cirrhotic and non-tumoral EHPVO patients are young and present with well tolerated bleeding. Cirrhosis and tumor-related portal vein thrombosis patients are older and have a grim prognosis. Among the 118 patients with portal vein thrombosis, 15.3% had cirrhosis, 42.4% had liver malignancy (primary or metastatic), 6% had pancreatitis (acute or chronic), 5% had hypercoagulable state and 31.3% had idiopathy, 12% had hypercoagulable state in the EHPVO group.


Accumulation of toxic metals and organic micro-pollutants in sediments from tropical urban rivers, Kinshasa, Democratic Republic of the Congo.
The increasing contamination of fresh water resource by toxic metals and Persistence Organic Pollutants (POPs) is a major environmental concern globally. In the present investigation, surface sediments collected from three main rivers named, Makelele, Kalamu and Nsanga, draining through the city of Kinshasa, Democratic Republic of the Congo, were characterized for grain size, organic matter, toxic metals, POPs (including organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs)), and polycyclic aromatic hydrocarbons (PAHs). Furthermore, enrichment factor (EF) and geoaccumulation index (Igeo) were performed to determine metal source and pollution status. The results highlighted high concentration of toxic metals in all sediment samples, reaching the values (mg kg-1) of 325 (Cu), 549 (Zn), 165 (Pb) and 1.5 (Cd). High values of PCBs and OCPs were detected in sediment samples, e.g. in Makelele river, PCB values ranged from 0.9 to 10.9 with total PCBs (∑7 PCBs × 4.3): 169.3 μg kg-1; OCPs from 21.6 to 146.8 with ∑OCPs: 270.6 μg kg-1. The PBDEs concentrations were higher in investigated rivers comparatively with values detected in many rivers from Sub-Saharan Africa. The ΣPAHs value ranged from 22.6 to 1011.9 μg kg-1. River contamination may be explained by local intense domestic activities, urban and agricultural runoff, industrial and hospital wastewaters discharge into the rivers without prior treatment. This research provides not only a first baseline information on the extent of contamination in this tropical ecosystem but also represents useful tools incorporated to evaluate sediment quality in the river receiving systems which can be applied to similar aquatic environments.


The effect of noradrenaline and acetylcholine on blood arginine vasotocin level in the domestic fowl.
The effect of naredrenaline and acetylcholine on the blood arginine vasotocin (AVT) level in hens as well as the effect of reserpine and atropine on the release of this hormone following the intravenous injection of hypertonic NaCl solution were investigated. It was dound that noradrenaline causes a decrease in blood AVT level in contrast to acetylcholine. Reserpine itself caused a rise in the blood AVT level; the effect was also found after administration of hypertonic solution. Atropine had no effect on the blood AVT level, but inhibited the AVT release following the adminstration of hypertonic Nacl solution.


Propagation velocities of chemical reaction fronts advected by Poiseuille flow.
Poiseuille flow between parallel plates advects chemical reaction fronts, distorting them and altering their propagation velocities. Analytical solutions of the cubic reaction-diffusion-advection equation resolve the chemical concentration for narrow gaps, wide gaps, and small-amplitude flow. Numerical solutions supply a general description for fluid flow in the direction of propagation of the chemical reaction front, and for flow in the opposite direction. Empirical relations for the velocity agree with numerical solutions to within a few percent, and agree exactly with the analytical limits. Applications to nonlinear fingering are discussed.


Quantum dynamics of a Bose superfluid vortex.
We derive a fully quantum-mechanical equation of motion for a vortex in a 2-dimensional Bose superfluid in the temperature regime where the normal fluid density ρ(n)(T) is small. The coupling between the vortex "zero mode" and the quasiparticles has no term linear in the quasiparticle variables--the lowest-order coupling is quadratic. We find that as a function of the dimensionless frequency Ω=ℏΩ/k(B)T, the standard Hall-Vinen-Iordanskii equations are valid when Ω≪1 (the "classical regime"), but elsewhere, the equations of motion become highly retarded, with significant experimental implications when Ω≳1.


Pharmacological actions of multi-target-directed evodiamine.
Evodiamine, a naturally occurring indole alkaloid, is one of the main bioactive ingredients of Evodiae fructus. With respect to the pharmacological actions of evodiamine, more attention has been paid to beneficial effects in insults involving cancer, obesity, nociception, inflammation, cardiovascular diseases, Alzheimer's disease, infectious diseases and thermo-regulative effects. Evodiamine has evolved a superior ability to bind various proteins, so we also argue that it is good starting point for multi-target drugs. This review is primarily addressed to the description of the recent advances in the biological activity studies of evodiamine, with a focus on pharmacological mechanism. The present review also includes the pharmacokinetics and the detailed exploration of target-binding properties of evodiamine in an attempt to provide a direction for further multi-target drug design.


Voiceless affricate/fricative distinction by frication duration and amplitude rise slope.
Previous psychophysical studies have shown that the perceptual distinction between voiceless fricatives and affricates in consonant-vowel syllables depends primarily on frication duration, whereas amplitude rise slope was suggested as the cue in automatic classification experiments. The effects of both cues on the manner of articulation between /integral of/ and /t integral of/ were investigated. Subjects performed a forced-choice task (/integral of/ or /t integral of) in response to edited waveforms of Japanese fricatives /integral of i/, /integral of u/, and /integral of a/. We found that frication duration, onset slope, and the interaction between duration and onset slope influenced the perceptual distinction. That is, the percent of /integral of/ responses increased with an increase in frication duration (experiments 1-3). The percent of /integral of/ responses also increased with a decrease in slope steepness (experiment 3), and the relative importance between slope portions was not even but weighted at onset (experiments 1 and 2). There was an interaction between the two cues of frication duration and steepness. The relative importance of the slope cue was maximum at a frication duration of 150 ms (experiment 3). It is concluded that the frication duration and amplitude rise slope at frication onset are acoustic cues that discriminate between /integral of/ and /t integral of/, and that the two cues interact with each other.


Critical role of exogenous nitric oxide in ROCK activity in vascular smooth muscle cells.
Rho-associated kinase (ROCK) signaling pathway has been shown to mediate various cellular functions including cell proliferation, migration, adhesion, apoptosis, and contraction, all of which may be involved in pathogenesis of atherosclerosis. Endogenous nitric oxide (NO) is well known to have an anti-atherosclerotic effect, whereas the exogenous NO-mediated cardiovascular effect still remains controversial. The purpose of this study was to evaluate the effect of exogenous NO on ROCK activity in vascular smooth muscle cells (VSMCs) in vitro and in vivo. VSMCs migration was evaluated using a modified Boyden chamber assay. ROCK activities were measured by Western blot analysis in murine and human VSMCs and aorta of mice treated with or without angiotensin II (Ang II) and/or sodium nitroprusside (SNP), an NO donor. Co-treatment with SNP inhibited the Ang II-induced cell migration and increases in ROCK activity in murine and human VSMCs. Similarly, the increased ROCK activity 2 weeks after Ang II infusion in the mouse aorta was substantially inhibited by subcutaneous injection of SNP. These findings suggest that administration of exogenous NO can inhibit ROCK activity in VSMCs in vitro and in vivo.


Phylogeographical Landscape of Citrobacter portucalensis Carrying Clinically Relevant Resistomes.
During a surveillance study conducted to assess the occurrence and genomic landscape of critical priority pathogens circulating at the human-animal-environment interface in Brazil, as part of the Grand Challenges Explorations-New Approaches to Characterize the Global Burden of Antimicrobial Resistance program, two multidrug-resistant (MDR) Citrobacter portucalensis carrying blaCTX-M-15 extended-spectrum β-lactamase (ESBL) genes, isolated from green sea turtles, were characterized. Genomic and phylogeographical analysis of C. portucalensis genomes available in public databases revealed the intercontinental dissemination of clades carrying different arrays of clinically relevant genes conferring resistance to carbapenems, broad-spectrum cephalosporins, cephamycins, aminoglycosides and fluoroquinolones, disinfectants, and heavy metals. Our observations suggest that C. portucalensis could be emerging as critical priority bacteria of both public and One Health importance worldwide. IMPORTANCE The global spread of antibiotic-resistant priority pathogens beyond the hospital setting is a critical issue within a One Health context that integrates the human-animal-environment interfaces. On the other hand, next-generation sequencing technologies along with user-friendly and high-quality bioinformatics tools have improved the identification of bacterial species, and bacterial resistance surveillance. The novel Citrobacter portucalensis species was proposed in 2017 after taxonomic reclassification and definition of the strain A60T isolated in 2008. Here, we presented genomic data showing the occurrence of multidrug-resistant C. portucalensis isolates carrying blaCTX-M-15 ESBL genes in South America. Additionally, we observed the intercontinental dissemination of clades harboring a broad resistome to clinically relevant antibiotics. Therefore, these findings highlight that C. portucalensis is a global MDR bacteria that carries intrinsic blaCMY- and qnrB-type genes and has become a critical priority pathogen due to the acquisition of clinically relevant resistance determinants, such as ESBL and carbapenemase-encoding genes.


Correcting for binomial measurement error in predictors in regression with application to analysis of DNA methylation rates by bisulfite sequencing.
Motivated by a genetic application, this paper addresses the problem of fitting regression models when the predictor is a proportion measured with error. While the problem of dealing with additive measurement error in fitting regression models has been extensively studied, the problem where the additive error is of a binomial nature has not been addressed. The measurement errors here are heteroscedastic for two reasons; dependence on the underlying true value and changing sampling effort over observations. While some of the previously developed methods for treating additive measurement error with heteroscedasticity can be used in this setting, other methods need modification. A new version of simulation extrapolation is developed, and we also explore a variation on the standard regression calibration method that uses a beta-binomial model based on the fact that the true value is a proportion. Although most of the methods introduced here can be used for fitting non-linear models, this paper will focus primarily on their use in fitting a linear model. While previous work has focused mainly on estimation of the coefficients, we will, with motivation from our example, also examine estimation of the variance around the regression line. In addressing these problems, we also discuss the appropriate manner in which to bootstrap for both inferences and bias assessment. The various methods are compared via simulation, and the results are illustrated using our motivating data, for which the goal is to relate the methylation rate of a blood sample to the age of the individual providing the sample. Copyright © 2016 John Wiley & Sons, Ltd.


Strategies to minimize readmission rates following major urologic surgery.
Readmissions after major surgical procedures are prevalent across multiple disciplines. Specifically, in urology, with incorporation of early discharge and recovery pathways, readmissions are emerging as an important problem and effecting an epidemic proportion of urology patients. As expected, readmissions have garnered the attention of major healthcare payers in the United States who see readmissions as easy targets because of the association with astronomical costs. More importantly, readmissions have a significant negative impact on patient sense of wellbeing, and places economic and other hardships on the doors of our patients and their families. Here, we explore the reasons patients are readmitted, using radical cystectomy as a case study, and means to decrease the incidence of readmissions. Since time to readmission for most major urologic oncology surgeries is within the first 2 weeks after discharge, this time frame is critical for efforts to improve symptom identification and reduce the total number and severity of readmissions. Readmission reduction to zero is unlikely for any major surgery, but with effective coordinated strategies, we must strive to reduce the rates as much as possible, as a means to improve the care continuum for our patients.


Fatty liver--an additional and treatable feature of the insulin resistance syndrome.
To test the hypothesis that fatty liver coexists with other metabolic abnormalities of the insulin resistance syndrome, and responds to their amelioration, we prospectively studied 48 consecutive patients with chronically elevated liver enzymes and clinical, ultrasound and histological findings consistent with fatty infiltration of the liver. Most of the patients were overweight or obese (64%) with increased waist circumference which closely relates to visceral fat. Only 10% of the patients had normal glucose tolerance: 44% had diabetes mellitus, 29% impaired glucose tolerance, and 17% were hyperinsulinaemic. The most common dyslipidaemia found was hypertriglyceridaemia and/or low HDL-C (86%). Dietary intervention and follow-up (median 24 months), supplemented by oral hypoglycaemic or lipid-lowering drugs as needed, resulted not only in weight loss (mean 3.7 kg), decreased fasting blood glucose (p < 0.005) and improvement in serum lipid profile (p < 0.02 for both triglycerides or HDL-C) but also in an improvement of serum liver enzymes in 96%, which became normal in more than half of the patients. Thus, fatty liver was strongly associated with many features of the insulin resistance syndrome, and follow-up revealed a high potential for reversibility and a benign course.


Vertical modeling: analysis of competing risks data with a cure fraction.
In this paper, we extend the vertical modeling approach for the analysis of survival data with competing risks to incorporate a cure fraction in the population, that is, a proportion of the population for which none of the competing events can occur. The proposed method has three components: the proportion of cure, the risk of failure, irrespective of the cause, and the relative risk of a certain cause of failure, given a failure occurred. Covariates may affect each of these components. An appealing aspect of the method is that it is a natural extension to competing risks of the semi-parametric mixture cure model in ordinary survival analysis; thus, causes of failure are assigned only if a failure occurs. This contrasts with the existing mixture cure model for competing risks of Larson and Dinse, which conditions at the onset on the future status presumably attained. Regression parameter estimates are obtained using an EM-algorithm. The performance of the estimators is evaluated in a simulation study. The method is illustrated using a melanoma cancer data set.