Levels of tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptors in chronic venous leg ulcers--correlations to healing status.
This study tested the hypothesis that excessive tumor necrosis factor-alpha (TNF-alpha) levels in chronic venous leg ulcers are associated with impaired healing. TNF-alpha was measured by two enzyme-linked immunosorbent assays and a bioassay (KYM-1D4) in paired wound fluid samples collected during the nonhealing and healing phases from 21 human patients with venous leg ulcers. Soluble TNF receptor levels (p55 and p75) were also measured. The levels of immunoreactive TNF-alpha were significantly higher in wound fluid from nonhealing ulcers than in wound fluid from healing ulcers (p < 0.005), whereas the levels of bioactive TNF-alpha were not. Statistical analysis confirmed that TNF-alpha bioactivity relative to the amount of immunoreactive TNF-alpha was downregulated in wound fluid from nonhealing ulcers compared with healing ulcers. The levels of soluble p55 and p75 receptors in wound fluid showed a significant linear correlation (p < 0.001), suggesting a partially coordinated or common regulatory mechanism for the cleavage of transmembrane TNF receptors in chronic venous ulcers in vivo. Although the levels of soluble p75 receptors were significantly higher in nonhealing wound fluid compared with healing wound fluid (p < 0.025), these levels were theoretically inadequate to substantially neutralize the bioactivity of the accompanying TNF-alpha levels on their own. The bioactivity accompanying the elevated levels of immunoreactive TNF-alpha in wound fluid from nonhealing ulcers may have been further down-modulated by an additional mechanism. Because healing was initiated without a significant decline in the level of bioactive TNF-alpha, TNF-alpha-mediated events may not be the key events contributing to the impaired healing seen in chronic venous ulcers.


Community-acquired in name only: A cluster of carbapenem-resistant Acinetobacter baumannii in a burn intensive care unit and beyond.
To describe an investigation into 5 clinical cases of carbapenem-resistant Acinetobacter baumannii (CRAB). Epidemiological investigation supplemented by whole-genome sequencing (WGS) of clinical and environmental isolates. A tertiary-care academic health center in Boston, Massachusetts. Individuals identified with CRAB clinical infections. A detailed review of patient demographic and clinical data was conducted. Clinical isolates underwent phenotypic antimicrobial susceptibility testing and WGS. Infection control practices were evaluated, and CRAB isolates obtained through environmental sampling were assessed by WGS. Genomic relatedness was measured by single-nucleotide polymorphism (SNP) analysis. Four clinical cases spanning 4 months were linked to a single index case; isolates differed by 1-7 SNPs and belonged to a single cluster. The index patient and 3 case patients were admitted to the same room prior to their development of CRAB infection, and 2 case patients were admitted to the same room within 48 hours of admission. A fourth case patient was admitted to a different unit. Environmental sampling identified highly contaminated areas, and WGS of 5 environmental isolates revealed that they were highly related to the clinical cluster. We report a cluster of highly resistant Acinetobacter baumannii that occurred in a burn ICU over 5 months and then spread to a separate ICU. Two case patients developed infections classified as community acquired under standard epidemiological definitions, but WGS revealed clonality, highlighting the risk of burn patients for early-onset nosocomial infections. An extensive investigation identified the role of environmental reservoirs.


Complete sequence of the duckweed (Lemna minor) chloroplast genome: structural organization and phylogenetic relationships to other angiosperms.
The complete nucleotide sequence of the duckweed (Lemna minor) chloroplast genome (cpDNA) was determined. The cpDNA is a circular molecule of 165,955 bp containing a pair of 31,223-bp inverted repeat regions (IRs), which are separated by small and large single-copy regions of 89,906 and 13,603 bp, respectively. The entire gene pool and relative positions of 112 genes (78 protein-encoding genes, 30 tRNA genes, and 4 rRNA genes) are almost identical to those of Amborella trichopoda cpDNA; the minor difference is the absence of infA and ycf15 genes in the duckweed cpDNA. The inverted repeat is expanded to include ycf1 and rps15 genes; this pattern is unique and does not occur in any other sequenced cpDNA of land plants. As in basal angiosperms and eudicots, but not in other monocots, the borders between IRs and a large single-copy region are located upstream of rps19 and downstream of trnH, so that trnH is not included in IRs. The model of rearrangements of the chloroplast genome during the evolution of monocots is proposed as the result of the comparison of cpDNA structures in duckweed and other monocots. The phylogenetic analyses of 61 protein-coding genes from 38 plastid genome sequences provided strong support for the monophyly of monocots and position of Lemna as the next diverging lineage of monocots after Acorales. Our analyses also provided support for Amborella as a sister to all other angiosperms, but in the bayesian phylogeny inference based on the first two codon positions Amborella united with Nymphaeales.


The Infant Born to a Woman with Gestational Diabetes.
Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset during pregnancy. During pregnancy, women with GDM develop insulin resistance, which results in altered glucose tolerance. As a result, there are frequent episodes of hyperglycemia and high levels of circulating amino acids, increasing the transfer of nutrients to the fetus. This article discusses the role of the mother-baby nursing in the care of neonates born to women with gestational diabetes.


Characterization of Long Linear and Branched Alkanes and Alcohols for Temperatures up to 573.15 K by Surface Light Scattering and Molecular Dynamics Simulations.
This work contributes to the characterization of long linear and branched alkanes and alcohols via the determination of their thermophysical properties up to temperatures of 573.15 K. For this, experimental techniques including surface light scattering (SLS) and molecular dynamics (MD) simulations were used under equilibrium conditions to analyze the influences of chain length, branching, and hydroxylation on liquid density, liquid viscosity, and surface tension. For probing these effects, 12 pure model systems given by the linear alkanes n-dodecane, n-hexadecane, n-octacosane, n-triacontane, and n-tetracontane, the linear alcohols 1-dodecanol, 1-hexadecanol, and 1,12-dodecanediol, the branched alkanes 2,2,4,4,6,8,8-heptamethylnonane (HMN) and 2,6,10,15,19,23-hexamethyltetracosane (squalane), and the branched alcohols 2-butyl-1-octanol and 2-hexyl-1-decanol were investigated at or close to saturation conditions at temperatures between 298.15 and 573.15 K. Based on the experimental results for the liquid densities, liquid viscosities, and surface tensions with average expanded uncertainties (k = 2) of 0.061, 2.1, and 2.6%, respectively, the performance of the three commonly employed force fields (FFs) TraPPE, MARTINI, and L-OPLS was assessed in MD simulations. To improve the simulation results for the best-performing all-atom L-OPLS FF at larger temperatures, a modified version was suggested. This incorporates a temperature dependence for the energy parameters of the Lennard-Jones potential obtained by calibrating only against the experimental liquid density data of n-dodecane. By transferring this approach to all other systems studied, the modified L-OPLS FF shows now a distinctly better representation of the equilibrium and transport properties of the long alkanes and alcohols, especially at high temperatures.


Plexin-Semaphorin Signaling Modifies Neuromuscular Defects in a Drosophila Model of Peripheral Neuropathy.
Dominant mutations in GARS, encoding the ubiquitous enzyme glycyl-tRNA synthetase (GlyRS), cause peripheral nerve degeneration and Charcot-Marie-Tooth disease type 2D (CMT2D). This genetic disorder exemplifies a recurring paradigm in neurodegeneration, in which mutations in essential genes cause selective degeneration of the nervous system. Recent evidence suggests that the mechanism underlying CMT2D involves extracellular neomorphic binding of mutant GlyRS to neuronally-expressed proteins. Consistent with this, our previous studies indicate a non-cell autonomous mechanism, whereby mutant GlyRS is secreted and interacts with the neuromuscular junction (NMJ). In this Drosophila model for CMT2D, we have previously shown that mutant gars expression decreases viability and larval motor function, and causes a concurrent build-up of mutant GlyRS at the larval neuromuscular presynapse. Here, we report additional phenotypes that closely mimic the axonal branching defects of Drosophila plexin transmembrane receptor mutants, implying interference of plexin signaling in gars mutants. Individual dosage reduction of two Drosophila Plexins, plexin A (plexA) and B (plexB) enhances and represses the viability and larval motor defects caused by mutant GlyRS, respectively. However, we find plexB levels, but not plexA levels, modify mutant GlyRS association with the presynaptic membrane. Furthermore, increasing availability of the plexB ligand, Semaphorin-2a (Sema2a), alleviates the pathology and the build-up of mutant GlyRS, suggesting competition for plexB binding may be occurring between these two ligands. This toxic gain-of-function and subversion of neurodevelopmental processes indicate that signaling pathways governing axonal guidance could be integral to neuropathology and may underlie the non-cell autonomous CMT2D mechanism.


[Neurofibromatosis Type 1: genetic studies with DNA markers in 38 families].
To establish preclinical DNA-diagnosis of neurofibromatosis type 1 (NF1) in familial cases we have investigated 38 families segregating for the disease. The families were tested with 6 polymorphic DNA markers from the chromosome region 17p11.1-q11.2. Two-thirds of the families were informative for flanking markers. An informative situation was achieved for 33 out of 40 individuals at risk (i.e. first degree relatives): 30 cases were diagnosed as noncarriers of the mutated gene, and three clinically normal individuals (including an adult and two children aged three and six respectively) were found to carry the risk haplotype. The remaining 7 persons at risk could not be typed unequivocally due to non-informative markers or recombination events. In 5 families with healthy grandparents the origin of the mutation could be traced back to the grandfather's germ cells. Despite the recent cloning and initial characterization of parts of NF1 gene, studies using linked and eventually intragenic DNA markers will continue to be of great value for genetic counselling. Such analyses allow highly accurate preclinical and prenatal diagnosis in close relatives of familial cases.


Effects of fluid management on edema volume and midline shift in a rat model of ischemic stroke.
The purpose of this study was to investigate the effects of fluid management on brain water content (BW) and midline shift (MLS) after a focal cerebral ischemic insult. A suture model was used to induce focal cerebral ischemia for 90 minutes (n=44). The rats were randomly assigned to 3 groups 2. 5 hours after reperfusion: dehydration (n=24), control (n=8), or hydration (n=12). BW was obtained with the wet-dry weight method 24 hours after middle cerebral artery (MCA) occlusion. In addition, MRI were obtained (n=31) 24 hours after the onset of ischemia so that the ratio of hemispheric volumes ipsilateral (IH) and contralateral (CH) to the infarct and the extent of MLS could be obtained. Across the range from moderate dehydration to intravascular volume expansion with isotonic saline, BW of the IH increased linearly as a function of change in body weight (r(2)=0.89), whereas few changes in relation to body weight were observed in CH, indicating a preferential effect of fluid management on the infarcted hemisphere. Furthermore, the hemispheric volume ratio (IH/CH) and MLS also increased in relation to changes in body weight. However, paradoxical increases in BW, IH/CH, and extent of MLS were observed in comparison with controls when severe dehydration was produced with high-dose mannitol. Changes in ischemic BW by fluid management correlated closely with changes in body weight except when high-dose mannitol was used. Mannitol, as a dehydrating agent, may be associated with bimodal effects, with a high dose aggravating ischemic BW.


Cannabinoid Receptor 1 and Fatty Acid Amide Hydrolase Contribute to Operant Sensation Seeking in Mice.
A large body of evidence in humans and preclinical models supports a role for the endocannabinoid system in the proper execution of motivated or goal-directed behaviors. Operant sensation seeking (OSS) is a task that uses varied sensory stimuli as a reinforcer to maintain operant responding in mice. The purpose of the studies in this report was to begin to explore the role of endocannabinoid signaling in OSS utilizing cannabinoid receptor 1 (CB1R) and fatty acid amide hydrolase (FAAH) knock out mice. Compared to wild type littermate controls, CB1R knock out mice exhibited significantly fewer active responses and earned significantly fewer reinforcers in fixed ratio and progressive ratio schedules. On the other hand, FAAH knock out mice exhibited increased active responses and earned more reinforcers than wild type littermates in fixed ratio but not progressive ratio schedules. These findings support the role of endocannabinoid signaling in motivated behaviors and also expand our understanding of the signaling processes involved in OSS.


Acute leg pain and weakness in pregnancy: A new diagnosis of myotonic dystrophy.
We present a unique case of a 44-year-old woman who presented at 29 weeks' gestation with proximal limb pain and elevated creatine kinase. This occurred in the background of premature cataracts, atrial fibrillation and abnormal liver function. Clinical, pathological and neurodiagnostic findings supported a diagnosis of myotonic dystrophy, confirmed by genetic testing which revealed dystrophia myotonica protein kinase gene expansion. Muscle biopsy found both recent necrotising and chronic myopathic processes. Following delivery, the mother's myalgia resolved and creatine kinase quickly declined. The fetus was diagnosed with congenital myotonic dystrophy. We review the impact of myotonic dystrophy on pregnancy and discuss potential explanations for this patient's clinical course. This case emphasises the importance of considering myotonic dystrophy as a differential diagnosis in the right clinical context and the need for pre-pregnancy assessment and genetic counselling in women with known myotonic dystrophy.


AHRA (American Healthcare Radiology Administrators) survey. Trends in radiology 1994: Part I.
Departments of medical imaging and therapy must balance the need to improve delivery and efficiency with the need to lower costs by finding better ways to deliver their services. As each department struggles to find its way, new trends will develop. In October, 1994, the AHRA surveyed its membership to determine those trends in hospital and nonhospital facilities. This article presents data and analysis for equipment acquisition and maintenance; operations; staffing and professional coverage; education programs; competition; marketing and new programs. Demographic information and comparisons with AHRA Trends Surveys conducted in 1985, 1987, 1989 and 1991 are included. Editor's Note: Part II of this article will review trends in exam volume, charges and volume from referral sources. Also, data from hospital departments will be analyzed by bed size groupings. Part II will be published in the summer, 1995, issue of Radiology Management, 17(3).


Chemokine networks in atopic dermatitis: traffic signals of disease.
Atopic dermatitis is a chronic or chronically relapsing inflammatory skin disease with a prevalence ranging from 10% to 20% in children and 1% to 3% in adults of developed countries. Skin-infiltrating leukocytes play a pivotal role in the initiation and amplification of atopic skin inflammation. Recent studies demonstrated that infiltration of inflammatory cells into tissues is regulated by chemokines. A subset of chemokines including CCL27, CCL17, CCL22, CCL18, CCL11, and CCL13 are highly expressed in atopic dermatitis. The corresponding chemokine receptors are found on the main leukocyte subsets involved in allergic skin inflammation, such as T cells, eosinophils, and dendritic cells. In this article, we provide an overview of the role of chemokines in the complex immunopathogenesis of atopic dermatitis, highlighting potential areas for therapeutic intervention.


Craving mediates the association between attentional bias to alcohol and in vivo alcoholic beverage consumption in young social drinkers.
Franken's attentional bias hypothesis proposes that attentional bias to alcohol (ABA) activates craving, which motivates alcohol consumption behavior. While this hypothesis was put forward to account for alcohol dependence, the present study tested whether Franken's model may potentially contribute to explaining variation in beer consumption among young social drinkers. ABA was measured by presenting participants with dual videos, one showing alcoholic beverages and the other non-alcoholic beverages, and assessing relative attention to each using a visual probe procedure. Self-reported alcohol craving was assessed four times over the session. In vivo alcoholic beverage consumption was assessed by the remaining weight of alcohol bottle following consumption, measured at conclusion of the experiment. The study revealed that ABA positively predicted alcohol craving (p < .01) and in vivo beer consumption (p < .01). The relationship between ABA and beer consumption was fully mediated by craving (β = .63, 95% CI [.04, 1.29]). To our knowledge, this is the first study to show that the relationship between ABA and in vivo alcoholic beverage consumption is fully mediated by alcohol craving. Future research can extend understanding of the causal relationship between ABA, craving, and consumption, by determining whether direct modification of ABA influences alcohol consumption by altering craving. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Effects of preoperative oral carbohydrate solution intake on thermoregulation.
We aimed to investigate the oral carbohydrate solution administered preoperatively on thermoregulation. The study included 40 female patients under general anesthesia. Patients were randomly divided into 2 groups: Group CONT (stopped oral implementation 8 h before the operation) and Group CHO (800ml oral carbohydrate fluid 8 h before the operation and 400ml oral carbohydrate fluid 2 h before the operation). Patients were monitored as standard and temperature probes were placed. Temperatures were recorded immediately before anesthetics induction, 5 min after the anesthetics induction, and in the post-anesthesia care unit (PACU) every 10 min. Mean skin temperature (Tsk), mean body temperature (Tb), and vasoconstriction threshold were estimated. In general, we observed a decrease in tympanic temperature and Tb following anesthetic administration in groups, and increase in Tsk, and an increase in all 3 of these levels in the recovery unit. Tympanic temperature was significantly higher at 25, 55, 65, and 95 min after induction in Group CONT compared to Group CHO (p<0.05). Tsk was found to be lower in Group CONT compared to Group CHO in almost all periods. In PACU, it was found that the tympanic temperature was higher in Group CONT compared to Group CHO at 60 min (p<0.05). Postoperative shivering score was found to be significantly higher in Group C (p<0.01). Vasoconstriction threshold was higher in Group CONT than Group CHO. Oral carbohydrate solution administered was established to have effects thought to be negative on tympanic temperature, vasoconstriction, and vasoconstriction threshold.


Cochlear implantation and change in quality of life.
The aim of this study was to assess the benefits of cochlear implantation (CI) in adults and to evaluate the average implant usage per day. Ten profoundly deaf adults were implanted during the period April 1994 to September 1997. The patients answered questionnaires 1 year or more after receiving their cochlear implants. All of the patients used their implant daily. The average implant usage per day was 16 h. The patients stated that, given the choice, they would again opt for a cochlear implant and would recommend a cochlear implant for a deaf friend. A paired comparison showed that the implants led to significant improvements in a number of factors: self-perceived communication skills, frequency of conversation with others, telephone usage, self-confidence and the impact of hearing impairments on family life. CI dramatically changed the quality of life for all patients. No surgical complications were observed.


KSHF Guidelines for the Management of Acute Heart Failure: Part II. Treatment of Acute Heart Failure.
The prevalence of heart failure (HF) is on the rise due to the aging of society. Furthermore, the continuous progress and widespread adoption of screening and diagnostic strategies have led to an increase in the detection rate of HF, effectively increasing the number of patients requiring monitoring and treatment. Because HF is associated with substantial rates of mortality and morbidity, as well as high socioeconomic burden, there is an increasing need for developing specific guidelines for HF management. The Korean guidelines for the diagnosis and management of chronic HF were introduced in March 2016. However, chronic and acute HF represent distinct disease entities. Here, we introduce the Korean guidelines for the management of acute HF with reduced or preserved ejection fraction. Part II of this guideline covers the treatment of acute HF.


[Functional echo morphology of Bauhin's valve].
Following rectal irrigation, it is possible to demonstrate the ileo-caecal valve sonographically, using a right para-inguinal approach. The shape, position and motility of the valve can be evaluated. The normal valve is two to three mm. thick, similar to the colonic wall, but its lips are thickened. Two distinct mechanisms are responsible for opening the valve, the ileocolic pressure gradient and relaxation of the circular muscle round the valve. The resulting intraluminal flow can be quantified by duplex sonography. The information may be of diagnostic and therapeutic significance, particularly during childhood.


Involvement of Nrf2 and JNK1 in the activation of antioxidant responsive element (ARE) by chemopreventive agent phenethyl isothiocyanate (PEITC).
Phenethyl isothiocyanate (PEITC) has been of great interest as a promising cancer chemopreventive agent. To better understand its chemopreventive activity, we examined the effect of PEITC on the antioxidant responsive element (ARE), which is an important gene regulatory element of many phase II drug-metabolizing/detoxification enzymes as well as cellular defensive enzymes. HeLa cells were transiently transfected with different cDNA plasmids using calcium phosphate precipitation. Subsequently, the cells were maintained in fresh media, and various concentrations of PEITC were added to the transfected cells. After harvesting and lysing of the cells, ARE-luciferase reporter gene activity was measured and normalized against beta-galactosidase activity. Treatments of HeLa cells with PEITC transiently stimulated ARE-reporter gene expressions in a dose-dependent manner. Overexpression of wild-type NF-E2 related factor-2 (Nrf2) dramatically increased ARE-reporter gene expression in a dose-dependent manner. Similar effects were seen when wild-type c-Jun N-terminal kinase 1 (JNK1) was transfected, although the transactivating potential of JNK1 was much less than that of Nrf2. Cotransfection of Nrf2 and JNK1 showed additional enhancement of ARE reporter gene expression, implying that JNK1 might be an upstream activator of Nrf2. To support this, overexpression of dominant-negative JNK1 suppressed Nrf2-induced ARE reporter gene expression in a dose-dependent manner. When PEITC was added, slight enhancement of ARE reporter gene expression was observed in either Nrf2- or JNK1-transfected cells. Finally, ARE reporter activity induced by PEITC was substantially attenuated by transfection of either dominant-negative mutant of Nrf2 or dominant-negative mutant of JNK1. Taken together, these data suggest that JNK1 acts as an upstream activator of Nrf2 and that PEITC activates ARE-mediated phase II drug metabolism gene expressions via the JNK1- and Nrf2-dependent pathways.


Sildenafil Decreases BACE1 and Cathepsin B Levels and Reduces APP Amyloidogenic Processing in the SAMP8 Mouse.
The senescence-accelerated mouse-prone 8 (SAMP8), used as a model of aging, displays many established pathological features of Alzheimer's disease. Cognitive impairments and increased levels of hyperphosphorylated tau are found in the hippocampus of SAMP8 mice along with an increased β-secretase activity and amyloid-β (Aβ) depositions that increase in number and extent with age. Based on a previous study from our laboratory showing an amelioration of cognitive impairments and tau pathology by sildenafil, in this study we tested whether this drug could also modulate the amyloid precursor protein amyloidogenic processing in this mouse model. Our results show that the protein levels of the β-secretases β-site amyloid precursor protein cleaving enzyme 1 and cathepsin B are higher in the hippocampus of 9-month-old SAMP8 mice than those of age-matched senescence-resistant-1. Sildenafil (7.5mg/kg for 4 weeks) attenuated learning and memory impairments shown by SAMP8 mice in the passive avoidance test. The increased expression of β-site amyloid precursor protein cleaving enzyme 1 was also reduced by sildenafil, an effect paralleled to decreases in the activities of two β-site amyloid precursor protein cleaving enzyme 1 modulators, calpain and cyclin-dependent kinase 5 protein. Interestingly, sildenafil enhanced both Akt and glycogen synthase kinase-3β (ser9) phosphorylation, which could be mediating the reduction in cathepsin B levels found in the hippocampus of sildenafil-treated SAMP8 mice. Sildenafil-induced reduction in β-site amyloid precursor protein cleaving enzyme 1 and cathepsin B expression in SAMP8 mice was associated with a decrease in hippocampal Aβ42 levels which, in turn, could mediate the parallel decline in glial fibrillary acidic protein expression observed in these animals. These findings highlight the therapeutic potential of sildenafil in Alzheimer's disease pathogenesis.


A phase I/II trial of etoposide and cisplatin in extensive small cell lung cancer: a cancer and leukemia group B study.
Patients with untreated extensive small cell lung cancer (SCLC) with CALGB performance scores 0-2 were treated with etoposide 200 mg/m2/day on days 1-3 and cisplatin doses of 20, 30, or 35 mg/m2/day days 1-3 in a Phase I/II format. Of the nine patients treated at the 35 mg/m2/day cisplatin dose in the Phase I portion of the study, Grade 4 leukopenia occurred in five patients and Grade 4 thrombocytopenia in four. There were two deaths due to myelosuppression and sepsis. This dose was thus considered the maximum tolerated dose (MTD), and a Phase II trial was then conducted using this treatment program. In the Phase II trial of 39 patients, the objective response rate was 67% (95% confidence interval, 50-81%) with 21% complete responses (CI 9-36%). Median survival was 10.5 months. Grade 4-5 leukopenia was seen in 57% and Grade 4-5 thrombocytopenia in 56%. The MTD defined by this Phase I trial represents a 67-100% increase in etoposide and a 32-42% increase in cisplatin dosage compared to prior studies. The observed objective response rates with this regimen are comparable to studies using conventional doses, but hematological toxicity was higher.


Cohnella xylanilytica sp. nov. and Cohnella terrae sp. nov., xylanolytic bacteria from soil.
Two xylan-degrading bacteria, strains MX15-2(T) and MX21-2(T), were isolated from soils collected in Nan province, Thailand. Cells were Gram-reaction-positive, facultatively anaerobic, spore-forming and rod-shaped. They contained meso-diaminopimelic acid in the cell-wall peptidoglycan. The major menaquinone was MK-7. iso-C(16 : 0) and anteiso-C(15 : 0) were the predominant cellular fatty acids. Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and lysyl-phosphatidylglycerol were the major polar lipids. The genomic DNA G+C contents of strains MX15-2(T) and MX21-2(T) were 63.0 and 65.1 mol%, respectively. Phylogenetic analysis using 16S rRNA gene sequences showed that strains MX15-2(T) and MX21-2(T) were affiliated with the genus Cohnella and were closely related to Cohnella thermotolerans CCUG 47242(T), with 96.5 and 95.6 % sequence similarity, respectively. The strains could be clearly distinguished from each other and from all known species of the genus Cohnella based on their physiological and biochemical characteristics as well as their phylogenetic positions and levels of DNA-DNA hybridization. Therefore, these two strains represent novel species of the genus Cohnella, for which the names Cohnella xylanilytica sp. nov. (type strain MX15-2(T) =KCTC 22294(T) =PCU 309(T) =TISTR 1891(T)) and Cohnella terrae sp. nov. (type strain MX21-2(T) =KCTC 22295(T) =PCU 310(T) =TISTR 1892(T)) are proposed.


Obstructive Sleep Apnea, Other Sleep Characteristics, and Risk of CKD in the Atherosclerosis Risk in Communities Sleep Heart Health Study.
Obstructive sleep apnea may be associated with development of CKD through hypoxia, inflammation, and oxidative stress. Individuals with this sleep disorder are also at increased risk for established CKD risk factors, including obesity, hypertension, and type 2 diabetes. We examined the association between obstructive sleep apnea, other sleep characteristics, and risk of incident CKD (stage 3 or higher) in 1525 participants (mean age, 62.5 years; 52.4% women) in the Atherosclerosis Risk in Communities (ARIC) study who completed in-home polysomnography assessments. We used the apnea-hypopnea index (events per hour) to define obstructive sleep apnea severity (normal, <5.0; mild, 5.0-14.9; moderate, 15.0-29.9; and severe, ≥30.0) and defined incident CKD (stage 3 or higher) as eGFR<60 ml/min per 1.73 m2 and ≥25% decline from baseline, CKD-related hospitalization or death, or ESKD. Cox proportional hazards regression was used to estimate obstructive sleep apnea severity with risk of incident CKD, adjusting for demographics, lifestyle behaviors, and cardiometabolic conditions. During 19 years (median) of follow-up, 461 CKD events occurred. After adjustment for demographics and lifestyle behaviors, severe obstructive sleep apnea associated with increased risk of CKD (hazard ratio [HR], 1.51; 95% confidence interval [95% CI], 1.08 to 2.10), which was attenuated after adjustment for body mass index (HR, 1.07; 95% CI, 0.75 to 1.52). No other sleep characteristics associated with incident CKD. We found a link between obstructive sleep apnea and an elevated risk of stage 3 CKD or higher, but this association was no longer significant after adjusting for obesity, a risk factor for both conditions. Given the high prevalence of obstructive sleep apnea and CKD among adults, further investigation is warranted.


Chemerin analog regulates energy metabolism in sheep.
Accumulating data suggest a relationship between chemerin and energy metabolism. Our group previously described gene cloning, expression analysis and the regulatory mechanism of chemerin and its own receptor in mice and cattle. The objective of the present study was to investigate the physiological effect of chemerin on endocrine changes and energy metabolism in sheep using a biologically stable chemerin analog. The chemerin analog was intravenously administrated (100 or 500 µg/head) to sheep, and plasma insulin and metabolites (glucose, nonesterified fatty acids (NEFA), triglyceride, total cholesterol and high-density lipoprotein (HDL) cholesterol) were analyzed. The chemerin analog dramatically increased the insulin levels, and glucose levels were decreased. NEFA levels were slightly decreased at 20 min but then increased gradually from 60 to 180 min after analog administration. In addition, injection of the chemerin analog immediately increased triglyceride and total cholesterol but not HDL levels. These results suggested that chemerin analog regulated insulin secretion related to glucose metabolism and the release of triglycerides in sheep in vivo. This study provides new information about endocrine and metabolic changes in response to chemerin in sheep.


["The honor of being right": Experiment and theory in the dispute over the doctrine of irritability].
In the middle of the 18th century the leading physiological concepts shift from mechanism to vitalism. The turning point of this change is Albrecht von Haller's Dissertation on the irritable parts (1752/53). The decisive discussion about irritability takes place between strictly empirical Hallerians and their opponents who try to build new medical systems on this property. Hence, the debate is also about experiment and theory. The 'sociology of scientific knowledge' furnishes models and theories that help us to conceive the argumentations and strategies of the leading figures. Thus, we understand why even Haller--the 'founder of modern experimental physiology'--has to allow general conclusions and to support vitalistic interpretations if he wants to succeed with some of his views. Only in its modified form the 'Irritabilitas Halleriana' meets the interest needed for dissemination.


Kinetic and thermodynamic studies of 9-aminocamptothecin hydrolysis at physiological pH in the presence of human serum albumin.
As a first step towards improving the aqueous stability of 9-aminocamptothecin (9AC), a detailed kinetic and thermodynamic investigation of the hydrolysis reaction of 9AC was carried out, using a first derivative absorption spectrophotometry technique. It was found that 9AC-lactone decayed with a half-life of 25 min in PBS at pH 7.4 and 310.15K. The activation energy (Ea) associated with the hydrolysis of 9AC-lactone was 87.3 ± 3.8 kJmol(-1), whereas the positive enthalpy and entropy values of the 9AC-lactone hydrolysis reaction indicated that the reaction is endothermic and entropically driven. Similarly to other camptothecin analogs, except for SN38, the activation energy for 9AC-lactone hydrolysis in the presence of Human Serum Albumin (HSA) was about 10 kJmol(-1) lower than that determined in plain PBS, whereas the equilibrium 9AC-lactone concentration was decreased in the presence of HSA as compared to that in plain PBS. The lower Ea for 9AC hydrolysis in presence of HSA fully explained the shift of lactone-carboxylate equilibrium towards the carboxylate form with only 4% of active 9AC-lactone remaining in the presence of HSA under physiological conditions. Finally, affinity studies of several camptothecin analogs with HSA, showed that the association constants of the lactone species with HSA are similar and pointed out that the superior stability of the SN38 over the other two analogs (9AC and 9-nitrocamptothecin) is not due to the higher affinity of lactone toward HSA, but it is rather due to the lower affinity of the SN38-carboxylate toward HSA.


[Age-related changes of the epidermis of men's scalp].
Histological, morphometric and immunocytochemical methods were used to study the autopsy samples of the interfollicular epidermis in the temporal region of scalp of male individuals aged from 7 months to 75 years. Monoclonal antibodies against Ki-67, involucrin and p53 were applied to evaluate the proliferative pool in the epidermis, the thickness of the layer of the cells which started the terminal differentiation, and the fraction of the apoptotic cells. Epidermis in children was thin; it had a low content of Ki-67- and p53-positive cells and small thickness of involucrin-positive cell layer. The highest proliferative activity and maximal thickness of the epidermis were detected at the age of 19-21 years. Thereafter the epidermis thinning was observed, together with the progressive decrease of keratinocyte proliferative activity and an increase of the fraction of p53-positive cells. Absolute thickness of the involucrin-positive cellular layer remained practically constant at different ages, while its proportion in the total epidermal thickness uncreased.


Loss of secondary esophageal peristalsis is not a contributory pathogenetic factor in posterior laryngitis.
Secondary esophageal peristalsis helps prevent the entry of gastric acid into the pharynx by clearing the refluxed gastric contents back into the stomach. Because the loss of this mechanism may contribute to the pathogenesis of reflux-induced laryngeal disorders, our aim was to study the frequency of stimulation and parameters of secondary esophageal peristalsis in patients with posterior laryngitis (PL). We studied 14 patients (45 +/- 5 years) with PL documented by videolaryngoscopy and 11 healthy controls (46 +/- 6 years). The upper esophageal sphincter (UES) pressure was monitored by a sleeve assembly incorporating an injection port 5 cm distal to the sleeve. The esophageal body and lower esophageal sphincter (LES) pressures were measured by an LES sleeve assembly. Primary esophageal peristalsis was induced by 5-mL water swallows. Secondary esophageal peristalsis was induced by abrupt injection of volumes of air, incrementally increased by 5 mL, into the esophagus. Secondary esophageal peristalsis could not be elicited by injection of any volume (up to 60 mL) in 3 PL patients and 2 controls. These 5 subjects had normal primary peristalsis. The threshold volume of air required to stimulate secondary esophageal peristalsis in PL patients (median, 15 mL) was similar to that of controls (median, 10 mL). The parameters of the secondary esophageal peristaltic pressure wave were similar in both groups, and in both groups, they were similar to those of primary peristalsis. The UES response to the injection of the threshold volume that induced secondary esophageal peristalsis in PL patients was contraction in 58% of the trials, partial relaxation in 3%, and no response in 39%. The findings were similar to those in the controls. The LES response to injection of the threshold volume was complete relaxation in both the PL patients and the controls. We conclude that the integrity of secondary esophageal peristalsis is preserved in PL patients.


[Early enteral nutrition and immunonutrition].
The repercussions of nutrition on the immunological system are described. The current situation is discussed with regard to the handling of the immuno-inflammatory response to aggression and the improvement of the immune response. The goal pursued by nutritional manipulation of the immune system is to improve the prognosis and reduce the complications in critical patients subjected to surgical or traumatic aggression or sepsis. The following points are reviewed: the importance of preserving the axis from the liver to the digestive tract, the advantages of particularly early enteral nutrition over parenteral nutrition, the substances currently considered as immunonutrients and the available clinical evidence on their use, with a series of conclusions for current decisions and future developments.


The ability of cytotoxic T cells to recognize HLA-A2.1 or HLA-B7 antigens expressed on murine cells correlates with their epitope specificity.
Two groups of human and murine cytotoxic T lymphocyte (CTL) clones specific for human leukocyte antigen (HLA)-A2 or -B7 can be distinguished based on their ability to kill murine transfectants expressing these molecules. The clones which do not recognize murine transfectants exhibited greatly reduced conjugate formation with these cells, indicating that the inability to lyse these cells occurs in recognition and binding. No systematic differences in inhibitory titer between the two types of CTL clones were seen with anti-CD8 (Lyt-2), anti-LFA-1, or monoclonal antibodies against HLA class I molecules. However, blocking with anti-HLA class I monoclonal antibodies suggested that different CTL clones recognized spatially separate epitopes on HLA-A2 and -B7. In addition, a correlation between the inability to recognize murine transfectants and fine specificity was seen. Eight of nine clones which did not lyse murine transfectants also failed to recognize human cells expressing HLA-A2.2 or -A2.3. In contrast only 5 of 12 clones which lysed transfectants failed to recognize the variant molecules. Analogous data were obtained with human CTL clones raised against HLA-A2.1. These findings suggest that CTL clones that do not lyse murine cells expressing appropriate antigens recognize epitopes that have been altered or lost as a consequence of expression on the murine cell surface. It is suggested that the loss of HLA-associated epitopes on the murine cell surface may be due to differences between mouse and human cells in the processing or presentation of class I-associated peptides.


Weight Loss in Obese Patients With Heart Failure.
In heart failure (HF), weight loss (WL) has been associated with an adverse prognosis whereas obesity has been linked to lower mortality (the obesity paradox). The impact of WL in obese patients with HF is incompletely understood. Our objective was to explore the prevalence of WL and its impact on long-term mortality, with an emphasis on obese patients, in a cohort of patients with chronic HF. Weight at first visit and the 1-year follow-up and vital status after 3 years were assessed in 1000 consecutive ambulatory, chronic HF patients (72.7% men; mean age 65.8±12.1 years). Significant WL was defined as a loss of ≥5% weight between baseline and 1 year. Obesity was defined as body mass index ≥30 kg/m(2) (N=272). Of the 1000 patients included, 170 experienced significant WL during the first year of follow-up. Mortality was significantly higher in patients with significant WL (27.6% versus 15.3%, P<0.001). In univariable Cox regression analysis, patients with significant WL had 2-fold higher mortality (hazard ratio 1.95 [95% CI 1.39-2.72], P<0.001). In multivariable analysis, adjusting for age, sex, body mass index, New York Heart Association functional class, left ventricular ejection fraction, HF duration, ischemic etiology, diabetes, and treatment, significant WL remained independently associated with higher mortality (hazard ratio 1.89 [95% CI 1.32-2.68], P<0.001). Among obese patients with HF, significant WL was associated with an even more ominous prognosis (adjusted hazard ratio for death of 2.38 [95% CI 1.31-4.32], P=0.004) than that observed in nonobese patients (adjusted hazard ratio 1.83 [95% CI 1.16-2.89], P=0.01). Weight loss ≥5% in patients with chronic HF was associated with high long-term mortality, particularly among obese patients with HF.


Efficiency of visual feedback integration differs between dominant and non-dominant arms during a reaching task.
Recent studies have shown that patterns of endpoint variability following double-step reach sequences reflect the influence of both planning and execution-related processes, but are strongly dominated by noise associated with the online updating of movement plans based on visual feedback. However, it is currently unclear whether these results reflect the dominant arm/hemisphere's postulated specialization for visual feedback processing, or whether these effects reflect a more general "arm/hemisphere independent" preference for visual feedback in the control of reaching. To explore this, twelve subjects performed double-step reach sequences with their dominant and non-dominant arms to targets in 3D space with and without visual feedback of the arm. Variability was quantified using the volumes, aspect ratios, and orientations of 95% confidence ellipsoids fit to the distributions of reach endpoints. In consonance with previous findings, the availability of visual feedback resulted in ellipsoids that were significantly smaller, had greater aspect ratios, and were more aligned with the depth axis than those performed without visual feedback. Moreover, the effects of vision on aspect ratio and orientation were similar in magnitude for the dominant and non-dominant arms, suggesting that noise associated with planning and execution-related processes is managed in a similar way by the sensorimotor systems of each arm. However, the degree to which vision decreased ellipsoid volume was found to be significantly greater for the dominant arm. This suggests that the feedback control system of the dominant arm uses visual information more efficiently to control reaches to visual targets.


Sequential changes in plasma renin activity and aldosterone level during pregnancy.
Sequential changes in plasma renin activity (PRA) and the plasma aldosterone (PA) level were studied prospectively in 101 patients at Taipei Municipal Women and Children Hospital from the 20th week of gestation to the 4th week postpartum. Average maternal age was 31.8 years old and average fetal birth weight was 3,235 g. The PRA and PA levels during pregnancy were higher than those of the normal nonpregnant women. PRA decreased gradually from the 20th week of gestation and dropped markedly after delivery. The PA level increased after the 20th week of gestation and peaked at the 32nd gestational week, then returned to the nonpregnancy level after delivery. A dissociation between the PRA and PA levels after the 28th week of gestation was observed. Possible causes for this dissociation are discussed. This study provides reference data on PA and PRA levels during the course of a normal pregnancy for use in further studies on abnormal gestation.


Innate immunity but not NLRP3 inflammasome activation correlates with severity of stable COPD.
In models of COPD, environmental stressors induce innate immune responses, inflammasome activation and inflammation. However, the interaction between these responses and their role in driving pulmonary inflammation in stable COPD is unknown. To investigate the activation of innate immunity and inflammasome pathways in the bronchial mucosa and bronchoalveolar lavage (BAL) of patients with stable COPD of different severity and control healthy smokers and non-smokers. Innate immune mediators (interleukin (IL)-6, IL-7, IL-10, IL-27, IL-37, thymic stromal lymphopoietin (TSLP), interferon γ and their receptors, STAT1 and pSTAT1) and inflammasome components (NLRP3, NALP7, caspase 1, IL-1β and its receptors, IL-18, IL-33, ST2) were measured in the bronchial mucosa using immunohistochemistry. IL-6, soluble IL-6R, sgp130, IL-7, IL-27, HMGB1, IL-33, IL-37 and soluble ST2 were measured in BAL using ELISA. In bronchial biopsies IL-27+ and pSTAT1+ cells are increased in patients with severe COPD compared with control healthy smokers. IL-7+ cells are increased in patients with COPD and control smokers compared with control non-smokers. In severe stable COPD IL-7R+, IL-27R+ and TSLPR+ cells are increased in comparison with both control groups. The NALP3 inflammasome is not activated in patients with stable COPD compared with control subjects. The inflammasome inhibitory molecules NALP7 and IL-37 are increased in patients with COPD compared with control smokers. IL-6 levels are increased in BAL from patients with stable COPD compared with control smokers with normal lung function whereas IL-1β and IL-18 were similar across all groups. Increased expression of IL-27, IL-37 and NALP7 in the bronchial mucosa may be involved in progression of stable COPD.


[Morphometric analysis of the state of the intraorganic blood vessels].
A method for reconstruction of intraorganic vessels sections visible in histological sections into the sections of regular round vessels with preservation of real area of their wall and lumen is presented. A new characteristic of the vessel state is introduced -- degree of elastic membrane twistiness. Changes in various branches of the dog pulmonary artery at burns and at simultaneous bilateral resection of 58% lung tissue are taken as an example in order to demonstrate that at a complex analysis of the vascular wall area/the lumen area ratio, taking into account the degree of elastic membrane twistiness, it is possible to differentiate functional changes of the vascular tonus from the organic ones.


Six-month results from a Phase III randomized trial of fixed-combination brinzolamide 1% + brimonidine 0.2% versus brinzolamide or brimonidine monotherapy in glaucoma or ocular hypertension.
The objective of this study was to examine the safety and intraocular pressure (IOP)-lowering efficacy of a fixed combination of brinzolamide 1% + brimonidine 0.2% (BBFC) after six months of treatment in patients with open-angle glaucoma or ocular hypertension. This was a randomized, multicenter, double-masked, three-month, three-arm contribution-of-elements study with a three-month safety extension. Patients were randomly assigned 1:1:1 to treatment with BBFC, brinzolamide 1%, or brimonidine 0.2% after a washout period. Patients dosed their study medications three times daily at 8 am, 3 pm, and 10 pm for six months. Patients returned for visits at two weeks, six weeks, three months, and six months. IOP measurements were used to assess efficacy. Safety assessments were adverse events, corrected distance visual acuity, slit-lamp biomicroscopy, pachymetry, perimetry, fundus parameters, and cardiac parameters. A total of 690 patients were randomized. Six-month mean IOP values were similar to those at three months, when the mean IOP in patients treated with BBFC was significantly lower than that of either monotherapy group. A total of 175 patients experienced at least one treatment-related adverse event (BBFC, 33.0%; brinzolamide, 18.8%; brimonidine, 24.7%), eight of which were severe, and five resulted in discontinuation. Seventy-seven patients discontinued participation due to treatment-related adverse events (BBFC, 17.2%; brinzolamide, 2.1%; brimonidine, 14.5%). There were 21 serious adverse events (n = 7 in each group), none of which was related to treatment. Resting mean pulse and blood pressure with BBFC were similar to those with brimonidine, demonstrating modest, clinically insignificant decreases. No new or increased risks were identified with use of BBFC relative to either monotherapy. This study showed that, after six months of treatment, the safety profile of BBFC was similar to that of its individual components and its IOP-lowering activity was similar to its efficacy at three months, when it was superior to both brinzolamide 1% alone and brimonidine 0.2% alone.


Atmospheric-pressure ionization and fragmentation of peptides by solution-cathode glow discharge.
Modern "-omics" (e.g., proteomics, glycomics, metabolomics, etc.) analyses rely heavily on electrospray ionization and tandem mass spectrometry to determine the structural identity of target species. Unfortunately, these methods are limited to specialized mass spectrometry instrumentation. Here, a novel approach is described that enables ionization and controlled, tunable fragmentation of peptides at atmospheric pressure. In the new source, a direct-current plasma is sustained between a tapered metal rod and a flowing sample-containing solution. As the liquid stream contacts the electrical discharge, peptides from the solution are volatilized, ionized, and fragmented. At high discharge currents (e.g., 70 mA), electrospray-like spectra are observed, dominated by singly and doubly protonated molecular ions. At lower currents (35 mA), many peptides exhibit extensive fragmentation, with a-, b-, c-, x-, and y-type ion series present as well as complex fragments, such as d-type ions, not previously observed with atmospheric-pressure dissociation. Though the mechanism of fragmentation is currently unclear, observations indicate it could result from the interaction of peptides with gas-phase radicals or ultraviolet radiation generated within the plasma.


Prior Stroke in PFO Patients Is Associated With Both PFO-Related and -Unrelated Factors.
Background and Purpose: To identify factors associated with prior stroke at presentation in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO). Methods: We studied cross-sectional data from the International PFO Consortium Study (NCT00859885). Patients with first-ever stroke and those with prior stroke at baseline were analyzed for an association with PFO-related (right-to-left shunt at rest, atrial septal aneurysm, deep venous thrombosis, pulmonary embolism, and Valsalva maneuver) and PFO-unrelated factors (age, gender, BMI, hypertension, diabetes mellitus, hypercholesterolemia, smoking, migraine, coronary artery disease, aortic plaque). A multivariable analysis was used to adjust effect estimation for confounding, e.g., owing to the age-dependent definition of study groups in this cross-sectional study design. Results: We identified 635 patients with first-ever and 53 patients with prior stroke. Age, BMI, hypertension, diabetes mellitus, hypercholesterolemia, coronary artery disease, and right-to-left shunt (RLS) at rest were significantly associated with prior stroke. Using a pre-specified multivariable logistic regression model, age (Odds Ratio 1.06), BMI (OR 1.06), hypercholesterolemia (OR 1.90) and RLS at rest (OR 1.88) were strongly associated with prior stroke.Based on these factors, we developed a nomogram to illustrate the strength of the relation of individual factors to prior stroke. Conclusion: In patients with CS and PFO, the likelihood of prior stroke is associated with both, PFO-related and PFO-unrelated factors.


Oxidative stress and endothelial dysfunction in aortas of aged spontaneously hypertensive rats by NOX1/2 is reversed by NADPH oxidase inhibition.
Arterial hypertension is associated with increased levels of reactive oxygen species, which may scavenge endothelium-derived NO and thereby diminish its vasorelaxant effects. However, the quantitatively relevant source of reactive oxygen species is unclear. Thus, this potential pathomechanism is not yet pharmacologically targetable. Several enzymatic sources of reactive oxygen species have been suggested: uncoupled endothelial NO synthase, xanthine oxidase, and NADPH oxidases. Here we show that increased reactive oxygen species formation in aortas of 12- to 14-month-old spontaneously hypertensive rats versus age-matched Wistar Kyoto rats is inhibited by the specific NADPH oxidase inhibitor VAS2870 but neither by the xanthine oxidase inhibitor oxypurinol nor the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester. NADPH oxidase activity, as well as protein expression of its catalytic subunits, NOX1 and NOX2, was increased in the aortas of spontaneously hypertensive rats, whereas the expression of NOX4 protein, the most abundant NOX isoform, was not significantly changed. Impaired acetylcholine-induced relaxation of spontaneously hypertensive rat aortas was significantly improved by VAS2870. In conclusion, NOX1 and NOX2 but not NOX4 proteins are increased in aged spontaneously hypertensive rat aortas. Importantly, these NOX isoforms, in particular, ectopic expression of NOX1 in endothelial cells, appear to affect vascular function in an NADPH oxidase inhibitor-reversible manner. NADPH oxidases may, thus, be a novel target for the treatment of systemic hypertension.


Mutations in JMJD1C are involved in Rett syndrome and intellectual disability.
Autism spectrum disorders are associated with defects in social response and communication that often occur in the context of intellectual disability. Rett syndrome is one example in which epilepsy, motor impairment, and motor disturbance may co-occur. Mutations in histone demethylases are known to occur in several of these syndromes. Herein, we aimed to identify whether mutations in the candidate histone demethylase JMJD1C (jumonji domain containing 1C) are implicated in these disorders. We performed the mutational and functional analysis of JMJD1C in 215 cases of autism spectrum disorders, intellectual disability, and Rett syndrome without a known genetic defect. We found seven JMJD1C variants that were not present in any control sample (~ 6,000) and caused an amino acid change involving a different functional group. From these, two de novo JMJD1C germline mutations were identified in a case of Rett syndrome and in a patient with intellectual disability. The functional study of the JMJD1C mutant Rett syndrome patient demonstrated that the altered protein had abnormal subcellular localization, diminished activity to demethylate the DNA damage-response protein MDC1, and reduced binding to MECP2. We confirmed that JMJD1C protein is widely expressed in brain regions and that its depletion compromises dendritic activity. Our findings indicate that mutations in JMJD1C contribute to the development of Rett syndrome and intellectual disability.Genet Med 18 1, 378-385.


Dynamic Consolidation for Continual Learning.
Training deep learning models from a stream of nonstationary data is a critical problem to be solved to achieve general artificial intelligence. As a promising solution, the continual learning (CL) technique aims to build intelligent systems that have the plasticity to learn from new information without forgetting the previously obtained knowledge. Unfortunately, existing CL methods face two nontrivial limitations. First, when updating a model with new data, existing CL methods usually constrain the model parameters within the vicinity of the parameters optimized for old data, limiting the exploration ability of the model; second, the important strength of each parameter (used to consolidate the previously learned knowledge) is fixed and thus is suboptimal for the dynamic parameter updates. To address these limitations, we first relax the vicinity constraints with a global definition of the important strength, which allows us to explore the full parameter space. Specifically, we define the important strength as the sensitivity of the global loss function to the model parameters. Moreover, we propose adjusting the important strength adaptively to align it with the dynamic parameter updates. Through extensive experiments on popular data sets, we demonstrate that our proposed method outperforms the strong baselines by up to 24% in terms of average accuracy.


[The choice of antibacterial therapy for the children with labial and palatal cleft admitted to a surgical clinic].
For the purpose of the present study, faucial smears were obtained for the microbiological examination and the choice of adequate antibacterial therapy from the children presenting with pathological changes in the pharyngeal lymphoid tissue ring (congenital isolated labial and palatal cleft). The majority of the patients were children during the first year of life who had Gram-negative microorganisms in the oral cavity from day 1 after admission to the surgical clinic. The data obtained show that the development of intercurrent diseases and postoperative complications can be prevented by the parenteral application of cephalosporins of the III and IV generations as well as by oral administration of cefixime and protected aminopenicillins.


Does socioeconomic disparity in cancer incidence vary across racial/ethnic groups?
Very few studies have simultaneously examined incidence of the leading cancers in relation to socioeconomic status (SES) and race/ethnicity in populations including Hispanics and Asians. This study aims to describe SES disparity in cancer incidence within each of four major racial/ethnic groups (non-Hispanic white, black, Hispanic, and Asian/Pacific Islander) for five major cancer sites, including female breast cancer, colorectal cancer, cervical cancer, lung cancer, and prostate cancer. Invasive cancers of the five major sites diagnosed from 1998 to 2002 (n = 376,158) in California were included in the study. Composite area-based SES measures were used to quantify SES level and to calculate cancer incidence rates stratified by SES. Relative index of inequality (RII) was generated to measure SES gradient of cancer incidence within each racial/ethnic group. Significant variations were detected in SES disparities across the racial/ethnic groups for all five major cancer sites. Female breast cancer and prostate cancer incidence increased with increased SES in all groups, with the trend strongest among Hispanics. Incidence of cervical cancer increased with decreased SES, with the largest gradient among non-Hispanic white women. Lung cancer incidence increased with decreased SES with the exception of Hispanic men and women, for whom SES gradient was in the opposite direction. For colorectal cancer, higher incidence was associated with lower SES in non-Hispanic whites but with higher SES in Hispanics and Asian/Pacific Islander women. Examining SES disparity stratified by race/ethnicity enhances our understanding of the complex relationships between cancer incidence, SES, and race/ethnicity.


[Sertraline and acute pancreatitis: a case-report].
Acute pancreatitis is a severe disease with considerable morbidity and mortality. Many risk factors are causally related to acute pancreatitis. In this report, a case of acute pancreatitis with possible causal relationship with the use of a selective serotonin reuptake inhibitor, sertraline, will be discussed. After one month of treatment with sertraline, a female patient, 55 years-old, developed a severe abdominal pain and showed a serum amylase elevation. She was admitted to the hospital and the use of sertraline was interrupted. After that, the symptoms remitted and the serum amylase level returned to normal. Because of the potential severity of this disease and the widespread use of sertraline, this association should be reminded when investigating possible causes for acute pancreatitis.


Effect of the aqueous extract of Foeniculum vulgare (fennel) on the kidney in experimental PCOS female rats.
Foeniculum vulgare seed (F. vulgare) is an herbal plant which is used with phytoestrogene compounds for polycystic ovary syndrome (PCOS) treatment. In this research, renoprotective effect of the aqueous extract of Foeniculum vulgare (AEF) in experimental PCOS female rats is studied. Forty female rats were randomly divided into five groups. The first group served as control, was injected with an equivalent volume (0.2 ml) of normal saline, and received normal diet. Animals in the second group were non poly cystic ovary syndrome (PCOS) rats which were treated with intragastric administration of aqueous extract of F. vulgare (150 mg/kg b.w.). In the third group, the rats were treated with intraperitoneal injection of estradiolvalerate (EV) (4 mg in 0.2 ml of sesame oil). The fourth groups were treated with EV and AEF (150mg/kg bw) with the same route. The fifth groups were treated with EV and AEF (100mg/kg bw). After 4 weeks of study, all of the rats were sacrificed, their kidneys tissues were processed for light microscopy, and some biochemical parameters of serum were measured. The mean values of blood urea nitrogen in PCOS rats treated with low dose of AEF and EV and non-treated, was significantly (p<0.05) increased compared with non-PCOS and PCOS rats treated with high dose of AEF. Moreover, histopathological changes of kidney samples were comparable in PCOS rats with respect to treated groups with AEF. Aqueous extract of fennel seed showed the beneficial effect (especially at dose of 150 mg/kg b.w.) on renal function in PCOS rats.


Corneal angiogenic privilege and its failure.
The cornea actively maintains its own avascular status to preserve its ultimate optical function. This corneal avascular state is also defined as "corneal angiogenic privilege", which results from a critical and sensitive balance between anti-angiogenic and pro-angiogenic mechanisms. In our review, we aim to explore the complex equilibrium among multiple mediators which prevents neovascularization in the resting cornea, as well as to unveil the evolutive process which leads to corneal angiogenesis in response to different injuries.


Relationship of biomedical science content acquisition performance to students' level of PBL group interaction: are students learning during PBL group?
This study assessed biomedical science content acquisition from problem-based learning (PBL) and its relationship to students' level of group interaction. We hypothesized that learning in preparation for exams results primarily from individual study of post-case learning objectives and that outcomes would be unrelated to students' group involvement. During dental curricular years 1 and 2, student-generated biomedical learning issues (LIs) were identified from six randomly chosen PBL cases. Knowledge and application of case concepts were assessed with quizzes based on the identified LIs prior to dissemination of the learning objectives. Students and facilitators were surveyed on students' level of group involvement for the assessed LI topics. Year 1 students had significantly higher assessment scores (p=0.0001). For both student classes, means were significantly higher for the recall item (Q1) than for the application item (Q2). Q1 scores increased along with the student's reported role for Year 1 (p=0.04). However, there was no relationship between the student's reported role and Q1 for Year 2 (p=0.20). There was no relationship between the student's reported role and Q2 for Year 1 (p=0.09) or Year 2 (p=0.19). This suggests that students' level of group involvement on the biomedical learning issues did not significantly impact students' assessment performance.


Determination of alkali and halide monovalent ion parameters for use in explicitly solvated biomolecular simulations.
Alkali (Li(+), Na(+), K(+), Rb(+), and Cs(+)) and halide (F(-), Cl(-), Br(-), and I(-)) ions play an important role in many biological phenomena, roles that range from stabilization of biomolecular structure, to influence on biomolecular dynamics, to key physiological influence on homeostasis and signaling. To properly model ionic interaction and stability in atomistic simulations of biomolecular structure, dynamics, folding, catalysis, and function, an accurate model or representation of the monovalent ions is critically necessary. A good model needs to simultaneously reproduce many properties of ions, including their structure, dynamics, solvation, and moreover both the interactions of these ions with each other in the crystal and in solution and the interactions of ions with other molecules. At present, the best force fields for biomolecules employ a simple additive, nonpolarizable, and pairwise potential for atomic interaction. In this work, we describe our efforts to build better models of the monovalent ions within the pairwise Coulombic and 6-12 Lennard-Jones framework, where the models are tuned to balance crystal and solution properties in Ewald simulations with specific choices of well-known water models. Although it has been clearly demonstrated that truly accurate treatments of ions will require inclusion of nonadditivity and polarizability (particularly with the anions) and ultimately even a quantum mechanical treatment, our goal was to simply push the limits of the additive treatments to see if a balanced model could be created. The applied methodology is general and can be extended to other ions and to polarizable force-field models. Our starting point centered on observations from long simulations of biomolecules in salt solution with the AMBER force fields where salt crystals formed well below their solubility limit. The likely cause of the artifact in the AMBER parameters relates to the naive mixing of the Smith and Dang chloride parameters with AMBER-adapted Aqvist cation parameters. To provide a more appropriate balance, we reoptimized the parameters of the Lennard-Jones potential for the ions and specific choices of water models. To validate and optimize the parameters, we calculated hydration free energies of the solvated ions and also lattice energies (LE) and lattice constants (LC) of alkali halide salt crystals. This is the first effort that systematically scans across the Lennard-Jones space (well depth and radius) while balancing ion properties like LE and LC across all pair combinations of the alkali ions and halide ions. The optimization across the entire monovalent series avoids systematic deviations. The ion parameters developed, optimized, and characterized were targeted for use with some of the most commonly used rigid and nonpolarizable water models, specifically TIP3P, TIP4P EW, and SPC/E. In addition to well reproducing the solution and crystal properties, the new ion parameters well reproduce binding energies of the ions to water and the radii of the first hydration shells.


Effect of Structured Information on Immediate Preoperative Anxiety and Uncertainty for Women Undergoing Laparoscopic Hysterectomy.
Purpose of this study was to identify the effect of structured information on immediate preoperative anxiety and uncertainty for women undergoing total laparoscopic hysterectomy. Sixty women who were admitted for total laparoscopic hysterectomy were recruited at a university hospital in Gyeonggi-do from June to October 2014. Thirty women were assigned to either the experimental or the control group. Women in the experimental group were provided structured information, which consisted of visual and auditory materials about surgical preparation and process, practical experience on devices such as IV-PCA pump and Inspiro-meter and actual experience on route to go to the operating room. State-anxiety, uncertainty, and blood pressure and pulse rate as biological indicators were measured before and after the intervention to examine the effect. Significant group differences were found on state anxiety, uncertainty, including ambiguity, inconsistency, and unpredictability at the holding area. There was a significant difference on pulse rate in the operating room between the two groups. Findings demonstrated that the structured information provided for women undergoing laparoscopic hysterectomy preoperatively was effective on immediate preoperative anxiety and uncertainty. Nurses may contribute to decreasing patients' anxiety and uncertainty by utilizing this structured information preoperatively.


Influence of dispersion length on leaching calculated with PEARL, PELMO and PRZM for FOCUS groundwater scenarios.
Harmonisation of the assessment of pesticide leaching to groundwater for EU registration is desirable to minimise confusion in the decision-making process at EU level. Recently, the FOCUS groundwater scenarios have been developed for three chromatographic models (PEARL, PELMO and PRZM) to increase this harmonisation. This study investigates the role of dispersion parameterisation in explaining the cause of the differences in pesticide leaching calculated by these models. PEARL describes dispersion via a physical parameter, ie the dispersion length. PELMO and PRZM simulate dispersion via a numerical procedure which generates an effective dispersion length equal to 0.5 times the thickness of the numerical compartments. The hypothesis was tested that the difference in the dispersion length input parameter (ie 5 cm for PEARL and about 2.5 cm for PELMO and PRZM) is a major cause of the difference in calculated leaching. It was tested whether results of PEARL calculations with a dispersion length of 2.5 cm corresponded much better to results of PELMO or PRZM than results of PEARL calculations with a dispersion length of 5 cm. This was done by calculations for one substance and all nine FOCUS scenarios and by calculations for a range of substances and two FOCUS scenarios (Châteaudun and Sevilla). All calculations were for winter wheat and an application at 1 day before emergence. Both tests showed that reduction of the dispersion length from 5 to 2.5 cm in PEARL led to a much better correspondence between PEARL and either PELMO or PRZM. Hence the hypothesis was supported. It is likely that harmonisation of the dispersion length in the FOCUS groundwater scenarios would reduce the differences in calculated leaching between PEARL and PELMO or PRZM considerably for part of these scenarios.


[Mathematical model of development of long-term synaptic plasticity].
Proposed mathematical model is described the long-term synaptic plasticity creation as the postsynaptic process based on the number of membrane receptor increase. The transmitter as the "marker" of the receptor type synthesis and the protein kinase as the activator of this protein synthesis are proposed.


Antioxidant enzymes expression in lymphocytes of patients undergoing carotid endarterectomy.
To remedy carotid artery stenosis and prevent stroke surgical intervention is commonly used, and the gold standard being carotid endarterectomy (CEA). During CEA cerebrovascular hemoglobin oxygen saturation decreases and when this decrease reaches critical levels it leads to cerebral hypoxia that causes neuronal damage. One of the proposed mechanism that affects changes during CEA and contribute to acute brain ischemia (ABI) is oxidative stress. The increased production of reactive oxygen species and reactive nitrogen species during ABI may cause an unregulated inflammatory response and further lead to structural and functional injury of neurons. Antioxidant activity are involved in the protection against neuronal damage after cerebral ischemia. We hypothesized that neuronal injury and poor outcomes in patients undergoing CEA may be results of oxidative stress that disturbed function of antioxidant enzymes and contributed to the DNA damage in lymphocytes.


Unilateral and bilateral laparoscopic ovariectomy of mares by electrocautery.
Twelve horses underwent standing laparoscopic ovariectomy using electrocoagulation and fine dissection as the only means of achieving haemostasis of the severed ovarian pedicle. Four mares had bilateral ovariectomy performed as a treatment for aggressive behaviour thought to be associated with the oestrous cycle. Eight mares had unilateral ovariectomy performed for removal of a granulosa thecal cell tumour (GCT). Electrocoagulation provided an effective means of haemostasis in both normal and pathological ovaries. Only one case (removal of a GCT) had mild haemorrhage following electrocoagulation, necessitating the need for the application of endoscopic clips to achieve haemostasis. Six of the horses developed minor wound complications (none of them requiring any additional treatment). Long-term follow-up information showed complete resolution of abnormal behaviour in all eight horses with GCTs, but in one of the four horses with normal ovaries the aggressive behaviour had not been completely resolved.


Effect of pre-slaughter fasting time on carcass yield, blood parameters and meat quality in broilers.
The aim of this study was to evaluate the effect of pre-slaughter fasting time on carcass yield, meat quality, blood parameters and glucose metabolism in broilers. Four hundred and fifty Arbor Acres (AA) broilers at 42 days of age were divided into 5 groups with 6 replicates in each group and 15 chickens as one replicate. Following this period, broilers from each group were distributed among five groups according to pre-slaughter fasting period as 4, 8, 12, 16 or 20 h. With increasing fasting time, the carcass yield (p<0.01), the breast muscles yield (p<0.01) and the thigh yield (p<0.01) of the broilers were all linearly increased. With increasing fasting time, the L* values (p<0.01), cooking loss (p=0.020), moisture content (p<0.01) in the leg muscles linearly downregulated, while the drip loss (p=0.043), pH45min (p<0.01) and pH24h (p<0.01) were linearly upregulated. A trend for a lower (p=0.071) shear force in the leg muscles was also observed in broilers fasted for longer time. Similar results were also found in breast muscles. The different fasting treatments did not influence the breast muscles glycogen content (p>0.10), while the increase of fasting time resulted in a linear decrease of the blood glucose (p=0.021) and, more specifically, the glycogen content of the liver and leg muscles (p<0.001). With increasing fasting time, the AST (p<0.01), UA (p<0.01) and TG (p<0.01) in serum linearly downregulated, while the ALT was linearly upregulated. The results of this study show a significant influence of fasting time on carcass yield and meat quality in broilers. Moderate fasting (8-12 h) before slaughter can reduce the weight loss of broilers. Avoid prolonged fasting (≥16 h) increased body weight loss, decreased slaughtering performance and fluctuating blood indexes of broilers.


Hyperscaling relationship between the interfacial tension of liquids and their correlation length near the critical point.
Interfaces involving coexisting phases in condensed matter are essential in many phenomena: wetting, nucleation, morphology, phase separation kinetics, membranes, phase coexistence in nanomaterials, etc. The majority of analytical theories available use concepts derived from mean field artifacts which do not describe adequately these systems. Satisfactory numerical simulation of interfaces at the atomistic to mesoscopic scale is still a challenge. In the present work, the interfacial tension between mixtures of organic solvents and water is obtained from mesoscopic computer simulations. The temperature dependence of the interfacial tension is found to obey a scaling law with an average critical exponent μ = 1.23. Additionally, we calculate the evolution of the correlation length, defined as the thickness of the interface between the immiscible fluids, as a function of temperature and find that it obeys also a scaling law with an average critical exponent being ν = 0.67. Finally, we show that the comparison of μ and ν for these binary mixtures constitutes the first test of Widom's hyperscaling relationship between these exponents in 3d, expressed as μ = ν (d - 1). Based on these values and those for the 3d Ising model it is argued that both systems belong to the same universality class, which opens up the way for the calculation of new scaling exponents.


Decreased STAT3 in human idiopathic fetal growth restriction contributes to trophoblast dysfunction.
Abnormal trophoblast function is associated with fetal growth restriction (FGR). The JAK-STAT pathway is one of the principal signalling mechanisms by which cytokines and growth factors modulate cell proliferation, differentiation, cell migration and apoptosis. The expression of placental JAK-STAT genes in human idiopathic FGR is unknown. In this study, we propose the hypothesis that JAK-STAT pathway genes are differentially expressed in idiopathic FGR-affected pregnancies and contribute to abnormal feto-placental growth by modulating the expression of the amino acid transporter SNAT2, differentiation marker CGB/human chorionic gonadotrophin beta-subunit (β-hCG) and apoptosis markers caspases 3 and 8, and TP53. Expression profiling of FGR-affected placentae revealed that mRNA levels of STAT3, STAT2 and STAT5B decreased by 69, 52 and 50%, respectively, compared with gestational-age-matched controls. Further validation by real-time PCR and immunoblotting confirmed significantly lower STAT3 mRNA and STAT3 protein (total and phosphorylated) levels in FGR placentae. STAT3 protein was localised to the syncytiotrophoblast (ST) in both FGR and control placentae. ST differentiation was modelled by in vitro differentiation of primary villous trophoblast cells from first-trimester and term placentae, and by treating choriocarcinoma-derived BeWo cells with forskolin in cell culture. Differentiation in these models was associated with increased STAT3 mRNA and protein levels. In BeWo cells treated with siRNA targeting STAT3, the mRNA and protein levels of CGB/β-hCG, caspases 3 and 8, and TP53 were significantly increased, while that of SNAT2 was significantly decreased compared with the negative control siRNA. In conclusion, we report that decreased STAT3 expression in placentae may contribute to abnormal trophoblast function in idiopathic FGR-affected pregnancies.


Sociopolitical control as a mediator between ethnic identity and social support on 30-day drug use among black girls.
While Black girls have lower rates of drug use, they face worse health and wellbeing consequences associated with drug use. Understanding which strengths-based factors serve as buffers to limit adverse outcomes related to drug use among Black girls is essential for prevention. This study investigated the mediating role of sociopolitical control on drug use among Black girls (n = 340). Using path analysis, models were tested to include the variables of interest. Sociopolitical control (e.g. leadership competency and policy control) significantly mediated the relationship between ethnic identity and social support on drug use. Implications from this study may consider bolstering empowerment-based strategies in drug use prevention for Black girls.


Health workers perceptions and attitude about Ghana's preparedness towards preventing, containing, and managing Ebola Virus Disease.
Ebola virus is highly infectious and the disease can be very fatal. The World Health Organization has declared the 2014-2015 Ebola Virus Disease outbreak a Public Health Emergency of International Concern. In response to this, preparations were made in various health facilities and entry points across Ghana. This study explored health workers perceptions, and attitude about Ghana's preparedness towards preventing and containing Ebola Virus Disease. We conducted a qualitative study in five (5) of the ten (10) regions in Ghana. Five focus group discussions (N = 44) were conducted among nurses; one in each region. In addition, ten (10) health workers (2 in each region) who are members of regional Ebola Virus Disease task force were recruited and interviewed. In the Greater Accra, Volta and Western regions that have ports, six (6) port health officials: two in each of these regions were also interviewed. The interviews were recorded digitally and transcribed verbatim. Thematic content analysis was used to analyze the transcripts with the aid of NVivo 10 software. The results of this study showed that Ghanaian health workers perceived the screening at various ports as important and ongoing but felt that the screenings at in-land ports were being undermined by the use of unapproved routes. Training of health workers was also being carried out in all the regions, however, there was a general perception among 33 out of 44 nurses that majority of health workers have not received training on Ebola Virus Disease prevention and management. Logistical challenges were also reported as some health facilities did not have adequate Personal Protective Equipment. In facilities where equipment was available, they were stored in places which are not easily accessible to health workers at all times of the day. Human resource preparation was also perceived to be a challenge as health workers (38/44 of nurses) generally expressed fear and unwillingness to work in Ebola treatment centres in the event of an outbreak in Ghana. Our study concludes that preparatory work for Ebola Virus Disease prevention and containment in Ghana is perceived as inadequate by health workers. Ghana needs to strengthen preparation in the area of training of health workers, provision and accessibility of Personal Protective Equipment and incentives for health workers to better position her to contain and manage any Ebola Virus Disease outbreak.


Modeling Neurological Diseases With Human Brain Organoids.
The complexity and delicacy of human brain make it challenging to recapitulate its development, function and disorders. Brain organoids derived from human pluripotent stem cells (PSCs) provide a new tool to model both normal and pathological human brain, and greatly enhance our ability to study brain biology and diseases. Currently, human brain organoids are increasingly used in modeling neurological disorders and relative therapeutic discovery. This review article focuses on recent advances in human brain organoid system and its application in disease modeling. It also discusses the limitations and future perspective of human brain organoids in modeling neurological diseases.


Outcomes after total hip replacement based on patients' baseline status: what results can be expected?
We evaluated patient satisfaction with total hip replacement (THR) to establish cut points of sufficient improvement based on the patient acceptable symptom state (PASS) and receiver operating characteristic (ROC) curves, and compared them with measures derived from the minimum clinically important difference (MCID), taking into account patients' baseline status. Two cohorts of prospectively recruited patients on waiting lists for THR were studied. Sociodemographic data and comorbidities were recorded. Patients completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and other patient-reported outcomes questionnaires before THR and 6 months afterward. Cut points of sufficient improvement were established by the PASS, ROC, and MCID and were compared. Patients satisfied with THR had, by preintervention WOMAC tertiles, gains of 19.4, 34.1, and 49.3 in the WOMAC pain domain and 17.8, 30.8, and 41.4 in the WOMAC functional limitation domain. The PASS cut points determined were 20, 25, and 25 for postintervention WOMAC pain and 28, 35, and 42 for functional limitation. ROC cut points were 19, 25, and 25 for postintervention pain and 26.4, 39, and 40 for functional limitation. Agreement among cut points classifying patients as responders to THR was 1.0 for pain with both PASS and ROC, and 0.85 for functional limitation; 0.6 for pain between MCID and PASS or ROC, and 0.58 and 0.60 for functional limitation. Cut points of expected gain after THR can help clinicians, researchers, and managers to identify suitable candidates for THR, although such measures must be used with caution.


Strategies to Enhance the Efficacy of T-Cell Therapy for Central Nervous System Tumors.
Mortality rates in patients diagnosed with central nervous system (CNS) tumors, originating in the brain or spinal cord, continue to remain high despite the advances in multimodal treatment regimens, including surgery, radiation, and chemotherapy. Recent success of adoptive cell transfer immunotherapy treatments using chimeric antigen receptor (CAR) engineered T cells against in chemotherapy resistant CD19 expressing B-cell lymphomas, has provided the foundation for investigating efficacy of CAR T immunotherapies in the context of brain tumor. Although significant efforts have been made in developing and translating the novel CAR T therapies for CNS tumors, including glioblastoma (GBM), researchers are yet to achieve a similar level of success as with liquid malignancies. In this review, we discuss strategies and considerations essential for developing robust preclinical models for the translation of T cell-based therapies for CNS tumors. Some of the key considerations include route of delivery, increasing persistence of T cells in tumor environment, remodeling of myeloid environment, establishing the window of treatment opportunity, harnessing endogenous immune system, designing multiple antigen targeting T cells, and rational combination of immunotherapy with the current standard of care. Although this review focuses primarily on CAR T therapies for GBM, similar strategies, and considerations are applicable to all CNS tumors in general.


Autonomous Multi-Platform Observations During the Salinity Processes in the Upper-ocean Regional Study.
The Salinity Processes in the Upper-ocean Regional Study (SPURS) aims to understand the patterns and variability of sea surface salinity. In order to capture the wide range of spatial and temporal scales associated with processes controlling salinity in the upper ocean, research vessels delivered autonomous instruments to remote sites, one in the North Atlantic and one in the Eastern Pacific. Instruments sampled for one complete annual cycle at each of these two sites, which are subject to contrasting atmospheric forcing. The SPURS field programs coordinated sampling from many different platforms, using a mix of Lagrangian and Eulerian approaches. This article discusses the motivations, implementation, and first results of the SPURS-1 and SPURS-2 programs.


In vitro and in vivo characterization of chimeric duck Tembusu virus based on Japanese encephalitis live vaccine strain SA14-14-2.
Duck Tembusu virus (DTMUV), a newly identified flavivirus, has rapidly spread to China, Malaysia and Thailand. The potential threats to public health have been well-highlighted; however its virulence and pathogenesis remain largely unknown. Here, by using reverse genetics, a recombinant chimeric DTMUV based on Japanese encephalitis live vaccine strain SA14-14-2 was obtained by substituting the corresponding prM and E genes (named ChinDTMUV). In vitro characterization demonstrated that ChinDTMUV replicated efficiently in mammalian cells with small-plaque phenotype in comparison with its parental viruses. Mouse tests showed ChinDTMUV exhibited avirulent phenotype in terms of neuroinvasiveness, while it retained neurovirulence from its parental virus DTMUV. Furthermore, immunization with ChinDTMUV was evidenced to elicit robust IgG and neutralizing antibody responses in mice. Overall, we successfully developed a viable chimeric DTMUV, and these results provide a useful platform for further investigation of the pathogenesis of DTMUV and development of a live attenuated DTMUV vaccine candidate.


2-(oxadiazolyl)- and 2-(thiazolyl)imidazo[1,2-a]pyrimidines as agonists and inverse agonists at benzodiazepine receptors.
Oxadiazoles, like the benzoyl group in a series of imidazo[1,2-a]pyrimidines, have been found to be metabolically stable alternatives to ester groups in benzodiazepine-receptor ligands. This change has lead to a number of compounds which bind to the receptors and which exhibit potent agonist activity in a food-motivated conflict test thought to predict anxiolytic properties. Compounds 4, 5, and 13 were equipotent with chlordiazepoxide but showed little or no myorelaxant effects. Replacing the oxadiazole group by thiazole gave compounds such as 23 which binds to the benzodiazepine receptor but exhibits the intrinsic activity of a partial inverse agonist in vivo.


Economic evaluation of continuous subcutaneous insulin infusion for children with diabetes - a pilot study: CSII application for children - economic evaluation.
The objective of this study is to assess the cost of using continuous subcutaneous insulin infusion to treat children with type-1diabetes in Bulgaria, considering changes in body mass index (BMI) and the glycated hemoglobin. The study was performed from the perspective of the Bulgarian National Health Insurance Fund (NHIF) and patients. A total of 34 pediatric type-1-diabetes patients were observed for 7 months, divided into 2 groups - on pumps and on insulin analogue therapy. Patient demographic data, BMI and glycated hemoglobin level were obtained and recorded. The cost of insulin, pumps, and consumables were calculated and compared with changes in glycated hemoglobin level. The incremental cost-effectiveness ratio was below the threshold value of gross domestic product per capita. The results were sensitive to changes in glycated hemoglobin level. Improvements associated with glycemic control led to a reduced glycated hemoglobin level that could ensure good diabetes management, but its influence on BMI in growing children remains unclear. Continuous subcutaneous insulin infusion appears to be more cost-effective for the Bulgarian pediatric population and health care system.


Prevention of drowning.
Drowning is a leading cause of injury-related death in children. In 2006, approximately 1100 US children younger than 20 years died from drowning. A number of strategies are available to prevent these tragedies. As educators and advocates, pediatricians can play an important role in the prevention of drowning.


A Tangled Autoimmune Trio: Multiple Sclerosis, Systemic Lupus Erythematosus and Antineutrophil Cytoplasmic Antineutrophil Cytoplasmic Antibody Vasculitis.
The coexistence of multiple autoimmune diseases in the same individual is unusual and has received little attention in the literature. We present a young female patient with multiple sclerosis, systemic lupus erythematosus, and biopsy-proven renal proteinase 3 antineutrophil cytoplasmic antibodyassociated vasculitis who responded well to intravenous rituximab clinically and serologically.


Microleakage and confocal laser studies of 2 single-step self-etching bonding agents/systems.
This study investigated the microleakage, etching ability, and dentin-restorative interface of 2 different single-step self-etching bonding agents with compomers as restoratives. Fifteen extracted noncarious human premolars were used for each dental material system. The bonding agent Xeno III was used with their compomer Dyract AP (Dentsply) and Adper Prompt L-Pop with their compomer Z2000 (3M Espe). Cylindrical cavities were prepared in enamel and dentin on the buccal surface at the cementoenamel junction and restored. The specimens were thermocycled and cut into slices, and the depth of dye penetration scored. The dentine-restorative interface was examined through a confocal scanning laser microscope. Microleakages between the enamel and dentin sides differed significantly for Xeno (Wilcoxon rank sum test; P = .0058) as well as for Prompt (P = .0106), while the microleakages between the dentin sides of Xeno and Prompt did not differ significantly. However, between the enamel sides, a significant difference was found (P = .000), with the highest value for Prompt. The confocal laser studies showed tag formation, penetration of the bonding agents deep into the tubules, and hybrid layer formation for both bonding agents. It can be concluded that both adhesives gave microleakage values for dentin that are on the lower side. However, careful inspection of the enamel side indicated that both cannot be recommended for enamel sealing.


A Cu-Pd single-atom alloy catalyst for highly efficient NO reduction.
A series of Cu-Pd alloy nanoparticles supported on Al2O3 were prepared and tested as catalysts for deNO x reactions. XRD, HAADF-STEM, XAFS, and FT-IR analyses revealed that a single-atom alloy structure was formed when the Cu/Pd ratio was 5, where Pd atoms were well isolated by Cu atoms. Compared with Pd/Al2O3, Cu5Pd/Al2O3 exhibited outstanding catalytic activity and N2 selectivity in the reduction of NO by CO: for the first time, the complete conversion of NO to N2 was achieved even at 175 °C, with long-term stability for at least 30 h. High catalytic performance was also obtained in the presence of O2 and C3H6 (model exhaust gas), where a 90% decrease in Pd use was achieved with minimum evolution of N2O. Kinetic and DFT studies demonstrated that N-O bond breaking of the (NO)2 dimer was the rate-determining step and was kinetically promoted by the isolated Pd.


Zinc supplementation in infants with asymmetric intra uterine growth retardation; effect on growth, nutritional status and leptin secretion.
To analyse the effect of zinc supplementation in growth and nutritional status of a homogeneous group of newborns with intra uterine growth retardation and asymmetric growth. The effect of changes of zinc status on growth and leptin serum concentrations was also analysed. A double blind, randomised clinical trial was designed in order to detect differences in growth between zinc and placebo groups during the first 6 months of life. 31 infants were included either to the zinc group (n = 14) (38.8+/-1.4 weeks GA, 2,171+/-253 g body weight) or the placebo group (n = 17) (38.9+/-1.1 weeks GA, 2,249+/-220 g body weight). The zinc group received a supplement of 3 mg elemental zinc per day (as zinc sulphate). There were not significant differences between groups for anthropometric measurements through the study period. We found a significant effect of the study group, in hair zinc concentrations, but not in serum zinc concentrations; post-hoc comparisons for hair zinc revealed that there were significant differences between groups at 1, 2, and 6 months of age. Changes in serum and hair zinc concentrations from baseline to 6 months, showed significant correlations with changes in weight/age and length/age z-scores, in the supplement group. Changes in leptin serum concentrations during follow-up, showed significant correlations with changes in sum of 4 skinfolds and weight/age z-score, in the placebo group. Changes in hair zinc concentration through the study period showed significant correlations with changes in leptin serum concentrations from baseline to 6 months of follow-up. In a homogeneous group of intra uterine growth retardation infants with asymmetric growth, 3 mg/day zinc supplementation do not show significant improvements in weight and length growth. Changes in zinc status were related with changes in weight and length during the first 6 months of life. Changes in leptin serum concentrations were related with changes in the anthropometric indices of body fat accretion.


Kaleidoscope modes in large aperture Porro prism resonators.
We apply a new method of modeling Porro prism resonators, using the concept of rotating loss screens, to study stable and unstable Porro prism resonator. We show that the previously observed petal--like modal output is in fact only the lowest order mode, and reveal that a variety of kaleidoscope beam modes will be produced by these resonators when the intra--cavity apertures are sufficiently large to allow higher order modes to oscillate. We also show that only stable resonators will produce these modes.