The 5-HTTLPR polymorphism modulates the influence on environmental stressors on peripartum depression symptoms.
Maternal depression during the peripartum period has an incidence of about 13%. Individuals with specific genetic predispositions are more vulnerable to stressful life events suggesting that exploration of gene-environmental pathways might facilitate the identification of risk factors for peripartum depression. The aim of this study was to evaluate the influence of stressful life events in combination with the serotonin transporter gene 5-HTTLPR polymorphism on peripartum depressive symptoms. In a non-psychiatric cohort of 419 Caucasians, the severity of depression was assessed prospectively during pregnancy (3rd trimester) and the postpartum period (2-3 days and 6-8 months) using the Edinburgh Postnatal Depression Scale. Satisfaction with the partner and exposure to negative life events were evaluated using self-report questionnaires and the genotype of the 5-HTTLPR was assessed. Repeated measures generalized linear models were used to investigate the gene-environment interaction on depressive symptoms across late pregnancy and the postpartum period. The 5-HTTLPR S-allele carrier status predicted late postpartum depressive symptom severity only in the presence of negative life events. This interaction was not observed for depressive symptoms during the 3rd trimester or the early postpartum. In addition, S-allele carrier status increased the negative effects of dissatisfaction with the current partner on depressive symptoms in the late postpartum period. In this non-psychiatric cohort, the 5-HTTLPR interacts with both lifetime and current stressors to influence depressive symptoms in the late post partum period. These findings could have clinical implications by allowing identification of women at higher risk for developing postpartum depressive symptoms.


Inhibition of growth of Mycobacterium avium in murine and human mononuclear phagocytes by migration inhibitory factor.
Infections caused by Mycobacterium avium, the most common form of diseminated bacterial disease in AIDS patients, are difficult to treat because of their resistance to many antimycobacterial drugs. The results of the present study show that recombinant migration inhibitory factor, a 12-kDa molecule recently isolated by COS-1 cell expression screening of cDNA from a human T-cell hybridoma, has potent inhibitory activity on the growth of a panel of clinical isolates of M. avium within both bone-marrow-derived murine macrophages and cultured human blood monocytes. These cells cultured in recombinant migration inhibitory factor exhibit various signs of activation, including cell division, morphological changes such as evidence of substantial phagolysosomal fusion, and enhanced secretion of tumor necrosis factor.


Diagnosing cervical cancer and high-grade precursors by HPV16 transcription patterns.
Infections with high-risk human papillomaviruses (HPV), mainly HPV type 16, can cause malignant transformation of the human cervical epithelium and the development of cervical cancer (CxCa). A rapid and precise diagnosis of the precancerous lesions by conventional cytology or HPV DNA tests remains difficult and often leads to overtreatment. We quantitatively analyzed the HPV16 transcriptome of 80 HPV16 DNA-positive cervical scrapes classified as mild cytologic grade, including no intraepithelial lesion or malignancy (NIL/M; normal, n=25) and low-grade squamous intraepithelial lesion (LSIL; n=24), and severe cytologic grade, including high-grade squamous intraepithelial lesion (HSIL; n=24) and CxCa (n=7), with novel nucleic acid sequence-based amplification-Luminex assays. In severe lesions, HPV16 E6*II and E1C encoding transcripts were strongly upregulated, whereas spliced E1[SYMBOL: SEE TEXT]E4 and L1 encoding transcripts were markedly downregulated. Using a combination of the four marker transcripts, 100% of CxCa and 67% of HSIL cases were correctly identified as severe, and 74% of LSIL and 92% of NIL/M samples as mild cytologic grade. Compared with a commercially available HPV E6/E7 mRNA assay, the specificity of the marker combination for discriminating severe and mild cytologic lesions increased from 23% to 83%. In conclusion, we identified a novel HPV16 RNA pattern for grading of cervical lesions with a potentially high diagnostic value for the primary screening of CxCa precursors and the triage of cervical lesions.


Q fever: baseline monitoring of a sheep and a goat flock associated with human infections.
Animal losses due to abortion and weak offspring during a lambing period amounted up to 25% in a goat flock and up to 18% in a sheep flock kept at an experimental station on the Swabian Alb, Germany. Fifteen out of 23 employees and residents on the farm tested positive for Coxiella burnetii antibodies by enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay. Ninety-four per cent of the goats and 47% of the sheep were seropositive for C. burnetii by ELISA. Blood samples of 8% of goats and 3% of sheep were PCR positive. C. burnetii was shed by all tested animals through vaginal mucus, by 97% of the goats and 78% of the sheep through milk, and by all investigated sheep through faeces (PCR testing). In this outbreak human and animal infection were temporally related suggesting that one was caused by the other.


Induction of Porcine Dermatitis and Nephropathy Syndrome in Piglets by Infection with Porcine Circovirus Type 3.
Porcine circovirus type 3 (PCV3) is an emerging porcine circovirus that has been associated with porcine dermatitis and nephropathy syndrome (PDNS)-like clinical signs, reproductive failure, cardiac pathologies, and multisystemic inflammation in piglets and sows. Many aspects of PCV3 infection biology and pathogenesis, however, remain unknown. Here, we used a PCV3 virus stock from the rescue of an infectious PCV3 DNA clone to intranasally inoculate 4- and 8-week-old specific-pathogen-free piglets for evaluation of PCV3 pathogenesis. For 4-week-old piglets, typical clinical signs resembling those of PDNS-like disease were observed when piglets were inoculated with PCV3 alone or PCV3 combined with immunostimulation by keyhole limpet hemocyanin, with a mortality of 40% (2/5) for both types of inoculated piglets during a 28-day observation period postinoculation. Both types of inoculated piglets showed similar progressive increases in viral loads in the sera and had seroconverted to PCV3 capsid antibody after inoculation. Pathological lesions and PCV3-specific antigen were detected in various tissues and organs, including the lung, heart, kidney, lymph nodes, spleen, liver, and small intestine, in both types of inoculated piglets. The levels of proinflammatory cytokines and chemokines, including interleukin 1 beta (IL-1β), IL-6, IL-23α, gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and chemokine ligand 5 (CCL5), were significantly upregulated in both groups of inoculated piglets. Eight-week-old piglets also exhibited a similar PDNS-like disease but without death after PCV3 inoculation, as evidenced by pathological lesions and PCV3 antigen in various tissues and organs. These results show for the first time successful reproduction of PDNS-like disease by PCV3 infection and further provide significant information regarding the pathogenesis of PCV3 in piglets.IMPORTANCE Porcine circovirus type 3 (PCV3), an emerging porcine circovirus, is considered the cause of porcine dermatitis and nephropathy syndrome (PDNS)-like clinical signs and other systemic diseases in piglets and sows. To evaluate the pathogenesis of PCV3 infection in vivo, we used a PCV3 virus stock from the rescue of an infectious PCV3 DNA clone to intranasally inoculate 4- and 8-week-old specific-pathogen-free piglets and demonstrated successful reproduction of PDNS-like disease in animals that were inoculated with PCV3 alone or PCV3 combined with immunostimulation by keyhole limpet hemocyanin. Both 4- and 8-week-old PCV3-inoculated piglets showed similar increases in viral loads in the sera and had seroconverted to PCV3 capsid antibody. Pathological lesions and PCV3-specific antigen were detected in various tissues and organs, while numerous proinflammatory cytokines and chemokines in the sera were significantly upregulated after PCV3 inoculation. These results will provide significant information regarding the pathogenesis of PCV3 in piglets.


Non-dopaminergic mechanisms in the turning behavior evoked by intranigral opiates.
The turning effects of the unilateral intranigral injection of morphine and of different analogs of dynorphin and enkephalin were studied. All injections were made in awake rats through cronically implanted guide cannulae. Dynorphin1-13 at a dose of 10 micrograms (0.6 nmol) and dynorphin1-17 at a dose of 2 micrograms (0.9 nmol) produced contralateral circling when injected unilaterally in the substantia nigra (SN), lasting for about 1 h. D-Ala-dynorphin1-17, a more stable analog of dynorphin, produced at a dose of 2 micrograms (0.9 nmol), a longer-lasting effect. Injections of different enkephalin analogs were also made into the SN, [D-Ser2]-Leu-enkephalin (10 micrograms, 14.5 nmol) and [D-Ala2,D-Ala3]-Met-enkephalin (10 micrograms, 15 nmol) also produced contralateral circling after unilateral intranigral injection. This behavior lasted for 60-90 min, depending on the different enkephalins used. As already reported by Iwamoto and Way18 morphine also produced contralateral circling when injected into the SN. The circling evoked by all these opiates was completely antagonized by 5 mg/kg of naltrexone s.c. In order to study the role of the dopaminergic nigrostriatal system, we made unilateral lesions of the medial forebrain bundle (MFB) with 6-hydroxydopamine (6-OHDA) and kainic acid lesions of the striatum and we looked at the effect elicited by these lesions on the behavior produced by the above compounds when injected into the SN. The lesion of the dopaminergic nigrostriatal system failed to affect either the number of turns or the duration of the contralateral circling produced by unilateral injections of morphine, dynorphin and enkephalin analogs into the SN correspondent to the lesioned side. On the other hand kainate lesions of the body of the caudate potentiated the turning induced by intra-SN morphine and dynorphin. Therefore it appears that the dopaminergic nigrostriatal system is not essential in the expression of the contraversive turning behavior produced by intranigral injections of endogenous opiates or morphine and that opiates might produce dopamine-like effects indirectly, through the inhibition of nigral non-dopaminergic output neurons.


Evaluation of suitable reference genes in Brassica juncea and its wild relative Camelina sativa for qRT-PCR analysis under various stress conditions.
Quantitative real-time PCR (qRT-PCR) is an efficient method to estimate the gene expression levels but the accuracy of its result largely depends on the stability of the reference gene. Many studies have reported considerable variation in the expression of reference genes (RGs) in different tissue and conditions. Therefore, screening for appropriate RGs with stable expression is crucial for functional analysis of the target gene. Two closely related crucifers Brassica juncea (cultivated) and Camelina sativa (wild) respond differently towards various abiotic and biotic stress where C. sativa exhibits higher tolerance to various stress. Comparative gene expression analysis of the target genes between two such species is the key approach to understand the mechanism of a plant's response to stress. However, using an unsuitable RG can lead to misinterpretation of expression levels of the target gene in such studies. In this investigation, the stability of seven candidate RGs including traditional housekeeping genes (HKGs) and novel candidate RGs were identified across diverse sample sets of B. juncea and C. sativa representing- hormone treated, wounded, Alternaria brassicae inoculated and combination treated samples (exogenous hormone treatment followed by A. brassicae inoculation). In this investigation, we identified stable RGs in both the species and the most suitable RGs to perform an unbiased comparative gene expression analysis between B. juncea and C. sativa. Results revealed that TIPS41 and PP2A were identified as the overall best performing RGs in both the species. However, the most suitable RG for each sample subset representing different condition must be individually selected. In Hormone treated and wounded samples TIPS41 expressed stably in both the species and in A. brassicae inoculated and combination treatment performance of PP2A was the best. In this study, for the first time, we have identified and validated stable reference gene in C. sativa for accurate normalization of gene expression data.


Tracheal and tracheostomal hypergranulation and related stenosis in long-term cannulated patients: does the tracheostomy procedure make a difference?
Long-term cannulated patients are at risk of developing tracheal and tracheostomal hypergranulation. This study evaluated the incidence of hypergranulation and related tracheal stenosis in long-term cannulated patients. The relation between hypergranulation, specific tracheostomy techniques, and the duration of cannulation was investigated. A prospective observational study was conducted to analyze tracheostomal and tracheal hypergranulation in long-term cannulated patients. We compared complication rates in 344 postacute patients. Tracheas and tracheostomas were inspected visually and endoscopically at admission and at regular tube changes every 2 weeks until decannulation or discharge. Hypergranulation appeared 3 times as often in the tracheostoma (n=338) as in the trachea (n = 109). There was no influence of the tracheostomy procedure on the frequency (p = 0.931), location (tracheostoma, p = 0.947; trachea, p = 0.918), or severity (stenoses grade I, p = 0.910; grade II, p = 0.649; grade III, p = 0.304) of the hypergranulation. The main factors to account for hypergranulation were the duration of cannulation (p < 0.001) and age (p = 0.033). There was no influence of tracheostomy techniques on hypergranulation. Its development depends on the duration of cannulation. It is recommended to keep the duration of cannulation as short as possible with respect to the underlying neurologic impairment.


Effect of adaptive servo-ventilation on 1-year prognosis in heart failure patients.
Adaptive servo-ventilation (ASV) has been used as therapy for heart failure (HF). The objective of the present study was to estimate the effect of ASV on 1-year prognosis in HF patients. After optimizing medical therapy, a 1-year follow-up study was conducted of 85 HF patients (mean age, 72 ± 10 years; 46 men), categorized as New York Heart Association class II-IV. The patients were classified into 2 groups based on adherence to ASV therapy. Use of ASV for ≥ 4h/night was designated as good adherence, and use of ASV for <4h/night was designated as poor adherence. The incidence of fatal cardiovascular events including death from progression of HF, cardioembolic stroke, and fatal cardiac arrhythmias was tracked. Fifty-seven patients were classified into the good adherence group. After 1-year follow-up, the survival rate calculated using Kaplan-Meier analysis was significantly higher in the good adherence group than in the poor adherence group (P=0.0046, log-rank test). In a Cox proportional hazards model, the odds ratio (95% confidence interval) of fatal cardiovascular events was 0.53 (0.27-0.99) for the good ASV adherence group (P=0.046). ASV prevents fatal cardiovascular events and improves survival in HF patients.


[Emergency and hypertensive crisis: definition and treatment].
The opinions on how fast high blood pressure values should be lowered in emergencies have changed over the last years. It seems now more and more reasonable to lower high blood pressure values over several hours rather than several minutes. In some cases, however, a rapid reduction of elevated blood pressure may be necessary. In these cases the risks of a rapid decrease of blood pressure with respect to cerebrovascular circulation have to be considered.


Interleukin-1 receptor mRNA expression in activated bovine leukocytes in vitro.
Interleukin-1 (IL-1) is a key player in inflammation and the immune response. To better understand the complex interactions of IL-1 and its receptors in inflammation, we need to investigate how type I and type II IL-1 receptors (IL-1RI and IL-1RII) are regulated by cytokines and other mediators. Using semiquantitative reverse transcriptase PCR and Northern analysis, we examined the regulation of IL-1RI and IL-1RII mRNA levels in bovine polymorphonuclear leukocytes (PMNs) (i.e., neutrophils) and peripheral blood mononuclear cells (PBMCs) in vitro. IL-1RI mRNA levels were up-regulated in PBMCs by recombinant bovine IL-1beta (rBoIL-1beta), recombinant bovine granulocyte-macrophage colony-stimulating factor (rBoGM-CSF), rBoIL-4, recombinant bovine gamma interferon (rBoIFN-gamma), and dexamethasone. IL-1RI mRNA was increased in bovine PMNs exposed to rBoGM-CSF, rBoIL-4, and dexamethasone but was down-regulated by rBoIL-1beta and rBoIFN-gamma. IL-1RII mRNA was increased in bovine PBMCs and PMNs after exposure to rBoIL-1beta, rBoGM-CSF, rBoIL-4, and dexamethasone. In contrast, rBoIFN-gamma down-regulated the expression of bovine IL-1RII mRNA in PBMCs. These findings suggest that the expression of bovine IL-1RI and IL-1RII mRNAs is regulated differently by certain soluble stimuli (e.g., IFN-gamma) in PMNs and PBMCs.


The validity of the Tritrac-R3D Activity Monitor for the assessment of physical activity in children.
The purpose of this study was to evaluate the validity of the Tritrac-R3D Activity Monitor, a new instrument designed to improve assessments of physical activity. Comparisons were made with a heart rate monitor and with a Caltrac Activity Monitor. Thirty-five children (ages 9-11 years) were monitored on 3 different school days with all 3 instruments. The Tritrac was moderately correlated with the heart rate monitor (r = .58) and highly correlated with the Caltrac monitor (r = .88). By taking advantage of the minute-by-minute timing capability of the Tritrac and the heart rate monitors, it was discovered that the correlations between these instruments were highest during free play situations (lunch/recess, recess, after school) and were lower when activity was more limited (class time) or structured (physical education). The ability of the Tritrac to assess activity on a minute-by-minute basis may greatly enhance its overall utility.


BAL fluid cytology in the assessment of infectious lung disease.
The need for rapid laboratory results has marked the application of bronchoalveolar lavage (BAL) fluid cytology as a valuable tool in the assessment of infectious lung conditions. The techniques of BAL fluid processing presented here can be performed in a microbiological laboratory. The diagnostic value of BAL fluid cytology for the prediction of ventilator-associated pneumonia is discussed.


Why do inhibitors develop? Principles of and factors influencing the risk for inhibitor development in haemophilia.
The formation of inhibitory alloantibodies is, in the postinfectious era, the most severe and costly complication of replacement therapy in patients with haemophilia. The complexity of the immune response to the infused factor becomes more and more obvious as knowledge in the area increases. Antibodies develop as a result of a complex multi-factorial interaction between antigen-presenting cells, T- and B-lymphocytes. Genetic susceptibility of cell surface molecules, such as the major histocompatibility complex, the T-cell receptor and cytokine receptors, as well as various immunomodulatory molecules have a major impact on the outcome. In addition, environmental factors probably influence the risk of inhibitor development. The current concept of inhibitor development is reviewed. A better understanding of the pathophysiological mechanisms involved will facilitate improvement of therapy in the future, and hopefully provide an opportunity to prevent this complication of treatment.


Biotransformation of the diphenyl ether herbicide lactofen and purification of a lactofen esterase from Brevundimonas sp. LY-2.
The diphenyl ether herbicide lactofen is commonly used to control broadleaf weeds. Once released into the environment, this herbicide is subject to microbial reactions. This study describes the biotransformation of lactofen by Brevundimonas sp. LY-2 isolated from enrichment cultures inoculated with soil sample. This strain degraded about 80% of 50 mg L(-1) lactofen in 5 days of incubation in flasks. The metabolic behaviors of the herbicide in the media are described. The results show a transformation pathway of lactofen by the bacterium leading to the formation of 1-(carboxy)ethyl-5-(2-chloro-4-(trifluoromethyl)phenoxy)-2-nitrobenzoate and ethanol. An esterase, which could cleave the right ester bond of the alkanoic side chain of lactofen, was purified 113.3-fold to homogeneity with 6.83% recovery. The current results suggested that Brevundimonas sp. LY-2 degraded lactofen via the ester bond cleavage catalyzed by esterase.


Variant innate immune responses of mammary epithelial cells to challenge by Staphylococcus aureus, Escherichia coli and the regulating effect of taurine on these bioprocesses.
Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are important pathogens causing subclinical and clinical bovine mastitis, respectively. Taurine, an organic acid found in animal tissues, has been used for the treatment of various superficial infections and chronic inflammations. We challenged a bovine mammary epithelial cell (MEC) line (MAC-T) or a mouse mammary epithelial cell line (EpH4-Ev) with either E. coli or S. aureus and compared the responses of MECs to these 2 pathogens. We also examined the regulatory effects of taurine on these responses. Receptor analyses showed that both TLR2 and TLR4 are upregulated upon exposure to either E. coli or S. aureus. Taurine pre-treatment dampened upregulation to some extent. E. coli and S. aureus stimulated comparable levels of ROS, which could be inhibited by taurine pre-treatment. E. coli infection elicited a dramatic change in iNOS expression. Taurine significantly decreased iNOS expression in the S. aureus challenged group. Protein microarray demonstrated that 32/40 and 8/40 inflammatory molecules/mediators were increased after E. coli or S. aureus challenge, respectively. The fold changes of most molecules were higher in the E. coli infection group than that in the S. aureus infection group. Taurine negatively regulated the inflammatory profile in both bacterial infections. Pro-inflammatory cytokines (such as TNF-α) connected with TLR activation were down-regulated by taurine pre-treatment. The influence of TAK-242 and OxPAPC on cytokine/molecule expression profiles to E. coli challenge are different than to S. aureus. Some important factors (MyD88, TNF-α, IL-1β, iNOS and IL-6) mediated by TLR activation were suppressed either in protein microarray or special assay (PCR/kits) or both. TAK-242 restrained ROS production and NAGase activity similar to the effect of taurine in E. coli challenge groups. The detection of 3 indices (T-AOC, SOD and MDA) reflecting oxidative stress in vivo, showed that taurine improved the antioxidant ability of cells. We conclude that taurine can regulate the inflammatory response during infection with E. coli and prevent cell damage by affecting the signaling pathways mediated by TLRs and by improving the antioxidant ability of cells. In S. aureus infections, taurine's antioxidant ability may be the primary means of resistance to inflammation. This study provides a better understanding of the inflammatory mechanisms of E. coli and S. aureus mastitis, and it provides a putative strategy for the prevention of this disease.


Risk factors for developing tuberculosis: a 12-year follow-up of contacts of tuberculosis cases.
Many risk factors for the development of tuberculosis (TB) have been reported but have not been simultaneously assessed. To determine the risk of developing TB associated with each risk factor, after adjusting for all others. We performed a population-based, retrospective cohort study of the contacts of TB cases recorded in British Columbia, Canada. Known risk factors for the development of TB were assessed over a 12-year period; Cox regression was used to estimate the hazard ratios (HRs) of TB, adjusting for the other factors. Among 33 146 TB contacts, 228 developed TB during the study period (TB rate 668 per 100,000 population, 95%CI 604-783). The main risk factors for TB development were malnutrition (HR 37.5), no treatment of latent TB infection (HR 25) or <6 months of treatment (HR 5.38), age 0-10 years (HR 7.87), being a household contact (HR 8.47) and having a tuberculin skin test induration of >or=5 mm (HR >or=4.99). Bacille Calmette-Guérin vaccination significantly reduced the risk of TB development (HR 0.32, 95%CI 0.20-0.50). Among contacts of TB cases, we have identified the few factors that carry a very high risk for developing TB. These factors identify populations at highest risk and permit more effective TB control.


Gemella haemolysans as an emerging pathogen for bacteremia among the elderly.
We report a patient of an 82-year-old woman with occult Gemella haemolysans bacteremia without a clear entry site. Gemella haemolysans is part of the normal human flora but can cause severe systemic infections such as infective endocarditis on rare occasions. In this patient, physical examination showed no localized symptoms, and a transthoracic echocardiogram showed no vegetation on the heart valves. The entry site for this pathogen was unclear. As the number of the elderly with asymptomatic infections has been increasing, clinicians should be aware of that this microorganism can cause occult bacteremia and infective endocarditis.


Escape to Create an Interactive and Engaging Learning Experience.
The American Nurses Credentialing Center and the Association for Nursing Professional Development purport the significance of active learner engagement and its positive effects on learner outcomes. This article describes the development and implementation of an escape room in the perioperative setting to support active learner engagement and enhance learner outcomes. [J Contin Educ Nurs. 2020;51(11):493-495.].


Leucaena leucocephala and adjacent native limestone forest habitats contrast in soil properties on Tinian Island.
An ex situ germplasm collection of the endangered Cycas micronesica was established in a transition zone between biodiverse native forest and mature stands of the invasive species Leucaena leucocephala. Soil chemical properties were determined for the 2 tree cover types to inform management decisions. Total carbon, total nitrogen, calcium, and net ammonification were greater in native forest cover than in L. leucocephala patches. Net nitrification and net mineralization were greater under L. leucocephala cover. Trace metals also differed between the 2 forest cover types, with chromium, cobalt, and nickel accumulating to greater concentration under L. leucocephala cover and zinc accumulating to greater concentration under native forest cover. The results indicated that L. leucocephala cover generated substantial changes in soil chemical properties when compared with native forest tree cover, illuminating one means by which understory vegetation may be affected by changes in invasive tree cover.


Molecular clock rates at loci under stabilizing selection.
Under stabilizing selection in a finite population, lambda, the rate of allelic substitutions at a locus is approximately lambda approximately mu(1 + S)-1/2, where mu is the mutation rate. S, the stringency of selection upon new mutants, is defined by S = NVm/Vs, where N is the population size and Vm/Vs is a measure of the average fitness decrease experienced by new mutants. The approximation holds both for a "lonely" locus, which is the sole provider of genetic variation for the character under selection, and for an "embedded" locus, which is not. In both cases I use the Crow and Kimura model of a continuum of alleles with Gaussian selection and mutation. Monte Carlo simulations corroborate the substitution rate formula. Some molecular evolution data suggest the potential utility and limitations of the formula for estimating population size, mutation, and selection parameters. This work agrees with the rest of nearly neutral theory in emphasizing the important role of population size for substitution rates.


Administration of Dexmedetomidine Does Not Produce Long-Term Protective Effect on Testicular Damage Post Testicular Ischemia-Reperfusion Injury.
After surgical correction of testicular torsion, up to 68% of ipsilateral testes undergo atrophy due to ischemia-reperfusion injury (IRI). Recent studies have shown that dexmedetomidine (Dex) alleviates IRI in various vital organs. However, those studies evaluated its protective effect on short-term reperfusion. We aimed to investigate whether Dex has a long-term protective effect against testicular injury after IRI. A total of 24 New Zealand white rabbits were randomly divided into three groups (n = 8/group): the control group (saline-infused rabbits without IRI), the IRI group (saline-injected rabbits with IRI), and the Dex group (Dex-injected rabbits with IRI). The spermatic cord of rabbits in IRI and Dex groups was ligated for 4 h, and 1 h before reperfusion, Dex was administered intraperitoneally at a dose of 50 μg/kg body weight in group Dex, whereas saline was administered at the same dose to the IRI and control groups. Rabbits were kept alive for 4 weeks post reperfusion, then the testes were harvested, and the rabbits were euthanized. Four weeks post reperfusion, testicular volumes of the affected side decreased considerably in the IRI and Dex groups compared to the control group, with no significant difference between the IRI and Dex groups. Compared to the control group, the Johnson score and the mean seminiferous tubular diameters were significantly decreased in the IRI and Dex groups, but no significant differences were observed after administration of Dex. There were no significant differences in malondialdehyde and superoxide dismutase levels between the groups treated with and without Dex. Dex administration 3 h after ischemia and 1 h before reperfusion did not demonstrate a significant protective effect against testicular injury 4 weeks after IRI in rabbits. Further research is needed to confirm the potential therapeutic effects of Dex by varying the experimental conditions.


Threshold collision-induced dissociation of Sr(2+)(H(2)O)(x) complexes (x=1-6): An experimental and theoretical investigation of the complete inner shell hydration energies of Sr(2+).
The sequential bond energies of Sr(2+)(H(2)O)(x) complexes, where x=1-6, are determined by threshold collision-induced dissociation using a guided ion beam tandem mass spectrometer equipped with an electrospray ionization source. The electrospray source produces an initial distribution of Sr(2+)(H(2)O)(x) complexes, where x=6-9. Smaller Sr(2+)(H(2)O)(x) complexes, where x=1-5, are accessed using a recently developed in-source fragmentation technique that takes place in the high pressure region of a rf-only hexapole ion guide. This work constitutes the first experimental study for the complete inner shell of any multiply charged ion. The kinetic energy dependent cross sections are determined over a wide energy range to monitor all possible dissociation products and are modeled to obtain 0 and 298 K binding energies for loss of a single water molecule. These binding energies decrease monotonically for the Sr(2+)(H(2)O) complex to Sr(2+)(H(2)O)(6). Our experimental results agree well with previous literature results obtained by equilibrium and kinetic studies for x=5 and 6. Because there has been limited theory for the hydration of Sr(2+), we also present an in-depth theoretical study on the energetics of the Sr(2+)(H(2)O)(x) systems by employing several levels of theory with multiple effective core potentials for Sr and different basis sets for the water molecules.


New clinical information and physician prescribing: How do pediatric labeling changes affect prescribing to children?
Our study examines how physician prescribing responds to new scientific information added to drug labels. We focus on a series of label changes with new information about the effects of drugs in children. The information arose in response to a 1997 policy, pediatric exclusivity, which gave drug sponsors a 6-month exclusivity extension for conducting additional pediatric studies of already marketed drugs. The information from these studies was expected to improve pediatric prescribing by promoting appropriate use and by reducing inappropriate off-label prescribing. However, there has been little study about the actual effects of these labeling changes on physician prescribing behavior. We use a difference-in-differences strategy to examine how pediatric prescriptions respond to different types of labeling changes. Our results show that most label changes lead to reductions in prescribing to children. We find that the largest drop in prescribing occurs when the label indicates a drug is not effective for children. The evidence suggests that the labeling changes alleviated physician uncertainty about prescribing drugs to children and reduced some inappropriate off-label use.


Matrine inhibits the proliferation of pituitary tumor cells by decreasing Foxo3a phosphorylation and promoting Foxo3a nuclear localization.
Pituitary tumors account for 10% of intracranial cancer, and are difficult to treat with chemotherapy. The aim of the present study was to explore the role of matrine on the proliferation of pituitary cancer cells, as well as the molecular mechanism of matrine in progression and development of pituitary tumors. Matrine significantly suppressed the proliferation of pituitary cancer cells in a dose- and time-dependent manner. Western blotting results showed that the phosphorylation levels of AKT serine/threonine kinase (Akt) and forkhead box O3A (Foxo3a) decreased as the concentration of matrine increased. Matrine increased the nuclear localization of Foxo3a and the expression of proapoptotic genes, such as BCL2 like 11 and BCL2 associated X apoptosis regulator, and inhibited the levels of cytoplasmic Foxo3a. In conclusion, matrine promoted cell death of pituitary cancer cells and was involved in Akt/Foxo3a signaling pathway.


Determinants of treatment-related paradoxical reactions during anti-tuberculosis therapy: a case control study.
Inflammatory response following initial improvement with anti-tuberculosis (TB) treatment has been termed a paradoxical reaction (PR). HIV co-infection is a recognised risk, yet little is known about other predictors of PR, although some biochemical markers have appeared predictive. We report our findings in an ethnically diverse population of HIV-infected and uninfected adults. Prospective and retrospective clinical and laboratory data were collected on TB patients seen between January 1999-December 2008 at four UK centres selected to represent a wide ethnic and socio-economic mix of TB patients. Data on ethnicity and HIV status were obtained for all individuals. The associations between other potential risk factors and PR were assessed in a nested case-control study. All PR cases were matched two-to-one to controls by calendar time and centre. Of 1817 TB patients, 82 (4.5 %, 95 % CI 3.6-5.5 %) were identified as having a PR event. The frequency of PR was 14.4 % (18/125; 95 % CI 8.2-20.6 %) and 3.8 % (64/1692; 2.9-4.7) for HIV-positive and HIV-negative individuals respectively. There were no differences observed in PR frequency according to ethnicity, although the site was more likely to be pulmonary in those of black and white ethnicity, and lymph node disease in those of Asian ethnicity. In multivariate analysis of the case-control cohort, HIV-positive patients had five times the odds of developing PR (aOR = 5.05; 95 % CI 1.28-19.85, p = 0.028), whilst other immunosuppression e.g. diabetes, significantly reduced the odds of PR (aOR = 0.01; 0.00-0.27, p = 0.002). Patients with positive TB culture had higher odds of developing PR (aOR = 6.87; 1.31-36.04, p = 0.045) compared to those with a negative culture or those in whom no material was sent for culture. Peripheral lymph node disease increased the odds of a PR over 60-fold 4(9.60-431.25, p < 0.001). HIV was strongly associated with PR. The increased potential for PR in people with culture positive TB suggests that host mycobacterial burden might be relevant. The increased risk with TB lymphadenitis may in part arise from the visibility of clinical signs at this site. Non-HIV immunosuppression may have a protective effect. This study highlights the difficulties in predicting PR using routinely available demographic details, clinical symptoms or biochemical markers.


Development of a Superconducting Differential Double Contour Interferometer.
We study operation of a new device, the superconducting differential double contour interferometer (DDCI), in the application for the ultrasensitive detection of magnetic flux and for digital read out of the state of the superconducting flux qubit. DDCI consists of two superconducting contours weakly coupled by Josephson junctions. In such a device a change of the critical current, caused by an external magnetic flux or a nearby electric current, happens in a step-like manner when the angular momentum quantum number changes by one in one of the two contours. With a choice of parameters, the DDCI may outperform traditional superconducting quantum interference devices.


Placing Abstract Concepts in Space: Quantity, Time and Emotional Valence.
Research has shown that abstract concepts are often conceptualized along horizontal and vertical axes. However, there are mixed results concerning which axis is preferred for which type of conceptual domain. For instance, it has been suggested that the vertical axis may be preferred for quantity in tasks using linguistic stimuli (e.g., 'more,' 'less'), whereas numerals (e.g., '1,' '2,' '3') may be more prone to horizontal conceptualization. In this study, we used a task with free response options to see where participants would place quantity words ('most,' 'more,' 'less,' 'least'), numerals ('2,' '4,' '7,' '9'), time words ('past,' 'future,' 'earliest,' 'earlier,' 'later,' 'latest') and emotional valence words ('best,' 'better,' 'worse,' 'worst'). We find that for quantity words, the vertical axis was preferred; whereas for numerals, participants preferred the horizontal axis. For time concepts, participants preferred the horizontal axis; and for emotional valence, they preferred the vertical axis. Across all tasks, participants tended to use specific axes (horizontal, vertical), rather than combining these two axes in diagonal responses. These results shed light on the spatial nature of abstract thought.


Quantitative Analysis Of User Interfaces For Large Electronic Home Appliances And Mobile Devices Based On Lifestyle Categorization Of Older Users.
Background/Study Context: The increasing longevity and health of older users as well as aging populations has created the need to develop senior-oriented product interfaces. This study aims to find user interface (UI) priorities according to older user groups based on their lifestyle and develop quality of UI (QUI) models for large electronic home appliances and mobile products. A segmentation table designed to show how older users can be categorized was created through a review of the literature to survey 252 subjects with a questionnaire. Factor analysis was performed to extract six preliminary lifestyle factors, which were then used for subsequent cluster analysis. The analysis resulted in four groups. Cross-analysis was carried out to investigate which characteristics were included in the groups. Analysis of variance was then applied to investigate the differences in the UI priorities among the user groups for various electronic devices. Finally, QUI models were developed and applied to those electronic devices. Differences in UI priorities were found according to the four lifestyles ("money-oriented," "innovation-oriented," "stability- and simplicity-oriented," and "innovation- and intellectual-oriented"). Twelve QUI models were developed for four different lifestyle groups associated with different products. Three washers and three smartphones were used as an example for testing the QUI models. The UI differences of the older user groups by the segmentation in this study using several key (i.e., demographic, socioeconomic, and physical-cognitive) variables are distinct from earlier studies made by a single variable. The differences in responses clearly indicate the benefits of integrating various factors of older users, rather than single variable, in order to design and develop more innovative and better consumer products in the future. The results of this study showed that older users with a potentially high buying power in the future are likely to have higher satisfaction when selecting products customized for their lifestyle. Designers could also use the results of UI evaluation for older users based on their lifestyle before developing products through QUI modeling. This approach would save time and costs.


Sense and sensitivity when correcting for observed exposures in randomized clinical trials.
Standard intent-to-treat analyses of randomized clinical trials can yield biased estimates of treatment efficacy and toxicity when not all patients comply with their assigned treatment. Flexible methods have been proposed which correct for this by modelling expected contrasts between an individual's observed outcome and his/her potential outcome in the absence of exposure. Because such comparisons often require untestable assumptions, a sensitivity analysis is warranted. We show how this can be performed in a meaningful and practically useful way. Following the approach of Molenberghs, Kenward and Goetghebeur in a missing data context, we evaluate the separate contributions of structural uninformativeness and sampling variation to uncertainty about the population parameters. This leads us to consider Honestly Estimated Ignorance Regions (HEIRs) and Estimated Uncertainty RegiOns (EUROs), respectively. We use the results to estimate the causal effect of observed exposure on successful blood pressure reduction in a randomized controlled clinical trial with partial non-compliance.


GABAergic modulation of performance in response inhibition and interference control tasks.
Inhibitory control is a crucial executive function with high relevance to mental and physical well-being. However, there are still unanswered questions regarding its neural mechanisms, including the role of the major inhibitory neurotransmitter, γ-aminobutyric acid (GABA). This study examined the effects of lorazepam (0.5 mg and 1 mg), a positive allosteric modulator at the GABAA receptor, on response inhibition and interference control. We also explored the heterogeneity of inhibitory control and calculated delta plots to explore whether lorazepam affects the gradual build-up of inhibition and activation over time. N = 50 healthy participants performed antisaccade, Eriksen flanker and Simon tasks in a within-subjects, placebo-controlled, double-blind randomized design. Lorazepam increased reaction time (RT) and error rates dose dependently in all tasks (p ⩽ 0.005). In the antisaccade and Simon tasks, lorazepam increased congruency effects for error rate (p ⩽ 0.029) but not RT (p ⩾ 0.587). In the Eriksen flanker task, both congruency effects were increased by the drug (p ⩽ 0.031). Delta plots did not reflect drug-induced changes in inhibition and activation over time. Delta plots for RT in the Simon task were negative-going, as expected, whereas those for the antisaccade and flanker tasks were positive-going. This study provides evidence for GABAergic involvement in performance on response inhibition and interference control tasks. Furthermore, our findings highlight the diversity of the broader construct of inhibitory control while also pointing out similarities between different inhibitory control tasks. In contrast to RT and error rates, the cognitive processes indexed by delta plots may not be sensitive to GABAergic modulation.


Characterization of mechanical behavior of an epithelial monolayer in response to epidermal growth factor stimulation.
Cell signaling often causes changes in cellular mechanical properties. Knowledge of such changes can ultimately lead to insight into the complex network of cell signaling. In the current study, we employed a combination of atomic force microscopy (AFM) and quartz crystal microbalance with dissipation monitoring (QCM-D) to characterize the mechanical behavior of A431 cells in response to epidermal growth factor receptor (EGFR) signaling. From AFM, which probes the upper portion of an individual cell in a monolayer of cells, we observed increases in energy dissipation, Young's modulus, and hysteresivity. Increases in hysteresivity imply a shift toward a more fluid-like mechanical ordering state in the bodies of the cells. From QCM-D, which probes the basal area of the monolayer of cells collectively, we observed decreases in energy dissipation factor. This result suggests a shift toward a more solid-like state in the basal areas of the cells. The comparative analysis of these results indicates a regionally specific mechanical behavior of the cell in response to EGFR signaling and suggests a correlation between the time-dependent mechanical responses and the dynamic process of EGFR signaling. This study also demonstrates that a combination of AFM and QCM-D is able to provide a more complete and refined mechanical profile of the cells during cell signaling.


'I can actually exercise if I want to; it isn't as hard as I thought': a qualitative study of the experiences and views of obese adolescents participating in an exercise therapy intervention.
A qualitative study nested within a randomized controlled trial explored obese adolescents' experiences of participation in an exercise therapy intervention. Semi-structured interviews were conducted with participants assigned to exercise therapy. Participants' reported feeling more energetic during and after exercise, than before. Many participants reported feeling happy/happier and expressed feeling better about themselves as individuals after the intervention. Most participants felt more confident in their ability to exercise regularly. Greater emphasis needs to be placed upon educating obese adolescents about the wide range of health benefits that exercise can provide, and that weight loss, while important, is only one such benefit.


Some factors in the choice of male or female sterilisation in Aberdeen.
In a random sample of 84 men and 167 women, medical considerations, an intransigent attitude of one partner or a fear of adverse effects, were related to the decision on which partner should seek sterilisation. Only 19% of couples felt that they had a real choice between male and female sterilisation.


Update on intrapartum fetal pulse oximetry.
This article examines the current status of fetal pulse oximetry (FPO) as a means of intrapartum assessment of fetal wellbeing. FPO has been developed to a stage where it is a safe and accurate indicator of intrapartum fetal oxygenation. In general, sliding the FPO sensor along the examiner's fingers and through the cervix, to lie alongside the fetal cheek or temple is easy The recent publication of a randomised controlled trial (RCT) of FPO versus conventional intrapartum monitoring has validated its use to reduce caesarean section rates for nonreassuring fetal status. An Australian multicentre RCT is currently underway. Maternal satisfaction rates with FPO are high. FPO may be used during labour when the electronic fetal heart rate trace is nonreassuring or when conventional monitoring is unreliable, such as with fetal arrhythmias. If the fetal oxygen saturation (FSpO2) values are < 30%, prompt obstetric intervention is indicated, such as fetal scalp blood sampling or delivery FSpO2 monitoring should not form the sole basis of intrapartum fetal welfare assessment. Rather, the whole clinical picture should be considered.


Post-dural puncture headache: Part II--prevention, management, and prognosis.
Post-dural puncture headache (PDPH) is a frequent complication of lumbar puncture, performed for diagnostic or therapeutic purposes or accidentally, as a complication of epidural anesthesia. As PDPH can be disabling, clinicians who perform these procedures should be familiar with strategies for preventing this disorder. Since the best preventative measures sometimes fail, clinicians should also be familiar with the therapeutic approaches for PDPH. Herein, we review the procedure-related risk factors for PDPH, the prognosis of PDPH and the studies of PDPH treatment. We divide the therapeutic approach to PDPH into 4 stages: conservative management, aggressive medical management, conventional invasive treatments, and the very rarely employed less conventional invasive treatments and provide management algorithm to facilitate treatment.


A role for ALF4 during gall and giant cell development in the biotic interaction between Arabidopsis and Meloidogyne spp.
Root-knot nematodes (RKNs; Meloidogyne spp.) are a major pest for the agriculture worldwide. RKNs induce specialized feeding cells (giant cells, GCs) inside galls which are de novo formed pseudo-organs in the roots that share similarities with other developmental processes as lateral root (LR) and callus formation or grafting involving new vascular development or pericycle proliferation. Hence, it is pertinent to study the molecular mechanisms directing the plant-nematode interaction. In this respect, ALF4 is a key gene during LR formation, vascular vessels reconnection in grafting, hormone-induced callus formation or de novo root organogenesis from leaf explants. Our results show that ALF4 is also induced in galls at early infection stages in an auxin-independent way. Furthermore, ALF4 activity is necessary for the formation of proper galls and GCs, as the mutant alf4-1 presents aberrant galls and GCs with severe structural abnormalities leading to a dramatic reduction in the nematode egg production. However, a low-reproduction rate is maintained, that might be explained by the local auxin maximum build by the nematodes in galls, partially rescuing alf4-1 phenotype. This would be similar to the partial rescue described for LR formation with exogenous auxins and also agrees with the LR emergence from alf4-1 galls but not from uninfected roots. In addition, ALF4 is also induced in syncytia formed by cyst nematodes. All these data support a pivotal role for ALF4 during de novo organogenesis processes induced by endoparasitic nematodes, in addition to its role in LR formation, callus development or vessel reconnection during grafting.


The Deficiency of Indoleamine 2,3-Dioxygenase Aggravates the CCl4-Induced Liver Fibrosis in Mice.
In the present study, we examined the role of indoleamine 2,3-dioxygenase (IDO) in the development of CCl4-induced hepatic fibrosis. The liver fibrosis induced by repetitive administration with CCl4 was aggravated in IDO-KO mice compared to WT mice. In IDO-KO mice treated with CCl4, the number of several inflammatory cells and the expression of pro-inflammatory cytokines increased in the liver. In the results, activated hepatic stellate cells (HSCs) and fibrogenic factors on HSCs increased after repetitive CCl4 administration in IDO-KO mice compared to WT mice. Moreover, the treatment with l-tryptophan aggravated the CCl4-induced hepatic fibrosis in WT mice. Our findings demonstrated that the IDO deficiency enhanced the inflammation in the liver and aggravated liver fibrosis in repetitive CCl4-treated mice.


Lead poisoning--a hazard of traffic and industries in Pakistan.
We measured blood lead level, hemoglobin, and urinary amino-levulinic acid (ALA) in industrial workers and in individuals exposed to vehicle smoke. Industrial workers and people exposed to traffic smoke had comparatively higher blood lead levels than the controls (p < 0.0001). Similarly, urinary ALA was 3.82 mg/dL in industrial subjects, 3.68 mg/dL in traffic-exposed people, and 0.8 mg/dL in control subjects (p < 0.001). The hemoglobin level was lower in the industrial group and in the traffic exposure group compared with the control group (p < 0.01). Traffic smoke-exposed persons, such as traffic police staff, had higher blood lead level than those handling lead material, Government Transport Service (GTS) workshop staff. The length of exposure showed no relationship with the lead levels. However, a positive correlation was observed between the duration of exposure and urinary ALA in both sample groups. The major signs and symptoms of the population studied included headache, generalized body pain, hypertension, and depression.


An efficient stereoselective synthesis of penaresidin a from (e)-2-protected amino-3,4-unsaturated sulfoxide.
An efficient, modular, asymmetric synthesis of penaresidin A is disclosed. A beta-protected amino-gamma,delta-unsaturated sulfoxide was prepared by stereoselective addition of the lithio anion of (R)-methyl p-tolyl sulfoxide to an unsaturated sulfinylimine. The pendant sulfoxide group was used as an intramolecular nucleophile to functionalize an alkene regio- and stereoselectively to furnish a bromohydrin, which was employed as the key intermediate in the preparation of the azetidine subunit of penaresidin A. The stereogenic centers of the side chain were introduced by a regioselective opening of an epoxide. Julia-Kocienski olefination was used to couple the azetidine and side chain subunits. The methodology disclosed herein is also useful for the synthesis of ribo- and arabino-phytosphingosines and compounds possessing the amino alcohol moiety.


Genome-Wide Analysis of the Homeobox Gene Family and Identification of Drought-Responsive Members in Populus trichocarpa.
Homeobox (HB) genes play critical roles in the regulation of plant morphogenesis, growth and development. Here, we identified a total of 156 PtrHB genes from the Populus trichocarpa genome. According to the topologies and taxonomy of the phylogenetic tree constructed by Arabidopsis thaliana HB members, all PtrHB proteins were divided into six subgroups, namely HD-ZIP, ZF-HD, HB-PHD, TALE, WOX and HB-OTHERS. Multiple alignments of conserved homeodomains (HDs) revealed the conserved loci of each subgroup, while gene structure analysis showed similar exon-intron gene structures, and motif analysis indicated the similarity of motif number and pattern in the same subgroup. Promoter analysis indicated that the promoters of PtrHB genes contain a series of cis-acting regulatory elements involved in responding to various abiotic stresses, indicating that PtrHBs had potential functions in these processes. Collinearity analysis revealed that there are 96 pairs of 127 PtrHB genes mainly distributing on Chromosomes 1, 2, and 5. We analyzed the spatio-temporal expression patterns of PtrHB genes, and the virus-induced gene silencing (VIGS) of PtrHB3 gene resulted in the compromised tolerance of poplar seedlings to mannitol treatment. The bioinformatics on PtrHB family and preliminary exploration of drought-responsive genes can provide support for further study of the family in woody plants, especially in drought-related biological processes. It also provides a direction for developing new varieties of poplar with drought resistance. Overall, our results provided significant information for further functional analysis of PtrHB genes in poplar and demonstrated that PtrHB3 is a dominant gene regulating tolerance to water stress treatment in poplar seedlings.


Preimplantation genetic screening: an effective testing for infertile and repeated miscarriage patients?
Aneuploidy in pregnancy is known to increase with advanced maternal age (AMA) and associate with repeated implantation failure (RIF), and repeated miscarriage (RM). Preimplantation genetic screening (PGS) has been introduced into clinical practice, screening, and eliminating aneuploidy embryos, which can improve the chance of conceptions for infertility cases with poor prognosis. These patients are a good target group to assess the possible benefit of aneuploidy screening. Although practiced widely throughout the world, there still exist some doubts about the efficacy of this technique. Recent randomized trials were not as desirable as we expected, suggesting that PGS needs to be reconsidered. The aim of this review is to discuss the efficacy of PGS.


Structural modifications and kinetic studies of the substrates involved in the final step of methane formation in Methanobacterium thermoautotrophicum.
The 2-(methylthio)ethanesulfonic acid (CH3-S-CoM) reductase catalyzes the final methane-yielding reaction in fastidiously anaerobic methanogenic archaebacteria. This step involves the reductive demethylation of CH3-S-CoM with reducing equivalents from N-7-(mercaptoheptanoyl)-L-threonine O3-phosphate (HS-HTP) to yield methane and the nonsymmetrical disulfide of 2-mercaptoethanesulfonic acid and HS-HTP. We chemically synthesized modified analogs of CH3-S-CoM (which has two carbons in the ethylene bridge) and of HS-HTP (which has seven carbons in the side chain); analog pairs possessed an overall correct number of side chain carbons (i.e., a total of nine in combination). They were simultaneously added to anaerobic cell extracts of Methanobacterium thermoautotrophicum delta H. The ability of the extracts to reductively demethylate the modified substrates was tested by gas chromatography. We also describe here previously unknown inhibitors of methanogenesis, 6-(methylthio)hexanoyl-L-threonine O3-phosphate (a structural analog of HS-HTP) and sodium bromomethanesulfonic acid (a structural analog of CH3-S-CoM). Both analogs were found to be effective competitive inhibitors with respect to HS-HTP. These substrate analogs were also found to inhibit a recently described photoactivation of homogeneous inactive reductase (K. D. Olson, C. W. McMahon, and R. S. Wolfe, Proc. Natl. Acad. Sci. USA 88:4099-4103, 1991). In addition, we probed the mechanism of action of a potent inhibitor of the enzyme, 2-bromoethanesulfonic acid, a structural analog of CH3-S-CoM.


Recycling probability and dynamical properties of germinal center reactions.
We introduce a new model for the dynamics of centroblasts and centrocytes in a germinal center. The model reduces the germinal center reaction to the elements considered as essential and embeds proliferation of centroblasts, point mutations of the corresponding antibody types represented in a shape space, differentiation to centrocytes, selection with respect to initial antigens, differentiation of positively selected centrocytes to plasma or memory cells and recycling of centrocytes to centroblasts. We use exclusively parameters with a direct biological interpretation such that, once determined by experimental data, the model gains predictive power. Based on the experiment of Han et al. (1995b) we predict that a high rate of recycling of centrocytes to centroblasts is necessary for the germinal center reaction to work reliably. Furthermore, we find a delayed start of the production of plasma and memory cells with respect to the start of point mutations, which turns out to be necessary for the optimization process during the germinal center reaction. The dependence of the germinal center reaction on the recycling probability is analysed.


The Application of Current Proposed Venous Thromboembolism Risk Assessment Model for Ambulatory Patients With Cancer.
Venous thromboembolism (VTE) is a commonly encountered problem in patients with cancer. In recent years, cancer treatment paradigm has shifted with most therapy offered in ambulatory outpatient settings. Excess of half VTEs in patients with cancer occur in outpatient settings without prior hospitalization, where current practice guidelines do not recommend routine prophylaxis. Risk assessment models (RAMs) for VTE in such patients were recently introduced. This study aims to assess the practical application of one of these models in clinical practice. Medical records and hospital electronic database were searched for patients with cancer having VTE. Known risk factors were collected, and risk assessment was done using the Khorana RAM. Over a 10-year period, 346 patients developed VTE in ambulatory settings. Median age was 57 and 59.0% were females. Lower extremities were involved in 196 (56.6%), while 96 (27.7%) had pulmonary embolism. Most (76.6%) patients had stage IV disease, only 9.0% had stage I or II disease. Only 156 (45.1%) patients were on active chemotherapy, for whom Khorana risk assessment score was calculated. In these patients, high risk was identified in 31 (19.9%) patients, while 81 (51.9%) had intermediate risk and 44 (28.2%) had low risk. No patients were on prophylaxis prior to VTE. Most ambulatory patients with cancer who developed VTE were not on chemotherapy, and many of those who were on active treatment had low Khorana risk scores. This illustrates the need to modify the model or develop a new one that takes into consideration this group of patients.


Hysteresis Thermodynamics of Capillary Condensation in Mesopores
A thermodynamic approach based on mass, energy, and entropy balances is developed for capillary condensation hysteresis in porous media. Processes of fluid condensation and evaporation are considered as quasi-isothermal irreversible transitions between equilibrium states of the capillary system. The corresponding balances express the equilibrium interfacial properties of the system through the work and heat measured in capillary process and, thus, may be used for evaluating the vapor-condensed phase interface area as a function of pressure, surface area of the porous solid, its pore size distribution, and surface fractal properties. Copyright 1997 Academic Press. Copyright 1997Academic Press


Melatonin as a therapeutic agent in experimental endotoxic shock.
We demonstrated that the pineal neurohormone melatonin exerts immunoregulatory effects via T-helper 2 (Th2) cell products. Th2 products may modulate the secretion and/or action of inflammatory cytokines, which play an important role in the development of septic shock associated with endotoxemia. Here we report that a single melatonin injection protects mice treated with a lethal dose of lipolysaccharide (LPS) especially when melatonin was injected 3 to 6 hr after LPS. This effect did not apparently involve Th cells or inhibition of inflammatory cytokines or macrophage nitric oxide (NO) generation. Nevertheless, plasma nitrate concentration, which reflects the rate of NO synthesis, showed a significant reduction at 18 and 24 hr after LPS administration. Melatonin is being studied in humans for cancer immunotherapy. The data presented here identify melatonin as potential therapy for septic shock.


Effects of eosinophil granule major basic protein on phosphatidylcholine secretion in rat type II pneumocytes.
Eosinophils are involved in inflammatory diseases such as asthma. We previously reported that activated eosinophils increased the phosphatidylcholine (PC) secretion in primary cultures of rat type II pneumocytes. Increased PC secretion was confirmed to be partly mediated by superoxide anions released from activated eosinophils. However, the influence of eosinophil granule proteins on PC secretion is unknown at present. In this study, we determined whether eosinophil major basic protein (MBP) influences PC secretion. MBP dose dependently increased the PC secretion in rat type II pneumocytes without producing any cell damage. The MBP-induced increase in PC secretion was significantly reduced by preadministration of either H-7, a protein kinase inhibitor, or 1, 2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, a chelator of intracellular Ca2+, but not by H-89, a protein kinase inhibitor. Our results suggest that the MBP-induced increase in PC secretion may provide mechanical stability and protect against lung atelectasis.


Application of a Silicone Sheet in Negative-Pressure Wound Therapy to Treat an Abdominal Wall Defect after Necrotizing Fasciitis.
Necrotizing fasciitis (NF) is an aggressive soft-tissue infection involving the deep fascia and is characterized by extensive deterioration of the surrounding tissue. Immediate diagnosis and intensive treatment, including debridement and systemic antibiotics, represent the most important factors influencing the survival of NF patients. In this report, we present a case of NF in the abdomen due to an infection caused by a perforated small bowel after abdominal liposuction. It was successfully treated using negative-pressure wound therapy, in which a silicone sheet functioned as a barrier between the sponge and internal organs to protect the small bowel.


Chemotaxonomic Classification of Peucedanum japonicum and Its Chemical Correlation with Peucedanum praeruptorum, Angelica decursiva, and Saposhnikovia divaricata by Liquid Chromatography Combined with Chemometrics.
The roots of Peucedanum japonicum (Apiaceae) have been used as an alternative to the roots of Saposhnikovia divaricata (Apiaceae) to treat common cold-related symptoms in Korea. However, a variety of Peucedanum species, including the roots of P. praeruptorum or Angelica decursiva (=P. decursivum), have been used to treat phlegm-heat-induced symptoms in China. Hence, as there are differences in the medicinal application of P. japonicum roots between Korea and China, chemotaxonomic classification of P. japonicum was evaluated. Sixty samples derived from P. japonicum, P. praeruptorum, A. decursiva, and S. divaricata were phylogenetically identified using DNA barcoding tools, and chemotaxonomic correlations among the samples were evaluated using chromatographic profiling with chemometric analyses. P. japonicum samples were phylogenetically grouped into the same cluster as P. praeruptorum samples, followed by S. divaricata samples at the next cluster level, whereas A. decursiva samples were widely separated from the other species. Moreover, P. japonicum samples showed higher chemical correlations with P. praeruptorum samples or A. decursiva samples, but lower or negative chemical correlations with S. divaricata samples. These results demonstrate that P. japonicum is more genetically and chemically relevant to P. praeruptorum or A. decursiva and, accordingly, the medicinal application of P. japonicum might be closer to the therapeutic category of these two species than that of S. divaricata.


Raspberry seeds extract selectively inhibits the growth of human lung cancer cells in vitro.
This study was focused on in vitro cytotoxicity screening of the raspberry seeds methanol extract towards a number of cancer cell lines of human origin. The tested extract at the preferred concentrations (IC50 <30 µg/mL) inhibited only the growth of the lung cancer A-549 cells (IC50 = 14.07 ± 0.96 µg/mL). At the same time, it was practically inactive (IC50 >300 µg/mL) and non-mutagenic towards normal MRC-5 lung cells. Finally, the extract potently scavenged both OH· (IC50 = 20.11 ± 1.77 µg/mL) and O2-· (IC50 = 47.23 ± 3.82 µg/mL), the free radicals of proved relevance for cancer pathophysiology. Though seeds were enriched with phenolic compounds (TPC = 5.21 ± 0.07 mg GAE/g), anthocyanins were present in traces only (TAC = 0.07 ± 0.003 mg cyn-3-glu/g), while flavonoids were not detected at all. This is the first report on anti-lung cancer potential of the seeds of any soft fruit.


Increase in pelvic floor muscle activity after 12 weeks' training: a randomized prospective pilot study.
To compare electromyography-assisted biofeedback training to pelvic floor muscle training (PFMT) alone in patients with female stress urinary incontinence. A prospective randomized pilot study was conducted between March 1998 and February 2000 at the university hospital for outpatient care. Participants were women with urodynamically tested stress incontinence aged 31 to 69 years without previous incontinence operations, 30 volunteers altogether. The biofeedback group received an electromyography-guided biofeedback device for home training and the PFMT-alone group trained without any device at home. All patients were advised to practice for 20 minutes per day five times a week for 12 weeks. According to the data analysis, muscle forces increased significantly in both supine (P <0.001) and standing (P <0.001) positions. In the supine position, the increase was significantly higher in the biofeedback group (P = 0.024). The results showed close to a significant decrease in the leakage index in the biofeedback group (P = 0.068), but in the PFMT-alone group, no change occurred. With respect to the pad test, the decrease was significant, but it was the same for both groups (P = 0.907). The findings of this study show that pelvic floor muscle activity is increased and the amount of leaked urine is decreased after 3 months of PFMT. These preliminary results show a significant improvement compared with the PFMT-alone group in PFMT outcome measures in patients using electromyography-assisted biofeedback training.


[The cytological aspects of chronic pancreatitis].
Biopsy material of pancreatic tissue using light-optical radioautography and electron microscopy, and the method of high-precise radioautography also, was investigated to study up the pancreatic gland (PG) pathology in chronic pancreatitis (CHP). It was established that CHP is a chronic proliferative-destructive process causing focal generalized fibrosis of PG. All the structural components of organ, and the duct epithelium first of all, are affected in CHP. It gives reason to regard a duct system as a complex independent morphofunctional unit of PG.


Construction and Characterization of a Synergistic lncRNA-miRNA Network Reveals a Crucial and Prognostic Role of lncRNAs in Colon Cancer.
Non-coding RNAs such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been found to be indispensable factors in carcinogenesis and cancer development. Numerous studies have explored the regulatory functions of these molecules and identified the synergistic interactions among lncRNAs or miRNAs, while those between lncRNAs and miRNAs remain to be investigated. In this study, we constructed and characterized an lncRNA-miRNA synergistic network following a four-step approach by integrating the regulatory pairs and expression profiles. The synergistic interactions with more shared regulatory mRNAs were found to have higher interactional intensity. Through the analysis of nodes in the network, we found that lncRNAs played roles that are more central and had similar synergistic interactions with their neighbors when compared with miRNAs. In addition, known colon adenocarcinoma (COAD)-related RNAs were found to be enriched in this synergistic network, with higher degrees, betweenness, and closeness. Finally, we proposed a risk score model to predict the clinical outcome for COAD patients based on two prognostic hub lncRNAs, MEG3 and ZEB1-AS1. Moreover, the hierarchical networks of these two lncRNAs could contribute to the understanding of the biological mechanism of tumorigenesis. For each lncRNA-miRNA interaction in the hub-related subnetwork and two hierarchical networks, we performed RNAup method to evaluate their binding energy. Our results identified two important lncRNAs with prognostic roles in colon cancer and dissected their regulatory mechanism involving synergistic interaction with miRNAs.


Blockchain distributed ledger technologies for biomedical and health care applications.
To introduce blockchain technologies, including their benefits, pitfalls, and the latest applications, to the biomedical and health care domains. Biomedical and health care informatics researchers who would like to learn about blockchain technologies and their applications in the biomedical/health care domains. The covered topics include: (1) introduction to the famous Bitcoin crypto-currency and the underlying blockchain technology; (2) features of blockchain; (3) review of alternative blockchain technologies; (4) emerging nonfinancial distributed ledger technologies and applications; (5) benefits of blockchain for biomedical/health care applications when compared to traditional distributed databases; (6) overview of the latest biomedical/health care applications of blockchain technologies; and (7) discussion of the potential challenges and proposed solutions of adopting blockchain technologies in biomedical/health care domains.


[Successful percutaneous angioplasty of renal artery in a patient with severe arterial hypertension and symptoms of hyperaldosteronism: a case report].
Arterial hypertension may result from renal artery stenosis. In this type of hypertension renin-angiotensin-aldosterone system is activated and patients often produce signs of hyperaldosteronism. It must be distinguished from primary hyperaldosteronism in order to chose a proper therapy. In this paper we describe a case of a 65-years-old man with severe arterial hypertension, which was difficult to control pharmacologically. The patient revealed symptoms which suggested primary hyperaldosteronism (except normal plasma renin activity). Only imaging techniques allowed diagnose of renal artery stenosis and carry out successful percutaneous angioplasty of renal artery.


The Influence of Different Bleaching Protocols on Dentinal Enzymatic Activity: An In Vitro Study.
This study aimed to investigate matrix metalloproteinase (MMP) activity in human dentin using in-situ and gelatin zymography, after at-home and in-office bleaching, related to their clinical exposure times. Dentin specimens (n = 5) were treated with 35% hydrogen peroxide (50 min per session/4 sessions), 10% carbamide peroxide (180 min/21 sessions), or no treatment. All were subjected to in-situ zymography. Dentin slices were, subsequently, obtained, covered with fluorescein-conjugated gelatin, and examined with confocal laser-scanning microscopy. The fluorescence intensity was quantified and statistically analyzed using one-way ANOVA and Bonferroni tests (α = 0.05). Furthermore, gelatin zymography was performed on protein extracts obtained from dentin powder (N = 8 teeth), treated with hydrogen peroxide or carbamide peroxide, with different exposure times (10/50 min for hydrogen peroxide; 252/1260 min for carbamide peroxide). The results of the in-situ zymography showed no statistical differences between the bleached specimens and the control group, with a medium level of gelatinolytic activity expressed in the dentin tubules. The results of gelatin zymography showed an increased expression of pro-MMP-9 in carbamide peroxide groups. The expression of pro-MMP-2 decreased in all the experimental groups. The bleaching treatments performed on the enamel of sound teeth do not influence dentinal enzymatic activity. However, when unprotected dentin tissue is bleached, matrix metalloproteinases are more expressed, particularly when carbamide peroxide is used, proportional to the exposure time.


A cholesterol-lowering diet does not produce adverse psychological effects in children: three-year results from the dietary intervention study in children.
The Dietary Intervention Study in Children (DISC), a 2-arm, multicenter intervention study, examined the efficacy and safety of a diet lower in total fat, saturated fatty acids, and cholesterol than the typical American child's diet. A total of 663 8- to 10-year-old children with elevated low-density lipoprotein cholesterol levels were randomly assigned to either an intervention or a usual-care group. Intervention included group and individual counseling sessions to assist participants in adopting a dietary pattern containing 28% or less of calories from total fat (<8% as saturated fat, up to 9% as polyunsaturated fat, and 11% as monounsaturated fat) and dietary cholesterol intake of less than 75 mg/1,000 kcal. The dietary intervention reduced low-density lipoprotein cholesterol levels, and 3-year results showed no adverse effects for children in the intervention group in terms of academic functioning, psychological symptoms, or family functioning.


New insights into pediatric rhinosinusitis.
Rhinosinusitis is a common children's disease. Most cases are acute, follow an episode of common cold, and are the consequence of a superimposed bacterial infection. If mild, they are characterized by the persistence of signs and symptoms of upper respiratory tract disease for more than 10 days; if severe, they involve fever and a purulent nasal discharge, and can cause a substantial decline in general health. Recurrent acute or chronic cases are usually diagnosed in children with predisposing factors, such as recurrent respiratory tract infections, allergic rhinitis, cystic fibrosis, immunodeficiency, ciliary dyskinesia, anatomic abnormalities or reflux. Therapy is based on antibiotics, administered orally in mild, and intravenously in severe cases. On the basis of recently highlighted antibiotic resistances and the possibility of spontaneous resolution, experts agree in considering amoxicillin the drug of choice for mild cases, and an antibiotic capable of overcoming all possible resistance for severe cases.


The information content of tensile tests of human hair (wet) is limited: Variables mainly cluster in just two principal components.
Tensile testing of keratin fibres, such as wool and hair, in the wet state is a well established tool in the academic as well as applied portfolio of mechanical analyses. For the tensile curve of a hair fibre, fourteen material-specific stress-, strain, and work-related variables were identified. Analysing twelve samples of cosmetically untreated hair, we show that the variables show good precision and a satisfactory degree of homogeneity across samples. Correlation analysis shows strong relationships between essentially all variables. Some strong correlations were in fact expected. However, their actual extent is very surprising, including even rather dissimilar variables (e.g., elastic-vs break-modulus). This observation led us to investigate whether variables may be clustered into a number of groups in order to define a set of underlying orthogonal factors, using Factor Analysis. The results show that 87% of data variance can be accounted for by just two factors, which we refer to as 'stress-' and 'strain'- factor, respectively. The tensile properties of untreated hair (wet) are thus well described by just any pair of strong variables from each factor, such as elastic modulus and break strain. We hypothesize that similar principles may also be applicable for treated hair. This type of approach and its implications may also have relevance for other epidermal appendages (nails, claws, horn, etc) or even more generally for other biological composite materials, such as skin, tendon and bone.


Postoperative pharmacokinetics of meloxicam in horses after surgery for colic syndrome.
NSAIDs are often used in horses with colic syndrome during the postoperative period, due to their ability to contrast endotoxemia and to promote an analgesic and anti-inflammatory effect. As the pharmacokinetics of a drug are often modified in unhealthy animals compared to healthy subjects, the aim of this study was to evaluate the pharmacokinetic profile of meloxicam after i.v. administration in horses undergoing laparotomy for colic syndrome. Eight horses received 0.6 mg/kg of meloxicam i.v. towards the end of surgery. Blood samples were taken at scheduled time points during the following 24 hr. The serum concentration of the drug was determined by HPLC. Terminal half-life (6.88 ± 2.96 hr), volume of distribution at steady-state (186.53 ± 61.20 ml/Kg) and clearance (27.91 ± 5.72 ml kg-1 hr-1 ) were similar to those reported in literature for healthy horses. This result suggests that no adjustment of the approved dose should be necessary when meloxicam is used to treat horses in the immediate postoperative period after surgery for colic syndrome.


Zoonotic Cryptosporidium spp. in Wild Rodents and Shrews.
There has been a significant increase in the number of reported human cryptosporidiosis cases in recent years. The aim of this study is to estimate the prevalence of Cryptosporidium spp. in wild rodents and shrews, and investigate the species and genotype distribution to assess zoonotic risk. Partial 18S rRNA gene nested-PCR reveals that 36.8, 53.9 and 41.9% of mice, voles and shrews are infected with Cryptosporidium species. The highest prevalence occurred in the Microtus agrestis (field vole) and Myodes glareolus (bank vole). Interestingly, bank voles caught in fields were significantly more often Cryptosporidium-positive compared to those caught in forests. The proportion of infected animals increases from over-wintered (spring and summer) to juveniles (autumn) suggesting acquired immunity in older animals. Based on Sanger sequencing and phylogenetic analyses, Apodemus flavicollis (yellow-necked mouse) is commonly infected with zoonotic C. ditrichi. Voles carry multiple different Cryptosporidium sp. and genotypes, some of which are novel. C. andersoni, another zoonotic species, is identified in the Craseomys rufocanus (grey-sided vole). Shrews carry novel shrew genotypes. In conclusion, this study indicates that Cryptosporidium protozoan are present in mouse, vole and shrew populations around Finland and the highest zoonotic risk is associated with C. ditrichi in Apodemus flavicollis and C. andersoni in Craseomys rufocanus. C. parvum, the most common zoonotic species in human infections, was not detected.


TrkB antibody elicits cytotoxicity and suppresses migration/invasion of transitional cell carcinoma cells.
BDNF (brain-derived neurotrophic factor) and its receptor TrkB (tropomyosin receptor kinase B) play important roles in the progression of cancer, including transitional cell carcinoma (TCC) cells reported in our previous investigation. In this study, we used a specific TrkB antibody (Ab) to evaluate its effects on survival, proliferation and migration/invasion in three TCC cell lines (BFTC905, T24 and TSGH8301) in vitro. The TrkB Ab at 1 and 3 microg/ml, but not the TrkA or TrkC Abs, significantly elicited cytotoxicity in TCC cells. The TrkB Ab at 3 microg/ml also induced apoptosis of TCC cells, which may result from up-regulation of phospho-p38 plus down-regulation of survivin and securin expression. The TrkB Ab at 0.5 microg/ml, which did not show cytotoxicity, suppressed migration of TCC cells and invasion of BFTC905 cells, possibly mediated through increased E-cadherin, decreased BDNF-stimulated phospho-PLCgamma1 and reduced MMP-9 activity. These results indicate that TrkB blockade may be a new strategy for TCC therapy.


Operational Spectroelectrochemical Investigation on the Interfacial Charge Dynamics of Copper Bismuth Oxide Based Photocathode.
Copper bismuth oxide (CBO) is an emerging photocathode in photoelectrochemical (PEC) water splitting but exhibits limited performance due to the severe recombination of photogenerated charges at the semiconductor-liquid junction (SCLJ). For the first time, a set of operational spectroelectrochemical experiments including electrochemical impedance spectroscopy (EIS), transient photocurrent spectroscopy (TPS), and intensity-modulated photocurrent/voltage spectroscopy (IMVS, IMPS) are designed to investigate the charge dynamics at the SCLJ. It is indicated that there are dense surface states above the valence band of CBO, inducing the "Fermi level pinning" (FLP) effect at the SCLJ. The kinetic parameters speculated by IMVS and IMPS indicate the charge transfer efficiency of below 10% with even a bias of ∼0.7 V applied. TPS confirms the sluggish dynamics because of the charging behavior of the surface states. It is expected that this work would provide new connotations of charge dynamics at the SCLJ for the further optimization of CBO-based PEC systems.


[Effect of aspirin on breast cancer stem cells and stemness of breast cancer].
Objective: To explore the effect of aspirin on the stemness of breast cancer cells and apoptosis induction of breast cancer stem cells. Methods: The 4T1 cells cultured with stem cell culture medium were screened, and immunofluorescence technique, flow cytometry and tumor-forming experiment in vivo were applied to test stem cell characteristics of the tumor spheres. After dealt with aspirin, the apoptosis rate of 4T1 stem cells was analyzed by flow cytometry. The 4T1 cells were cultured in vitro and treated with aspirin, then flow cytometry analysis was used to detect the expression of aldehydedehy drogenase1 (ALDH1), and the expression of stemness genes was tested by Western blot . Then, after culturing the cells with medium containing basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), B27 and N2, the ability of sphere-forming was observed and recorded by microscopy. In vivo BALB/c mice inoculated with 4T1 stem cells were randomly divided into the control group, 10 mg/kg, 30 mg/kg and 100 mg/kg aspirin groups. After 10 days, the mice were dealt with aspirin or NS for 15 days, then the tumor growth was observed and recorded. Results: The ratio of ALDH1 positive cells was up to 78.55%, and 4T1 tumor sphere had a postive expression of ALDH1 and sex determining region Y-box 2 (SOX2). In vivo tumorigenesis abilities of tumor sphere with 1×10(2) 4T1 stem cells could be 75%, while the ratio of normal cells was zero. The ratio of Aspirin-induced apoptosis of 4T1 stem cells at early stage and and late stage increased from 0.36% to 21.61%, and from 4.21% to 21.38%, respectively. Flow cytometry and Western blot assay results indicated that aspirin could reduce the expression of ALDH1, SOX2, octamer-binding transcription factor 4 (OCT4) and NANOG in 4T1 cells. Sphere-forming experiments results showed that aspirin could inhibit sphere forming ability of breast cancer cells. In vivo, aspirin inhibited the growth of tumors with a dose-dependent manner. Conclusion: Aspirin could induce apoptosis of cancer stem cells and reduce stemness of breast cancer, and thus play a growth-inhibiting action on breast cancer.


Temperature dependence of chlorophyll a fluorescence in relation to the physical phase of membrane lipids algae and higher plants.
The temperature dependence of the yield of chlorophyll a fluorescence was measured at room temperatures in living algal cells and higher plant chloroplasts. 3-(3',4'-Dichlorophenyl)-1, 1-dimethylurea was added to the samples during the measurements in order to eliminate the influence of photosynthetic photochemical reactions on the fluorescence yield.In Anacystis nidulans the maximum in the curve for the fluorescence yield versus temperature occurred near the temperatures at which the transition of physical phase of the membrane lipids changes from the liquid crystalline to the mixed solid-liquid crystalline states. These findings suggest that the occurrence of a fluorescence maximum in the temperature-dependence curve is an indication of the thermal transition of physical phase of membrane lipids. Similar but less distinct maxima were found in Cyanidium caldarium and Euglena gracilis. No maxima were seen in the curves for chlorophyll a fluorescence versus temperature in Chlorella pyrenoidosa, Plectonema boryanum, Stichococcus bacillaris Phaeodactylum tricornutum, or in chloroplasts of the higher plants, spinach, lettuce, tomato, and Tidestromia oblongifolia.The fluorescence yield of allophycocyanin in Anacystis did not show such a maximum, but did show a steep increase with decreasing temperature below 5 C. the fluorescence yields of chlorophyll a and phycobilins extracted from Anacystis increased monotonously with decreasing temperature.


Neurofibromatosis type 1 and infantile spasms.
There is no agreement on the prevalence, natural history and outcome of infantile spasms (IS) in neurofibromatosis type 1 (NF1). By contrast, its prevalence and outcome are well characterised in the setting of other neurocutaneous disorders (e.g. tuberous sclerosis). The aim of the present study was to try to establish a genotype-phenotype correlation in IS in the setting of NF1. A retrospective (years 1990-2000) and prospective (years 2000-2006) study in three paediatric centres in Italy were taken as referral populations for: (1) children with NF1 and (2) neurological problems in childhood. Ten NF1 patients have had IS. The calculated population-based: (1) prevalence of IS in NF1 (0.76%) was higher than the reported frequency of IS in the general population (0.02-0.05%) and (2) frequency of NF1 in the IS series in two out of three centres (0.62-0.90%) was lower than the estimated frequencies in the literature (1.5-3.0%). Patients had psychomotor delay preceding the spasms (50%), symmetrical spasms (50%), typical (80%) and modified (20%) hypsarrhythmia and foci of spikes and waves and a good response to corticosteroid treatment (50%). Outcome was good in 30%. Imaging revealed high-signal foci in atypical locations (sub-cortical and central brain regions). Deoxyribonucleic acid analysis revealed three novel NF1 gene mutations without genotype-phenotype correlation. Even though the combination of IS and NF1 does not seem to be coincidental, it is certainly an unusual event in NF1--rarer than in other neurocutaneous disorders. Spasms in NF1 are not associated with specific genetic defects.


Regulation of electromotility in the cochlear outer hair cell.
Mechanosensory outer hair cells play an essential role in the amplification of sound-induced vibrations within the mammalian cochlea due to their ability to contract or elongate following changes of the intracellular potential. This unique property of outer hair cells is known as electromotility. Selective efferent innervation of these cells within the organ of Corti suggests that regulation of outer hair cell electromotility may be the primary function of the efferent control in the cochlea. A number of studies demonstrate that outer hair cell electromotility is indeed modulated by the efferent neurotransmitter, acetylcholine. The effects of acetylcholine on outer hair cells include cell hyperpolarization and a decrease of the axial stiffness, both mediated by intracellular Ca(2+). This article reviews these results and considers other potential mechanisms that may regulate electromotility, such as direct modification of the plasma membrane molecular motors, alteration of intracellular pressure, and modification of intracellular chloride concentration.


Interaction of 3,4-methylenedioxymethamphetamine and methamphetamine during metabolism by in vitro human metabolic enzymes and in rats.
Illicit amphetamine-type stimulant (ATS) tablets commonly contain one or more active ingredients, which have hallucinogenic and/or stimulant effects. Because components such as 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (MA) in ATS tablets have similar chemical structures, they could be metabolized by common metabolic enzymes. To investigate potential metabolic interactions of ATS tablet components, we studied the in vitro metabolism of MDMA and MA using human metabolic enzymes. MDMA and MA were mainly metabolized by cytochrome P450 2D6 (CYP2D6) and mutually inhibited the production of their main metabolites. In vivo experiments were also performed using intravenous administration of MDMA, MA, or their mixture to rats. The plasma concentrations of MDMA and MA after co-administration were higher than those after administration of MDMA or MA alone. The results in this study imply that multiple components in ATS tablets can interact to mutually inhibit their metabolism and potentially enhance the toxicity of each component.


Genetic and environmental determinants of level of pulmonary function.
Measurements of level of pulmonary function (one second forced expiratory volume (FEV1) and forced expiratory flow between the 25% and 75% volume points (FEF 25-75)) were obtained on members of 404 nuclear families living in East Boston, Massachusetts in 1974. These families were ascertained through a random sample of children aged 5-9 years. Measurements were obtained on family members on three separate occasions during a 5-year period. These data were subjected to the techniques of path analysis to study the relative contributions of heredity and environment to individual levels of pulmonary function. Genetic heritability was found to be consistent through time (41-47%) and was the same for parents and their children. Common familial environmental effects on level of pulmonary function explained 1-4% of the variability in children and 11-28% in adults. Furthermore, we were able to confirm prior epidemiologic analysis of these data which have demonstrated an effect of maternal smoking on the level of pulmonary function in their children.


Importance of surface diffusivities in pesticide adsorption kinetics onto granular versus powdered activated carbon: experimental determination and modeling.
Three pesticides (atrazine, bromoxynil and diuron) and two granular activated carbons are involved in equilibrium and kinetic adsorption experiments. Equilibrium is represented by Freundlich isotherm law and kinetic is described by the Homogeneous Surface Diffusion Model, based on external mass transfer and intraparticle surface diffusion. Equilibrium and long-term experiments are conducted to compare Powdered Activated Carbon and Granular Activated Carbon. These first investigations show that crushing GAC into PAC improves the accessibility of the adsorption sites without increasing the number of these sites. In a second part, kinetics experiments are carried out using a Differential Column Batch Reactor. Thanks to this experimental device, the external mass transfer coefficient k(f) is calculated from empirical correlation and the effect of external mass transfer on adsorption is likely to be minimized. In order to obtain the intraparticle surface diffusion coefficient D. for these pesticides, comparisons between experimental kinetic data and simulations are conducted and the best agreement leads to the Ds coefficient. This procedure appears to be an efficient way to acquire surface diffusion coefficients for the adsorption of pesticides onto GAC. Finally it points out the role of surface diffusivity in the adsorption rate. As a matter of fact, even if the amount of the target-compound that could be potentially adsorbed is really important, its surface diffusion coefficient may be small, so that its adsorption may not have enough contact time to be totally achieved.


The risk of suicide among wounded Vietnam veterans.
This study was undertaken to determine whether an association exists between combat trauma and risk of postservice suicide among Vietnam veterans. Risk of suicide for 34,534 veterans who were wounded in Vietnam was evaluated for severity of wound and number of times wounded. There was a trend of increasing risk of suicide with increased occurrence of combat trauma, the highest relative risk (1.82, 95% confidence interval [CI] = 1.12, 2.96) being observed for those veterans who were wounded more than once and hospitalized for a wound. In comparison with the US male general population, veterans hospitalized because of a combat wound or wounded more than once had a significantly increased risk of suicide (standardized mortality ratios [SMRs] of 1.22 [95% CI = 1.00, 1.46] and 1.58 [95% CI = 1.06, 2.26], respectively). Those wounded more than once and hospitalized had the highest increased risk of suicide (SMR = 1.73, 95% CI = 1.10, 2.60). This study suggests that, among wounded Vietnam veterans, there is an increased risk for suicide associated with increased occurrence of combat trauma.


Virulence Factor Identification in the Banana Pathogen Dickeya zeae MS2.
The phytopathogen Dickeya zeae MS2 is a particularly virulent agent of banana soft rot disease. To begin to understand this banana disease and to understand the role of quorum sensing and quorum-sensing-related regulatory elements in D. zeae MS2, we sequenced its genome and queried the sequence for genes encoding LuxR homologs. We identified a canonical LuxR-LuxI homolog pair similar to those in other members of the genus Dickeya The quorum-sensing signal for this pair was N-3-oxo-hexanoyl-homoserine lactone, and the circuit affected motility, cell clumping, and production of the pigment indigoidine, but it did not affect infections of banana seedlings in our experiments. We also identified a luxR homolog linked to a gene annotated as encoding a proline iminopeptidase. Similar linked pairs have been associated with virulence in other plant pathogens. We show that mutants with deletions in the proline iminopeptidase gene are attenuated for virulence. Surprisingly, a mutant with a deletion in the gene encoding the LuxR homolog shows normal virulence.IMPORTANCEDickeya zeae is an emerging banana soft rot pathogen in China. We used genome sequencing and annotation to create an inventory of potential virulence factors and virulence gene regulators encoded in Dickeya zeae MS2, a particularly virulent strain. We created mutations in several genes and tested these mutants in a banana seedling infection model. A strain with a mutated proline iminopeptidase gene, homologs of which are important for disease in the Xanthomonas species phytopathogens, was attenuated for soft rot symptoms in our model. Understanding how the proline iminopeptidase functions as a virulence factor may lead to insights about how to control the disease, and it is of general importance as homologs of the proline iminopeptidase occur in dozens of plant-associated bacteria.