Dengue infection: Global importance, immunopathology and management.
Dengue is an arboviral infection that is hyperendemic in tropical and subtropical climates. Clinical manifestations of dengue can range from asymptomatic infection to severe infection with multi-organ failure. Dengue haemorrhagic fever (DHF) is a subcategory in dengue infection with a hallmark of plasma leak (ie critical phase). The plasma leak in DHF is selective (pleuroperitoneal spaces), transient and dynamic, and needs careful monitoring and meticulous fluid resuscitation. In addition, dengue fever may present with extended and unusual manifestations affecting any organ, including the heart, liver, kidney and brain. Studies on vaccine development and vector control are ongoing to prevent this infection of global importance. In this article, the clinicopathological features and management aspects of dengue are discussed.


Taste Receptors: Regulators of Sinonasal Innate Immunity.
Taste receptors in the oral cavity guide our preferences for foods, preventing toxic ingestions and encouraging proper nutrient consumption. More recently, expression of taste receptors has been demonstrated in other locations throughout the body, including the airway, gastrointestinal tract, pancreas, and brain. The extent and specific roles of "extraoral" taste receptors are largely unknown, but a growing body of evidence suggests that taste receptors in the airway serve a critical role in sensing bacteria and regulating innate immunity. This review will focus on the function of bitter and sweet taste receptors in the human airway with particular emphasis on T2R38, a bitter taste receptor found in sinonasal ciliated cells, and bitter and sweet receptors found on specialized sinonasal solitary chemosensory cells. The importance of these novel taste receptor-immune circuits in the human airway and their clinical relevance in airway disease will also be reviewed.


Chiral structure determination of aligned single-walled carbon nanotubes on graphite surface.
Chiral structure determination of single-walled carbon nanotube (SWNT), including its handedness and chiral index (n,m), has been regarded as an intractable issue for both fundamental research and practical application. For a given SWNT, the n and m values can be conveniently deduced if an arbitrary two of its three crucial structural parameters, that is, diameter d, chiral angle θ, and electron transition energy E(ii), are obtained. Here, we have demonstrated a novel approach to derive the (n,m) indices from the θ, d, and E(ii) of SWNTs. Handedness and θ were quickly measured based on the chirality-dependent alignment of SWNTs on graphite surface. By combining their measured d and E(ii), (n,m) indices of SWNTs can be independently and uniquely identified from the (θ,d) or (θ,E(ii)) plots, respectively. This approach offers intense practical merits of high-efficiency, low-cost, and simplicity.


[Three nonparallel screws for the treatment of femoral neck fractures].
To explore clinical effects of three nonparallel screws in treating femoral neck fractures. From September 2008 and May 2009, 29 patients were treated, including 12 males and 17 females with an average age of 52 years (ranged from 27 to 62 years). Before operation, according to Garden classification system, 2 cases were Garden type II (undisplaced fracture), 18 cases were Garden type III (partial displaced fracture) and 9 cases were Garden type IV (complete displaced fracture). After fracture reduction in operation, Pauwels classification system was used to classify the type, and 12 cases were type II, 17 cases were type III Closed reduction and internal fixation with three non-parallel screws were used to treat. The surgery X-ray and follow-up X-ray were compared to observe whether femoral neck abbreviate and screw exit appeare. Harris scoring was used to evaluate function. All patients were followed-up from 34 to 44 months with an average of 38 months. The mean time of bone union was 7 (ranged, 3 to 12) months. Nonunion occured in 4 cases with Garden IV, and femoral head necrosis occurred in 2 cases. For Harris scoring, two cases with nondisplaced fracture were 100. Among 27 cases with displaced fractures, 23 cases achieved bone union without femoral head necrosis, average Harris scale was 91.35 +/- 8.00, and the average Harris scale of 4 cases with bone nonunion was 61.23 +/- 5.12. For all but one, there was no femoral neck crispation after bone union. Nonparallel screws for femoral neck fractures can effectively control abbreviation and screw tail exit after fracture healing.


Explaining the increased mortality in type 1 diabetes.
Despite large improvements in the management of glucose levels and in the treatment of cardiovascular risk factors, the mortality rate in individuals with type 1 diabetes (T1D) is still high. Recently, Lind et al found that T1D individuals with glycated hemoglobin levels of 6.9% or lower had a risk of death from any cause or from cardiovascular causes that is twice as high as the risk for matched controls. T1D is a chronic disease with an early onset (e.g., pediatric age) and thus in order to establish a clear correlation between death rate and the glycometabolic control, the whole history of glycemic control should be considered; particularly in the early years of diabetes. The switch from a normo- to hyperglycemic milieu in an individual with T1D in the pediatric age, represents a stressful event that may impact outcomes and death rate many years later. In this paper we will discuss the aforementioned issues, and offer our view on these findings, paying a particular attention to the several alterations occurring in the earliest phases of T1D and to the many factors that may be associated with the chronic history of T1D. This may help us to better understand the recently published death rate data and to develop future innovative and effective preventive strategies.


The cariostatic mechanism of fluoride.
The benefits of using fluoride to prevent caries have been known for many years, but a complete understanding of this mechanism is still being researched. The fluoride concentration in the apatitic structure of enamel does not have as significant an effect on reducing caries as a continuous presence of fluoride in the plaque liquid. Concentrated, topical fluoride agents (such as in toothpaste, fluoride mouth rinses, gels, or varnishes) have a different mechanism of fluoride protection than low-concentration applications (such as fluoridated water). In initial caries lesions and plaque, concentrated agents form globules of a calcium fluoride-like material on the enamel surface. This material is fairly insoluble, possibly because it is coated with phosphates or proteins. This mechanism explains how the topical application of a fluoride varnish, two or three times a year, can result in caries reduction.


Liver function during extracorporeal whole liver perfusion in a pig model of acute ischemic liver failure.
The shortage of livers for transplant has renewed interest in the potential of temporary liver support such as extra corporeal whole liver perfusion. In an ischemic induced liver failure model we perfused an extra corporeal liver through only a portal vein and assessed the function of this ex vivo liver by using hepatic tests to estimate elimination as well as synthesis capacities. Acute liver failure was performed in five control pigs by a hepatic devascularization associated to an end to side portocaval shunt. In a treated group, 5 to 6 h after this hepatic devascularization, animals were connected to an extra corporeal liver perfused via the portal vein with blood withdrawn from the ischemic liver animal from its portal vein. Devascularization of the liver induced an increase in liver enzymes and ammonia, a drop in the ratio of branched chain amino acids to aromatic amino acids, and a decrease in blood urea and indocyanine green and galactose clearances. In treated animals, urea, amino acid ratio, and clearances increased after the ex vivo liver perfusion. In this group, mean bile production and mean liver oxygen consumption were 13.7 +/- 3.6 ml/h and 16.1 +/- 7.7 ml/min, respectively. In an acute ischemic liver failure pig model, an extra corporeal whole liver perfusion demonstrated detoxification properties as well as synthesis capacities.


An emergent self-organizing map based analysis pipeline for comparative metabolome studies.
Modern high-throughput techniques allow for the identification and quantification of hundreds of metabolites ofa biological system which cover central parts of the metabolome. Due to the amount and complexity of obtained data there is an increasing need for the development of appropriate computational interpretation methods. A novel data analysis pipeline designed for high-throughput determined metabolomic data is presented. The combination of principal component analysis (PCA) with emergent self-organizing maps (ESOM) and hierarchical cluster analysis (HCA)algorithms is used to unravel the structure underlying metabolomic data sets, including the detection of outliers. Observed differences between various analyzed metabolomes are automatically mapped and visualized using KEGG metabolic pathway maps. This way typical metabolic biomarker for data sets from various analyzed growth conditions and genetic backgrounds become visible. In order to validate the described methods we analyzed time resolved metabolomic datasets obtained for Corynebacterium glutamicum cells grown on various carbon sources consisting of 126 different metabolic patterns. The analysis pipeline was implemented in the user-friendly Java software eSOMet. The software was successfully used for the clustering of the metabolome data mentioned above. Metabolic biomarkers typical for the utilized carbon sources and analyzed growth phases were identified.


Multifocal epithelial hyperplasia: a forgotten condition in the elderly.
Multifocal epithelial hyperplasia (MEH), also known as focal epithelial hyperplasia and Heck disease, is a relatively rare condition caused by the human papillomavirus. This case report describes a 92-year-old man who presented with multiple, asymptomatic, circumscribed, soft, flattened papules in different sizes on the retrocommissure of his lower lip. The lesions were of 2 months' duration and had the same coloration as the adjacent normal mucosa. Histopathologic examination showed orthokeratinized stratified squamous epithelium with acanthosis, some areas of club-shaped rete ridges, and a few superficial epithelial cells with koilocytic changes and a mitosoid-like appearance. A diagnosis of MEH was established. Although MEH tends to occur in the first 2 decades of life, it can be encountered in elderly patients as well.


Pacemaker stored electrograms: teaching us what is really going on in our patients.
Stored electrograms (EGMs), well-known diagnostic tools in implantable cardioverter defibrillators, have now been incorporated in pacemakers as well, thereby increasing their diagnostic capabilities. The clinician can detect and diagnose patient arrhythmias with EGMs and directly validate diagnostic data stored by the devices. The appropriateness of detection algorithms can also be judged. Initial experiences with pacemaker EGMs reveals their potential to detect and diagnose sensing or detection algorithm problems. These so-called "false-positive" EGMs help to optimize pacemaker programming. Date and time stamp can correlate an event to patient symptoms. Recent advances, like onset recordings and marker annotation, have further increased the effectiveness of stored EGMs. The use of patient-triggered magnet-stored EGMs facilitates diagnostic workups in symptomatic pacemaker patients and reveals nondevice related symptoms in a considerable number of cases. Stored EGMs in pacemakers will soon be a standard diagnostic tool that can illustrate what is really going on in our patients.


Approach to the study of neurophysiological mechanism of food motivation.
The present article estimates depolarization-polarization processes in the nerve tissue of afferent systems, including visceral ones, according to the changes of the direct current (DC) potential level. Food motivation is formed and satisfied concurrently with changes in the neocortex direct current potential level and a number of cerebral brain limbic structures in rats. Lateral hypothalamic nucleus, basolateral amygdala area, and auditory cortex in hungry rats have a more negative DC potential shift than in satisfied animals, while a reverse relation is observed in the ventromedial hypothalamic nucleus. The results obtained are considered an indication of polarization shifts in the mechanism of motivated and emotional behavior. An idea of the determining role of polarization processes in the mechanism of motivated and emotional behavior is developed.


Hybrid biosensor for the determination of lactose.
Genetically manipulated bacteria Escherichia coli K-12 recombinant PQ-37 and glucose oxidase (EC 184.108.40.206) were used for the construction of a hybrid lactose sensor because of the hyperproduction of beta-galactosidase (EC 18.104.22.168) by E. coli effected by a genotoxic agent. The biocatalytic layer was prepared by coimmobilization of the E. coli cells with glucose oxidase on the nylon network via glutardialdehyde and fixed to the Clark oxygen electrode. The influence of pH, temperature, and concentration of activators of beta-galactosidase on the sensor response was tested. Analyses of milk products were completed without any special pretreatment of the samples. The contents of lactose determined by hybrid sensor agree with conventional photometric measurements. Standard relative deviation is less than 3% for all samples. The half-life of operational stability is 30 days.


[Re-establishment of effective radiation dose to personnel of a radioactive waste utilizing plant].
The radiation dose of incorporated cesium-137 was estimated in the workers of a radioactive waste-utilizing plant. For this, methods were developed to retrospectively estimate the dose of internal radiation from the data available in the archives on the body's cesium levels obtained through mass indicator monitoring. The methods were based on the theoretical considerations and variations of inhaled radionuclide intake. The average rhythm of inhalant intake was restored by 891 measurements made in 490 workers to calculate radiation levels in 1977-1995. The individual effective doses of internal radiation of the staff with cesium-137, which were accumulated by 1995 in the persons who began to work at the plant in 1997, were no greater than 1437 muSv and failed to be as high as 1% of the maximum acceptable dose in all cases.


Investigating a pediatric hospital's response to an inpatient census surge during the 2009 H1N1 influenza pandemic.
On November 4, 2009, the 250-bed Seattle Children's Hospital (SCH) identified a surge in its census--245 inpatients, well above the average midnight census of 207. In response, SCH activated its pandemic influenza surge plan in an effort to decrease the inpatient census. Within 16 hours, 51 patients (20.4% of total bed capacity) had been discharged, and inpatient census at SCH decreased to 222 patients. As part of a quality improvement project, SCH's response to the surge was investigated, with data drawn from interviews, a review of records created in the course of the surge plan implementation, an e-mail survey of attending physicians responsible for patient discharges, and models examining predictors of hospital discharges. Analysis of three years of hospital data (2007-2009) indicated that the high census on November 4 was an uncommon but not unprecedented occurrence. In addition, there was a clear positive association between an evening's census and the number of discharges during the following 24 hours. SCH discharged essentially the same number of patients on November 4 as on previous high-census days when the surge plan was not activated, suggesting that the surge plan did not succeed in creating excess discharges. Increasingly, evidence indicates that care quality depends on the degree to which hospital resources are sufficient to meet demand. Reverse triage, at least as implemented by SCH on November 4, 2009, is unlikely to represent an effective solution to surge outside of a disaster setting because of its requirement for centralized decision making. SCH has incorporated the results of this review into the way that it collects and analyzes data, manages flow, and responds to inpatient surges.


Novel therapeutic modalities and drug delivery - erlotinib liposomes modified with galactosylated lipid: in vitro and in vivo investigations.
The aim of this study to develop galactosylated erlotinib liposomes for treatment of lung cancer. The liposomes were prepared by using solvent evaporation method. Various parameters such as particle size, zeta potential, entrapment efficiency, stability and in vitro drug release were determined. The size of liposomes (both conventional and modified) was 103.5 and 121.4 nm. The zeta potential and EE of both liposomes were -7.1 ± 1.3 mV, -1.2 ± 0.5 mV and (82.3 ± 1.9)%, (83.4 ± 1.5)%, respectively. It was found that modified liposomes increase the size of particles. The in vitro release results indicated that the release of erlotinib from galactosylated liposomes was similar to that of conventional liposome, demonstrating that the modification did not affect erlotinib release. From the result of in vivo, it proved that erlotinib liposomes can significantly improve the drug targeting, rapidly distribute the drug in the body, prolong the drug circulation time and significantly increase the relative bioavailability of the drug. Biodistribution studies showed that erlotinib from galactosylated liposomes had higher AUC inside liver than the injection group and no histological change occurred to the rat liver after the administration of erlotinib conventional and galactosylated liposomes.


Sol-gel derived nano-structured zinc oxide film for sexually transmitted disease sensor.
A 20-mer thiolated oligonucleotide probe (th-ssDNA) specific to Neisseria gonorrhoeae immobilized onto a sol-gel derived nano-structured zinc oxide (ZnO) film dip-coated onto an indium-tin-oxide (ITO) glass substrate has been used for the fabrication of a DNA biosensor for sexually transmitted disease (gonorrhoea) detection using hybridization technique. The results of characterization studies carried out on this th-ssDNA-ZnO/ITO bioelectrode using X-ray diffraction, UV-Visible, Fourier-transform infrared, scanning electron microscopy and electrochemical techniques reveal the linearity as 0.000524 fmol-0.524 nmol, with a detection limit of 0.000704 fmol within 60 s.


Self-compassion, pain, and breaking a social contract.
Self-compassion is the ability to respond to one's failures, shortcomings, and difficulties with kindness and openness rather than criticism. This study, which might be regarded as a proof-of-concept study, aimed to establish whether self-compassion is associated with expected emotional responses and the likelihood of responding with problem solving, support seeking, distraction, avoidance, rumination, or catastrophizing to unpleasant self-relevant events occurring in 3 social contexts. Sixty chronic pain patients were presented with 6 vignettes describing scenes in which the principal actor transgressed a social contract with negative interpersonal consequences. Vignettes represented 2 dimensions: (1) whether pain or a nonpain factor interrupted the fulfillment of the contract and (2) variation in the social setting (work, peer, and family). The Self-Compassion Scale was the covariate in the analysis. Higher levels of self-compassion were associated with significantly lower negative affect and lower reported likelihood of avoidance, catastrophizing, and rumination. Self-compassion did not interact with pain vs nonpain factor. Work-related vignettes were rated as more emotional and more likely to be associated with avoidance, catastrophizing, and rumination and less likelihood of problem solving. The findings suggest that self-compassion warrants further investigation in the chronic pain population both regarding the extent of its influence as a trait and in terms of the potential to enhance chronic pain patients' ability to be self-compassionate, with a view to its therapeutic utility in enhancing psychological well-being and adjustment. Limitations regarding the possible criterion contamination and the generalizability of vignette studies are discussed.


Prognosis and outcome of non-Hodgkin lymphoma in primary Sjögren syndrome.
Sjögren syndrome (SS) has been associated with the development of non-Hodgkin lymphoma (NHL). From a cohort of 584 SS patients followed in our department from 1980 to 2010, we retrospectively analyzed 53 consecutive NHL cases. Considerations included histologic type, clinical manifestation and NHL staging, treatment, response rate and overall survival (OS), event-free survival (EFS), and standardized mortality ratio (SMR).Mucosa-associated lymphoid tissue (MALT) lymphomas constituted the majority (59%) of NHL subtypes, followed by nodal marginal zone lymphomas (NMZLs) (15%) and diffuse large B-cell lymphomas (DLBCLs) (15%). Six lymphoma patients died during the median follow-up of 40.8 months. The corresponding age/sex-adjusted SMR of SS with and without NHLs versus the general population was 3.25 (95% confidence interval [CI] 1.32-6.76) and 1.08 (95% CI, 0.79-1.45), respectively. A "watch and wait" policy was adopted for 9 patients with asymptomatic localized salivary MALT lymphomas. Eight patients with limited-stage MALT lymphomas and extraglandular manifestations were treated with rituximab. Ten MALT lymphoma patients with disseminated disease received chemotherapy with or without rituximab. The 3-year OS and EFS in patients with MALT lymphomas was 97% and 78%, respectively. Rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) was the chosen therapeutic intervention for patients with DLBCLs. A successful outcome was recorded for this group, with 100% OS and EFS at 3 years. Patients with NMZLs had a less favorable outcome, with a 3-year OS of 80% and EFS of 53%. Our results describe the course and prognosis of SS-associated NHL and highlight the need for a risk-stratified treatment approach.


Effects of bromocriptine on periodic limb movements in human narcolepsy.
We studied the effects of bromocriptine on periodic limb movements in sleep (PLMS) of narcoleptic patients. Bromocriptine significantly reduced the number and index of PLMS without improving the nocturnal sleep disruption in that disorder. These results support the hypothesis that dopaminergic mechanisms are involved in the physiopathology of PLMS, and suggest that PLMS do not play a major role in the nocturnal sleep disruption of narcoleptic patients.


Cytoplasmic anion/cation imbalances applied across the membrane capacitance may form a significant component of the resting membrane potential of red blood cells.
Electrical aspects of cell function manifest in many ways. The most widely studied is the cell membrane potential, Vm, but others include the conductance and capacitance of the membrane, the conductance of the enclosed cytoplasm, as well as the charge at the cell surface (an electrical double layer) producing an extracellular electrical potential, the ζ-potential. Empirical relationships have been identified between many of these, but not the mechanisms that link them all. Here we examine relationships between Vm and the electrical conductivities of both the cytoplasm and extracellular media, using data from a suspensions of red blood cells. We have identified linear relationships between extracellular medium conductivity, cytoplasm conductivity and Vm. This is in contrast to the standard model of a resting membrane potential which describes a logarithmic relationship between Vm and the concentration of permeable ions in the extracellular medium. The model here suggests that Vm is partially electrostatic in origin, arising from a charge imbalance at an inner electrical double-layer, acting across the membrane and double-layer capacitances to produce a voltage. This model describes an origin for coupling between Vm and ζ, by which cells can alter their electrostatic relationship with their environment, with implications for modulation of membrane ion transport, adhesion of proteins such as antibodies and wider cell-cell interactions.


Pharmacogenetics and Predictive Testing of Drug Hypersensitivity Reactions.
Adverse drug reactions adverse drug reaction (ADR) occur in approximately 17% of patients. Avoiding ADR is thus mandatory from both an ethical and an economic point of view. Whereas, pharmacogenetics changes of the pharmacokinetics may contribute to the explanation of some type A reactions, strong relationships of genetic markers has also been shown for drug hypersensitivity belonging to type B reactions. We present the classifications of ADR, discuss genetic influences and focus on delayed-onset hypersensitivity reactions, i.e., drug-induced liver injury, drug-induced agranulocytosis, and severe cutaneous ADR. A guidance how to read and interpret the contingency table is provided as well as an algorithm whether and how a test for a pharmacogenetic biomarker should be conducted.


Identification of 14 new alleles at the fucosyltransferase 1, 2, and 3 loci in Styrian blood donors, Austria.
Genes for fucosyltransferases 1 (FUT1:H), 2 (FUT2:Secretor), and 3 (FUT3:Lewis) encode enzymes crucial for ABH and Lewis blood group antigen synthesis. They are highly polymorphic and ethnically and geographically specific. Genetic variations and allele frequencies of FUT1, FUT2, and FUT3 encoding regions and flanking sequences were analyzed in 100 Styrian blood donors by systematic sequencing. Haplotypes were verified with sequence-specific primers. To identify discrepancies, serologically determined ABO and Lewis blood groups were correlated to respective genotypes. Two novel FUT1 alleles were defined by 9C>T (silent) and 991C>A (P331T) mutations, the latter located in the catalytic domain of the enzyme. Five new alleles of FUT2 were found: three were characterized by new variants and two resulted from new combinations of known polymorphisms. The new 412G>A (G138S) mutation also is located in the catalytic domain. A new nonsecretor allele, based on the presence of 428G>A (nonsense), was found. Another FUT2 allele may have resulted from an intragenic crossover event. FUT3 analysis revealed seven novel alleles, partly based on the new mutations 41G>A (R14H), 1060C>G (R354G), 735G>C (silent), and 882C>T (silent). While 41G>A is placed in the cytoplasmic domain and functional, 1060C>G is placed in the catalytic domain. Multiple common and sporadic sequence variations including 14 new alleles at FUT1, FUT2, and FUT3 loci were identified. Four novel mutations result in amino acid substitution in the protein. Three of them are predicted to have adverse effects on the enzyme activity. A novel nonsecretor allele was found.


Effects of perindopril on angiotensin converting enzyme in tissues of the rat.
Perindopril, an orally active angiotensin converting enzyme (ACE) inhibitor, was fed by gavage to male Sprague-Dawley rats. The effect on tissue ACE was measured ex vivo by quantitation of binding of the specific radioligand 125I-3511A to ACE in tissue homogenates. In an acute time-course study perindopril (1, 4 or 8 mg/kg) inhibited plasma ACE activity by more than 90% in 1 h but no inhibition remained after 24 h. Kidney ACE was affected to a similar degree and followed a similar time-course of inhibition to plasma ACE. In contrast, ACE was inhibited to a lesser degree in lung and aorta homogenates, with maximum effect 4-8 h postgavage, and with inhibition persisting 48 h following the dose. In testis homogenates, ACE remained unaltered following the administration of perindopril at all three doses. Therefore we conclude that plasma ACE inhibition does not parallel tissue effects, and that drug penetration into the testis appears to be limited.


Controlling an Outbreak of Multidrug-resistant Acinetobacter baumannii in a Pediatric Intensive Care Unit: a Retrospective Analysis.
Multidrug-resistant Acinetobacter baumannii (MDRAB) is widespread among intensive care units worldwide, posing a threat to patients and the health system. We describe the successful management of a MDRAB outbreak by implementing an infection-control strategy in a pediatric intensive care unit (PICU). This retrospective study investigated the patients admitted to the PICU in periods 1 (8 months) and 2 (7 months), from the index MDRAB case to intervention implementation, and from intervention implementation to cessation of MDRAB spread. An infection-control strategy was designed following six concepts: 1) cohort isolation of colonized patients, 2) enforcement of hand hygiene, 3) universal contact precautions, 4) environmental management, 5) periodic surveillance culture study, and 6) monitoring and feedback. Of the 427 patients, 29 were confirmed to have MDRAB colonization, of which 18 had MDRAB infections. Overall incidence per 1,000 patient days decreased from 7.8 (period 1) to 5.8 (period 2). The MDRAB outbreak was declared terminated after the 6-month follow-up following period 2. MDRAB was detected on the computer keyboard and in condensed water inside the ventilator circuits. The rate of hand hygiene performance was the lowest in the three months before and after index case admission and increased from 84% (period 1) to 95% (period 2). Patients with higher severity, indicated by a higher Pediatric Risk of Mortality III score, were more likely to develop colonization (P = 0.030), because they had invasive devices and required more contact with healthcare workers. MDRAB colonization contributed to an increase in the duration of mechanical ventilation and PICU stay (P < 0.001), but did not affect mortality (P = 0.273). The MDRAB outbreak was successfully terminated by the implementation of a comprehensive infection-control strategy focused on the promotion of hand hygiene, universal contact precautions, and environmental management through multidisciplinary teamwork.


Effect of beta-adrenergic blockade on lipid mobilization induced by fasting in dogs.
To evaluate the contribution of catecholamines to the fasting-induced lipid mobilization prolonged or acute blockade of beta-adrenergic receptors with propranolol was applied in dogs during 72 hrs of food withdrawal. Propranolol given orally in a dose of 15 mg twice daily throughout the whole period of fasting failed to modify the increases in the plasma FFA and glycerol concentrations. The acute beta-adrenergic blockade due to i.v. injection of propranolol (0.5 mg/kg b.w.) caused marked decreases in the plasma glycerol concentration both in the dogs fasting for 24 h and 72 hrs, whereas the effects of propranolol on the plasma FFA concentration was found only in the early stage of fasting. Plasma catecholamine concentrations were enhanced significantly by the 72 hrs food withdrawal and neither prolonged nor acute propranolol administration modified significantly this effect. The fasting-induced decreases in the serum insulin concentration were more pronounced in dogs treated with propranolol. Results of this study indicate that catecholamines are involved in the control of lipolysis during short term starvation. However, under these conditions beta-adrenergic blockade did not impair FFA mobilization most probably due to an enhanced contribution of other hormones to the control of this process.


Efficacy of coenzyme Q10 for improved tolerability of cancer treatments: a systematic review.
The aim of this systematic review was to summarize and evaluate the evidence available for oral supplementation with coenzyme Q10 (CoQ10) to improve the tolerability of cancer treatments. Searches for all published and unpublished controlled trials were carried out on seven databases. Manufacturers of CoQ10 were identified and contacted. Controlled clinical trials of monopreparations of CoQ10 administered orally to cancer patients were included. No language restrictions were imposed. Data were extracted independently by two authors according to predefined criteria. Six studies were included in the review, including three randomized clinical trials and three nonrandomized clinical trials. Patients in five of six studies received anthracyclines. The results suggested that CoQ10 provides some protection against cardiotoxicity or liver toxicity during cancer treatment. However, because of inadequate reporting and analysis, as well as questionable validity of outcome measures, the results are not conclusive. Suggestions that CoQ10 might reduce the toxicity of cancer treatments have not been tested by rigorous trials. Further investigations are necessary to determine whether CoQ10 can improve the tolerability of cancer treatments.


How reliable and valid are the self-reports of sexual behavior among HIV discordant couples in Pune, INDIA.
Reliability of self-reported sexual and safe sex behavior among heterosexual HIV discordant couples was assessed by matching individual responses of couples to a common set of questions and validated by matching with pregnancy and seroconversion during study period. Demographic, clinical and sexual behavior information was collected individually from 457 consenting married discordant couples using structured questionnaires at screening, enrollment and at four quarterly visits. Reliability of self-reports tested using Kappa statistics. At screening, level of agreement about spouse being regular partner (Kappa = 0.96) and having had sexual intercourse with spouse in the last quarter (Kappa = 0.84) was noted. Moderate agreement observed about frequency of condom use (Kappa = 0.639) and condom tear (Kappa = 0.428). Agreement on reporting sexual contacts with spouse and consistent condom use increased (P < 0.001) over follow-ups. Four of 6 couples that seroconverted reported using condoms consistently, and 2 of these seroconverted. Couple histories of all 11 sero-discordant couples reporting pregnancy matched, of these 8 couples reported use of condoms and only 3 couples reported non-use of condoms during the preceding period. Sensitive sexual information can be collected using self-reports but it should be used with caution. Involving couples and using biological parameters concurrently may enhance validity of self-reports.


[Maximal isometric bite force and sports. Preliminary study].
The evaluation of the bite forces coupled with EMG activity of masseter muscles allows to point out temporo-mandibular joint disorders. The intense practice of sports induces stress which may affect the mandibular statics, due to an hyperfunction of the elevator masticatory muscles, especially the masseter muscles. This concept has led us to compare the maximum isometric bite forces of sedentary and physically trained subjects. The aim of this experimentation is to study the maximum isometric bite forces of the premolars, with a force transducer, for two groups of physically trained and sedentary volunteers (25 subjects), with distinction between male and female subjects. Subjects with normal denture and no temporo-mandibular joint disorder were retained. EMG and force recording were synchronized and recorded during 10 seconds of maximal contraction. The male subjects developed a maximal bite-force significantly higher (p < 0.05) compared to the female subjects. There is no significant difference between subjects practising a sport (at least 6 hours a week) and sedentary ones. The evolution of force during the contraction is different between sexes. EMG activity allowed to control that subjects developed a maximal force and an increase in muscular fatigability of physically active females compared to sedentary ones was noticed. The difference of maximal force between men and women is similar to the one found for the locomotor muscles. The analysis of the evolution of the force according to the contraction duration, might be linked to a different distribution of muscular fibers according to the sex. The practice of a sport might increase the fatigability of the masseter muscles and might be a factor inducing a muscular imbalance of the mandibular posture. But the relatively low number of subjects and the absence of well defined distinctions between different kinds of sport limit our conclusions.


Reappraisal of nuclear quadrupole moments of atomic halogens via relativistic coupled cluster linear response theory for the ionization process.
The coupled cluster based linear response theory (CCLRT) with four-component relativistic spinors is employed to compute the electric field gradients (EFG) of (35)Cl, (79)Br, and (127)I nuclei. The EFGs resulting from these calculations are combined with experimental nuclear quadrupole coupling constants (NQCC) to determine the nuclear quadrupole moments (NQM), Q of the halide nuclei. Our estimated NQMs [(35)Cl = -81.12 mb, (79)Br = 307.98 mb, and (127)I = -688.22 mb] agree well with the new atomic values [(35)Cl = -81.1(1.2), (79)Br = 302(5), and (127)I = -680(10) mb] obtained via Fock space multireference coupled cluster method with the Dirac-Coulomb-Breit Hamiltonian. Although our estimated Q((79)Br) value deviates from the accepted reference value of 313(3) mb, it agrees well with the recently recommended value, Q((79)Br) = 308.7(20) mb. Good agreement with current reference data indicates the accuracy of the proposed value for these halogen nuclei and lends credence to the results obtained via CCLRT approach. The electron affinities yielded by this method with no extra cost are also in good agreement with experimental values, which bolster our belief that the NQMs values for halogen nuclei derived here are reliable.


[Studies on neuro-immunologic regulation of senile rats by using the principle of replenishing qi and promoting blood circulation].
To study the mechanism of delaying senility by using the principle of replenishing Qi and promoting blood circulation(RQPBC). The following determinations were carried out in the natural-senile animals which have Qi deficiency and blood stasis Syndrome(24 month old rat) after the treatment. Hemorheological indexes, brain noradrenaline (NE), adrenocorticotropine(ACTH), beta endorphin, cortisol, estradiol, testosterone, interleukin-II (IL-2), tumour necrosis factor (TNF) in the blood, and rat spleen's lymphocyte transformation and induction of IL-2 and the activity of natural killer cells (NKC). The senile rat's above indexes decreased obviously (control: young rats), and by using this principle, all indexes were improved respectively. But these indexes in the young rats cannot be changed by applying this principle. The results indicated that this principle could improve senile body's regulation of neuro-immuno endocrinologic network and keep homeostasis.


Endothelin-1 secretion from cultured rabbit gastric epithelial cells.
It has been shown that endothelin-1 (ET-1) is synthesized in various extraendothelial tissues. Although ET-1 has been reported to have potent ulcerogenic action in the stomach, the synthesis and physiological roles of ET-1 in the gastric mucosa are poorly understood. The aim of the present study was to investigate whether or not cultured gastric epithelial cells secrete ET-1 and possess autocrine functions. Gastric epithelial cells from rabbits were cultured in medium supplemented with 10% FBS after isolation. ET-1 was extracted by C18 columns from serum-free culture media and measured by radioimmunoassay (RIA). Effects of ET-1 on the intracellular concentration of calcium of the cultured cells were examined with Indo-1. Prostaglandin E2 (PGE2) was measured by RIA. Primary cultures of gastric epithelial cells were mainly composed of mucous cells. ET-1 was detected in the culture medium by RIA, and 70 pg/10(6) cells/24 h of ET-1 was secreted by cultured cells. Tumor growth factor-beta (4 ng/ml) and thrombin (8 U/ml) significantly increased ET-1 secretion. Exogenously administered ET-1 up to 10(-6) M neither modulated the intracellular calcium concentration nor affected PGE2 release by these cells. These results suggest that gastric mucous cells in culture secrete ET-1. Further studies are needed to explore the possible involvement of such paracrine function in the reported ulcerogenic action of ET-1.


Changes in plasma, erythrocyte, and urinary magnesium with prolonged swimming exercise.
Erythrocyte, plasma and urinary magnesium were observed in a group of 8 well-trained swimmers and in a group of 10 untrained subjects before, 2 minutes after and 30 minutes after a swimming test. After effort, plasma Mg (pMg) decreased significantly in both groups. Erythrocyte and urinary Mg variations were not significant in this study. PMg decrease after effort was more important in the swimmers group than in the untrained group (12% versus 6% after 2 minutes; 21% versus 4% after 30 minutes). The observed fall in plasma Mg concentration after exercise cannot be explained by a shift into erythrocytes during exercise, since the Mg content of these blood cells did not suffer significant alterations. The possible causes of the observed phenomena are discussed.


CD271 antibody-functionalized microspheres capable of selective recruitment of reparative endogenous stem cells for in situ bone regeneration.
In the strategy of in situ bone regeneration, it used to be difficult to specifically recruit bone marrow mesenchymal stem cells (BM-MSCs) by a single marker. Recently, CD271 has been considered to be one of the most specific markers to isolate BM-MSCs; however, the effectiveness of CD271 antibodies in recruiting BM-MSCs has not been explored yet. In this study, we developed novel CD271 antibody-functionalized chitosan (CS) microspheres with the aid of polydopamine (PDA) coating to recruit endogenous BM-MSCs for in situ bone regeneration. The CS microspheres were sequentially modified with PDA and CD271 antibody through dopamine self-polymerization and bioconjugation, respectively. In vitro studies showed that the CD271 antibody-functionalized microspheres selectively captured significantly more BM-MSCs from a fluorescently labeled heterotypic cell population than non-functionalized controls. In addition, the PDA coating was critical for supporting stable adhesion and proliferation of the captured BM-MSCs. Effective early recruitment of CD271+ stem cells by the functionalized microspheres at bone defect site of SD rat was observed by the CD271/DAPI immunofluorescence staining, which led to significantly enhanced new bone formation in rat femoral condyle defect over long term. Together, findings from this study have demonstrated, for the first time, that the CD271 antibody-functionalized CS microspheres are promising for in situ bone regeneration.


[CEA and CA 19.9: an evaluation by new statistical technics on a group of elderly patients].
New parametric and non parametric statistical methods have been compared in the evaluation of experimental data of CEA and CA 19.9 using a brief program in BASIC. We have found that the distribution of the two markers is the same of that described in literature except for both the means that we have found being slightly higher than that ones described by other authors.


[The role of platelets for the pathophysiology of acute coronary syndromes].
Cardiovascular diseases, especially ischaemic heart disease, are actually the most frequent causes of death in the Western world and represent a central challenge for modern research and medicine. The pathophysiology of ischaemic heart disease is based upon the development and biological remodelling of atherosclerotic plaques. Mainly at late stages, but also in the early phase of atherosclerosis, rupture of the atherosclerotic plaque occurs and may lead to the clinical manifestation of acute coronary syndromes, including unstable angina pectoris, non-transmural or transmural myocardial infarction. Next to inflammation mediating cells like monocytes, platelets play an essential role at early and late stages of atherosclerotic disorders. This review summarizes the basic pathophysiological mechanism of platelet adhesion and secretion, the molecular steps involved in platelet mediated thrombus formation in the atherosclerotic microenvironment and the role of platelet accumulation in reperfused myocardium.


Functional binding interaction identified between the axonal CAM L1 and members of the ERM family.
A yeast two-hybrid library was screened using the cytoplasmic domain of the axonal cell adhesion molecule L1 to identify binding partners that may be involved in the regulation of L1 function. The intracellular domain of L1 bound to ezrin, a member of the ezrin, radixin, and moesin (ERM) family of membrane-cytoskeleton linking proteins, at a site overlapping that for AP2, a clathrin adaptor. Binding of bacterial fusion proteins confirmed this interaction. To determine whether ERM proteins interact with L1 in vivo, extracellular antibodies to L1 were used to force cluster the protein on cultured hippocampal neurons and PC12 cells, which were then immunolabeled for ERM proteins. Confocal analysis revealed a precise pattern of codistribution between ERMs and L1 clusters in axons and PC12 neurites, whereas ERMs in dendrites and spectrin labeling remained evenly distributed. Transfection of hippocampal neurons grown on an L1 substrate with a dominant negative ERM construct resulted in extensive and abnormal elaboration of membrane protrusions and an increase in axon branching, highlighting the importance of the ERM-actin interaction in axon development. Together, our data indicate that L1 binds directly to members of the ERM family and suggest this association may coordinate aspects of axonal morphogenesis.


Theory of planned behavior and college student 24-hour dietary recalls.
Objective: The transition to college is marked by poorer eating behaviors, making emerging adulthood a particularly salient intervention point for improving lifelong health. The present study aims to better understand what psychosocial factors predict eating behaviors of college students using the Theory of Planned Behavior (TPB). Participants & Methods: Dietary recalls were analyzed the Healthy Eating Index (HEI)-2015 scoring system for 67 university students between the ages of 18 and 25 (70.1% female; 49.3% White, 20.9% Black/African American, 13.4% Asian). Results: Haye's PROCESS Model 6 was used. The full model accounted for a significant amount of variance in HEI-2015 scores (F[3, 63] = 3.09, p = .033, R2 = .12). The final model suggested a significant indirect effect of PBC on the relation between ATT and HEI-2015 (β = .859, SE = .637, 95% CI [.009, 2.482]). Conclusions: Although some college students might have favorable attitudes, only those who believe this is within their control actually ate a (somewhat) healthier diet.


Dopamine transporter-mediated conductances increase excitability of midbrain dopamine neurons.
Uptake by Na(+)/Cl(-)-dependent neurotransmitter transporters is the principal mechanism by which extracellular biogenic amine concentrations are regulated. In addition to uptake, the cloned transporter proteins also elicit ion channel-like currents, but the physiological consequences of these currents are unknown. Here, whole-cell patch clamp and perforated-patch recordings show that substrates of the dopamine transporter (DAT), such as dopamine (DA) and amphetamine, increase the firing activity of rat DA neurons in culture. We found that these substrates elicit inward currents that are Na(+)-dependent and blocked by cocaine. These currents are primarily comprised of anions and result in an excitatory response in DA neurons at lower DA concentrations than are required for D2 autoreceptor activation. Thus, in addition to clearing extracellular DA, our results suggest that the currents associated with DAT modulate excitability and may regulate release of neurotransmitter from midbrain DA neurons.


[Cesarean scar pregnancy analysis of 42 cases].
To discuss the diagnosis and treatment strategy of cesarean scar pregnancy (CSP). Forty-two cases of CSP admitted to Peking University First Hospital from Jan. 2003 to Dec. 2008 were analyzed retrospectively, and the clinical characteristics, pelvic Doppler ultrasonography report, management including methotrexate (MTX) therapy, bilateral uterine artery embolism (UAE), curettage and hysterectomy of these 42 women were reviewed. The percentage of human chorionic gonadochopin (hCG) reduction, menstrual period after the treatment of her CSP and recurrent pregnant outcome were also followed. Among the 42 CSP women, 24 (57%) presented with vaginal bleeding, 3 (7%) with lower abdominal pain. The interval between CSP and the last cesarean scar (CS) was 0.5 - 18.0 years and the average duration of gestation was (60 +/- 18) days. Fourteen cases (33%) were finally diagnosed as CSP in our hospital followed by failure of abortion due to misdiagnosed as early uterine pregnancy in other hospitals; one (2%) was finally diagnosed after hysterectomy due to excessive bleeding during curettage because of suspected hydatidiform mole under color sonography; one was diagnosed by MRI after color sonography; the rest 25 women (60%) were all confirmed by color sonography before management. Treatment of these cases included curettage after UAE (17 cases), curettage after UAE and MTX (13 cases), curettage after MTX only (4 cases), MTX only (4 cases) and others (4 cases). No significant difference was found in the average duration of pregnancy, average reduction of serum level of hCG and the operation time for curettage between the first two management group (P > 0.05). All of the 42 cases fully recovered before discharge and the recovery time of menses was averagely (32 +/- 10) days (10 - 60 days) after curettage and 5 reported reduced menstrual blood volume. Three out of the 42 women were pregnant again during follow-up and 1 delivered by CS at 39 weeks of gestation one year after without any complications or CSP. CSP is not common and can be easily misdiagnosed and color ultrasound scan is important in its early diagnosis. UAE combined with MTX followed by curettage is an effective treatment of CSP.


Chemokine Pathways in Cutaneous Melanoma: Their Modulation by Cancer and Exploitation by the Clinician.
The incidence of cutaneous malignant melanoma is rising globally and is projected to continue to rise. Advances in immunotherapy over the last decade have demonstrated that manipulation of the immune cell compartment of tumours is a valuable weapon in the arsenal against cancer; however, limitations to treatment still exist. Cutaneous melanoma lesions feature a dense cell infiltrate, coordinated by chemokines, which control the positioning of all immune cells. Melanomas are able to use chemokine pathways to preferentially recruit cells, which aid their growth, survival, invasion and metastasis, and which enhance their ability to evade anticancer immune responses. Aside from this, chemokine signalling can directly influence angiogenesis, invasion, lymph node, and distal metastases, including epithelial to mesenchymal transition-like processes and transendothelial migration. Understanding the interplay of chemokines, cancer cells, and immune cells may uncover future avenues for melanoma therapy, namely: identifying biomarkers for patient stratification, augmenting the effect of current and emerging therapies, and designing specific treatments to target chemokine pathways, with the aim to reduce melanoma pathogenicity, metastatic potential, and enhance immune cell-mediated cancer killing. The chemokine network may provide selective and specific targets that, if included in current therapeutic regimens, harbour potential to improve outcomes for patients.


Association between GSTP1 CpG methylation and the early phase of lead exposure.
GSTP1 is induced by lead, and thus serves as a biomarker of lead exposure. Lead exposure changes DNA methylation status. We attempted to prove that the methylation of the GSTP1 promoter plays an important role in lead toxicity. We conducted a case-control study of 53 workers from a battery plant and 53 age and sex matched healthy volunteers to determine whether the methylation level of the GSTP1 promoter is associated with the risk of lead poisoning. We employed methylation-specific PCR (MSP) in cell models to determine the relationship between the GSTP1 methylation level and lead exposure. We found no association between GSTP1 methylation and lead exposure. The difference in methylation frequencies between the exposure group and the controls was not statistically significant (p = 0.401), and individuals with the methylated GSTP1 gene was not associated with the risk of lead poisoning (adjusted OR = 1.36, 95% CI, 0.22-8.24). This study suggests that GSTP1 methylation is not involved in the early phase of lead toxicity. Further studies should be performed to detect the association between GSTP1 methylation and the risk of lead poisoning in later phases.


Histometric study of resorption on replanted teeth with enamel matrix-derived protein.
Enamel matrix-derived proteins (Emdogain) stimulate the proliferation of periodontal ligament cells, contributing to their regeneration. This study was to perform histometric assessment of root surface resorption in replanted teeth with the use of Emdogain®. Male Wistar rats (Rattus norvegicus), weighing 180 to 200 gm, were anesthetized, subjected to extraction of the upper right incisor tooth, which was then replanted into the alveoli with the following treatment: (a) control group--tooth with root canal filled with calcium hydroxide paste and (b) treated group--tooth with root canal filled with enamel matrix-derived protein. The animals were sacrificed 25 days after tooth replantation. The maxilla was processed to obtain thin sections (6 µ) and stained with hematoxylin and eosin. The resorption volume percentage of each dental element was calculated from the cementoenamel junction to the apex. Quantification of resorption revealed that Emdogaintreated teeth showed a lower percentage of resorption (31.58%) compared to controls (80.48%) (statistically significant values--t-test p-value=0.0431). It was concluded that Emdogain used as root canal filling has properties capable of showing a lower percentage of resorption in replanted teeth.


Inhibition of nitric oxide synthase and soluble guanylate cyclase induces cardiodepressive effects in normal rat hearts.
Exogenous nitric oxide (NO) has been shown to modulate the contractile force of rat cardiac myocytes. We sought to determine whether endogenous NO-production in the isolated normal rat heart has an effect on myocardial contractility. Hearts of male Wistar rats were investigated using a constant flow perfused non-paced Langendorff preparation. Changes of contractile parameters such as left ventricular peak pressure, dP/dtmax and dP/dtmin, and of coronary perfusion pressure and heart rate were recorded after infusion of the NO-synthase inhibitors N(omega)-nitro-L-arginine (L-NOARG, 0.1 mM, 1.0 mM, n = 6), N(omega)-methyl-L-arginine (L-NMMA, 0.1 mM, 1.0 mM, n = 9) and methylene blue (2 microM, 20 microM, n = 6), the NO-donor sodium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolat (DEA/NO, 0.01 microM, 0.1 microM, n = 12), the specific inhibitor of soluble guanylate cyclase 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 0.1 microM, n = 7) and L-arginine (0.1 mM, 1.0 mM, n = 6). All NO-synthase inhibitors reduced the contractile function of the ventricular muscle before changes in coronary perfusion pressure were evident. The negative inotropic effect of L-NMMA was absent in the presence of an equimolar concentration of L-arginine. ODQ reduced contractile force and coronary perfusion pressure in parallel. By contrast, L-arginine and DEA/NO improved the contractile force of the left ventricle and DEA/NO decreased coronary perfusion pressure. Heart rate was reduced by L-NOARG (1 mM) and methylene blue (20 microM), while DEA/NO (0.1 microM) and L-arginine (1 mM) had a positive chronotropic effect. All these changes were significant (P < 0.05). These results suggest that endogenous NO-production exerts a positive effect on myocardial contraction that is mediated by activation of guanylate cyclase. In addition, NO might be involved in regulation of heart rate.


Novel pattern forming process due to the coupling of convection and phase change.
We present a novel mechanism of pattern formation behind a flat interface during directional solidification of peritectic alloys. It is shown through computational modeling that irregular oscillatory thermosolutal convection can develop in the vertical Bridgman system, even with bottom seeding and bottom cooling. The coupling of the flow oscillation near the interface with solidification leads to ordered layered structures in the solidified crystal, which agree closely with earlier experimental results.


Differential effect of thiol oxidants on the chloroplast H+-ATPase in the light and in the dark.
The effect of thiol oxidants on the light-activated H+-ATPase has been studied in freshly broken and intact chloroplasts. The following observations were made: (i) in chloroplasts which are osmotically shocked after light activation, ferricyanide stimulates the deactivation of the enzyme in the dark, but has little effect in the light; (ii) similarly, o-iodosobenzoate is a most efficient deactivator of the ATPase in intact chloroplasts in the dark but not in the light; (iii) the activated ATPase becomes sensitive to oxidants in the light upon the addition of an uncoupler; (iv) the oxidant-induced deactivation in the dark dominates the stabilizing effect of pyrophosphate or ADP plus Mg2+; (v) full deactivation of the ATPase by dark adaptation or by oxidants does not affect the rate of photophosphorylation under saturating conditions. A model is suggested in which two kinds of conformational changes are involved in the regulation of the ATPase: those induced by the trans-membrane-proton gradient and those by oxidation-reduction of the enzyme. These changes result in the preferential interaction with thiol reductants in the light but with thiol oxidants in the dark.


Role of genetic polymorphism in the SA gene on the blood pressure and prognosis of renal function in patients with immunoglobulin A nephropathy.
The SA gene has been shown to be much more highly expressed in the kidneys of spontaneously hypertensive rats than in the corresponding wild-type strain. Genetic polymorphism of this gene has been shown to play a role in human hypertension, although the details of this association remain controversial. We investigated the possible associations between SA gene polymorphism and both hypertension and the prognosis of renal function in patients with immunoglobulin A nephropathy (IgAN). Genomic DNA was isolated from the peripheral blood of 367 individuals, including 274 patients with histologically proven IgAN and 100 controls without any history of renal disease. The SA genotype was determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) with Pst I. The frequencies of genotypes and alleles were not different between the patients with IgAN and those without renal disease. In the group without renal disease, the SA gene polymorphism was not associated with hypertension. However, in the patients with IgAN the A1 allele frequency was significantly higher in the hypertensives than in the normotensives. The renal survival of the patients with the A2 allele tended to be better than that of those without the A2 allele. The findings thus suggest that SA gene polymorphism may be associated with the renal prognosis of IgAN through its effect on blood pressure. Further, they suggest that the sensitivity to this gene polymorphism increases in patients with renal injury.


Haemodialysis-associated amyloidosis: beta 2-microglobulin alone or associated with globin chains?
1. The protein constituents of amyloid fibrils were characterized in amyloid deposits extracted from surgical material obtained from a 66-year-old patient undergoing maintenance haemodialysis and operated for a carpal tunnel syndrome. 2. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis disclosed the presence of bands at 12 and 14 kDa. Two-dimensional electrophoresis and Western blotting confirmed that the proteins were beta 2-microglobulin (beta 2M) and globin chains. 3. When the effluent of high-performance gel filtration chromatography corresponding to molecular masses of 10-15 kDa was subjected to Edman degradation, only one amino acid residue was found at each step. The 18 residues determined corresponded to the N-terminal sequence of beta 2M. 4. Although globin chains were clearly present in the amyloid material, they were not accessible for sequence determination. The identification of the other protein constituents present in the amyloid material, along with beta 2M, should provide a better understanding of haemodialysis-associated amyloidosis, the mechanisms of formation of which have not yet been completely determined.


Clinically relevant deoxycytidine levels are high enough to profoundly alter 9-beta-D-arabinofuranosylguanine cytotoxicity for human T-cell acute leukemia cells in vitro.
Plasma deoxycytidine levels can vary markedly during chemotherapy, from < 0.05 microM to at least 10.3 microM in T-cell acute lymphoblastic leukemia (T-ALL). This study demonstrates that clinically relevant deoxycytidine levels can dramatically protect human T-ALL cells against 9-beta-D-arabinofuranosylguanine (araG), a promising drug in this leukemia. At 0.4, 1.2, 3.6, and 10.8 microM deoxycytidine, the dose of araG required to kill 50% of MOLT3 T-ALL cells increased 4.23 +/- 1.95-(mean +/- SEM), 23.1 +/- 5.42-, 39.3 +/- 19.3-, and 67.0 +/- 11.5-fold compared to araG without deoxycytidine. Such deoxycytidine concentrations sharply reduced intracellular araG levels and blocked inhibition of DNA synthesis even in the presence of 160 and 640 microM araG. These data offer the first evidence that clinically relevant deoxycytidine levels could profoundly modulate araG toxicity in T-ALL.


Identifying early predictors of mortality in pediatric patients with acute leukemia and pneumonia.
To identify clinical variables of pneumonia in children with acute leukemia that predicted respiratory failure and mortality. A retrospective chart review of children with acute leukemia admitted to the hospital with the diagnosis of pneumonia or ARDS from March 1991 to April 1994. Lucile Salter Packard Children's Hospital at Stanford, a 168-bed teaching hospital and regional tertiary referral center for children in northern California. During this study period, 20% of the 174 admissions of children with acute leukemia had pneumonia at the time of admission or during the course of the hospitalization for a total of 36 admissions. The mean age of these children was 9.2 +/- 1.1 years. Eleven percent of the children with pulmonary infiltrates in one quadrant on the chest x-ray film at the onset of pneumonia and 53% of the children with pulmonary infiltrates in more than one quadrant at the onset of pneumonia died. Fifteen percent of the children without sepsis at the onset of pneumonia and 70% of the children with sepsis at onset died. Eighteen percent of the children without shock at the onset of pneumonia and 75% of the children with shock at the onset died. None of the children died who required < or = 3L/min of O2 to maintain SO2 > or = 95%, but 79% of the children who required > 3L/min O2 died. Using the criteria "> 3 L/min O2 by nasal cannula to maintain SO2 > or = 95%" to identify the nonsurvivors had a sensitivity of 100% and specificity of 88%. This specificity was not increased by combining the criteria "O2 requirements at any time" and "the extent of pulmonary infiltrates at the onset of pneumonia." All children who required mechanical ventilatory support for respiratory failure had previously received > 3 L/min O2 by nasal cannula to maintain SO2 > or = 95% for 37.8 +/- 12.9 h (range 3 to 96 h). Nine of the 10 children in our study who received mechanical ventilation died. In children with acute leukemia and pneumonia, the amount of O2 required to maintain SO2 > or = 95% may identify those who are likely to develop respiratory failure hours before mechanical ventilatory support is needed. The ability to identify children at risk for respiratory failure is not increased by combining the risk factors "oxygen requirements" and "extent of pulmonary infiltrates at the onset of pneumonia". Finally, only 10% of the children who required mechanical ventilatory support survived.


Study on the presence of ochratoxin α in cultures of ochratoxigenic and non- ochratoxigenic strains of Aspergillus carbonarius.
Ochratoxin A (OTA) is a potent nephrotoxin and carcinogen which is found in a wide variety of common foods and beverages and it is produced by several species of Aspergillus and Penicillium. Ochratoxin α (OTα), a major metabolite of OTA, has also been reported to occur in cultures of OTA-producing species. However there is some controversial about the participation of OTα in the biosynthesis of OTA, mainly because its biosynthesis pathway has not yet been completely characterized. Aspergillus carbonarius is the main responsible source of ochratoxin A (OTA) in food commodities such as wine, grapes or dried vine fruits from main viticultural regions worldwide. However, little is known about the presence of OTα in isolates of A. carbonarius. In this study we evaluated the effects of temperature and incubation time on OTα production by both OTA and non-OTA-producing strains of A. carbonarius. OTA and OTα were detected on the basis of HPLC fluorometric response compared with that of their standards and confirmed by HPLC-MS in selected samples. The non-OTA-producing strains did produce neither OTA nor OTα at any of the conditions tested. The OTA-producing strains studied were able to produce both OTA and OTα in most of the conditions tested. In general, higher amounts of OTA than OTα were produced, but a positive correlation in the production of these two metabolites was detected. The lack of production of both OTA and OTα in the non-OTA-producing strains could be caused by the presence of silent genes or by mutations in functional or regulatory genes involved in OTA production.


Antiproliferative and apoptosis-inducing effects of lipophilic vitamins on human melanoma A375 cells in vitro.
The effects of six lipophilic vitamins: tretinoin (ATRA), vitamin D(3) (VD(3)), VE, VK(1), VK(3), and VK(5) on cell proliferation and apoptosis in human A375 melanoma cells were investigated. VD(3), VK(3), and VK(5) were found to inhibit cell proliferation significantly at concentration ranges of 10-100 μmol/L (p<0.01), while the other vitamins did not show inhibitory effects at 100 μmol/L. VK(3) and VK(5) showed the strongest effects with IC(50) values of less than 10 μmol/L. Dacarbazine slightly inhibited the proliferation of A375 cells at a concentration range of 25-100 μmol/L, but the effects were not statistically significant. VK(3) and VK(5) increased annexin-V positive apoptotic cells, as well as activating caspase-3, in A375 cells. Our findings showed that VD(3), VK(3,) and VK(5) inhibited the growth of dacarbazine resistant human melanoma cells, while ATRA, VE, and VK(1) had little effect on the cell growth. The effects of VK(3) and VK(5) were observed at concentrations lower than 10 μmol/L, which are suggested to have resulted from apoptosis-induction in the melanoma cells.


Use of topical petroleum jelly for prevention of sepsis in very low-birthweight infants: a prospective, randomised controlled trial.
Emollient therapy is used frequently to prevent nosocomial infection in the management of preterm infants, despite a lack of adequate evidence of its efficacy. To assess the efficacy of prophylactic whole-body application of pure preservative-free topical petroleum jelly on the incidence of nosocomial sepsis in very low-birthweight (VLBW) infants. A prospective, randomised controlled trial of the application of topical petroleum jelly was conducted. Infants weighing <1250 g at birth and with a gestational age of ≤32 weeks were included. The intervention group received twice-daily topical therapy of 2 g/kg pure, preservative-free topical petroleum jelly until the completion of 34 weeks of gestation. The control group received no topical petroleum jelly treatment. The primary outcome was the incidence of late-onset sepsis during hospitalisation. Other data collected included the pattern of temperature control, weight changes, fluid requirements, serum bilirubin level, electrolyte imbalance and skin condition. Thirty-five infants in the intervention group and 39 in the control group were recruited. Birthweight, gestational age, gender and perinatal variables were comparable in the two groups. There was a trend towards an increased incidence of culture-proven nosocomial sepsis in the intervention group - 19 episodes (54%) in the intervention group vs 16 (41%) in the control group, and an increased rate of NEC - 20% in the intervention group vs 8% in the control group. The intervention group had better skin condition throughout their stay and the incubator ambient temperature was lower in the intervention group in the 1st week of life. The fluid balance of the infants in the intervention group was better, as reflected by their mean (SD) shorter time to regain birthweight [12 (5) vs 14 (6) days], and there were fewer episodes of hypernatraemia in the 1st week of life, although none of these reached statistical significance. However, there was a significantly lower mean (SD) level of maximum hyperbilirubinaemia [157 (40) vs 182 (46) mmol/L, P = 0·02) in the intervention group. Although prophylactic topical application of pure, preservative-free petroleum jelly brought substantial improvement of skin condition and temperature control, it was associated with a trend towards an increased rate of nosocomial sepsis.


The reliability of chest radiographs in predicting left atrial enlargement.
Estimates of left atrial size in patients with suspected cardiac disease play an important role in predicting prognosis and events, as well as treatment decisions. Two methods are commonly used to estimate left atrial size: chest radiography and cardiac ultrasound. This study aims to determine the test characteristics by comparing the use of radiographs to cardiac ultrasound (the gold-standard test). Data from patients older than 18 years admitted to Steve Biko Academic Hospital during 2000-2003 who had both chest radiographs and cardiac ultrasound were included in this cross-sectional, retrospective analysis. Chest radiographs were classified into three quality classes, and the sub-carinal angle (SCA) and sub-angle distance (SAD) were measured twice in all available radiographs by two observers. Intra- and inter-observer variability (three methods) as well as the predictive value of the carinal angle and sub-angle distance measurements were determined using logistic regression (with left atrial enlargement - determined by ultrasound as comparator). Data for 159 patients were available (154 cardiac ultrasounds and 178 chest radiographs). Intra-observer variability for chest radiograph measurements was low with almost perfect concordance (p = 0.000). Inter-observer variability was higher for supine radiographs. Using logistic regression, a linear model was identified which was statistically significant only for erect radiographs. While goodness-of-fit analysis showed that the model fits the data, performance characteristics were poor, with high sensitivity and low specificity, and an area under the ROC curve of 0.62-0.63, depending on type of radiograph and measurement (SCA or SAD). Linearity in the logit of the dependent variable was assessed, and found to be present at the extremes of SCA measurements for the supine radiograph data and in the first three quartiles for erect radiograph data. A nonlinear model determined by fractional polynomial analysis did not perform significantly better than the original linear model. Cut-off values for the SCA of 72° and 84° (erect and supine radiographs, respectively) were found to give the best compromise between sensitivity and specificity. The corresponding cut-off values for SAD were 24.1 and 26.9 mm. Assessment of either SCA or SAD to determine left atrial size was equivalent and repeatable, both with the same observer and between two observers (less so for supine radiographs). While this measure was precise, it was found not to be very accurate. Therefore, chest radiographs are not reliable in predicting left atrial enlargement.


Plant-soil interactions in a changing world.
Evidence is mounting to suggest that the transfer of carbon through roots of plants to the soil plays a primary role in regulating ecosystem responses to climate change and its mitigation. Future research is needed to improve understanding of the mechanisms involved in this phenomenon, its consequences for ecosystem carbon cycling, and the potential to exploit plant root traits and soil microbial processes that favor soil carbon sequestration.


Identification of an N-acetyl keto derivative of fumonisin B1 in corn cultures of Fusarium proliferatum.
A method is presented for the separation and identification of a new N-acetyl keto derivative of fumonisin B1 (FB1) produced in solid corn culture. Cultures of Fusarium proliferatum (M-1597) were purified using preparative hplc, and the new fumonisin was detected by negative-ion esms. Structures were confirmed by 1H- and 13C-nmr spectroscopy. The new fumonisin differs from FB1 in that the tricarballylic acid functionality at the C-15 position of the eicosane backbone is replaced by a ketone and the amino group is acetylated. Direct analysis of the culture material by negative-ion electrospray lc/ms confirmed that the new fumonisin is produced naturally by the fungus.


Specificity of arachidonic acid-induced inhibition of growth and activation of c-jun kinases and p38 mitogen-activated protein kinase in hematopoietic cells.
We demonstrated that arachidonic acid inhibits growth and induces apoptosis in the bcr-abl transformed leukemia cell line, H7.bcr-abl A54 and in human chronic myeloid leukemia hematopoietic cells. This investigation was undertaken to determine the cell-type specificity of this response. We compared the effect of arachidonic acid on H7.bcr-abl A54 cells to Jurkat (human acute T-cell leukemia), U937 (human histiocytic lymphoma) and RPMI 7666 (human normal B-lymphoblasts) cells. Arachidonic acid (100 microM, 72 h) inhibited growth of H7.bcr-abl A54, Jurkat and U937 cells by 82.2, 67.5 and 20%, respectively, but had no effect on RPMI 7666 cells. These effects were investigated in relationship to the activation of p38 mitogen activated protein kinase (p38 MAPK) and c-jun amino-terminal kinase (JNK) by arachidonic acid in these cell lines. Results from these studies suggest that signaling and proliferative responses to arachidonic acid are cell-type specific. Leukemia cells appear to be more sensitive to the antiproliferative effect of arachidonic acid than normal cells.


Halitosis: Current concepts on etiology, diagnosis and management.
Halitosis or oral malodor is an offensive odor originating from the oral cavity, leading to anxiety and psychosocial embarrassment. A patient with halitosis is most likely to contact primary care practitioner for the diagnosis and management. With proper diagnosis, identification of the etiology and timely referrals certain steps are taken to create a successful individualized therapeutic approach for each patient seeking assistance. It is significant to highlight the necessity of an interdisciplinary method for the treatment of halitosis to prevent misdiagnosis or unnecessary treatment. The literature on halitosis, especially with randomized clinical trials, is scarce and additional studies are required. This article succinctly focuses on the development of a systematic flow of events to come to the best management of the halitosis from the primary care practitioner's point of view.


Lack of histological signs in rats dying during the acute phase of experimental auto-immune encephalomyelitis.
Rats dying acutely of experimental auto-immune encephalomyelitis show very meagre histological signs of the disease in routine histology sections. This cannot be explained by postmortal changes. It is suggested that the infiltrating lymphoid cells seen in the central nervous system for surviving rats are involved in the normally occurring self-limitation of the disease.


Adjuvant immunotherapy of N-[4(5-nitro-2-furyl)-2-thiazolyl]-formamide-induced bladder tumors.
The prophylactic effect of maltose tetrapalmitate (MTP), a newly developed non specific immunoadjuvant in preventing or delaying bladder cancer induction by N-[4(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) or in reducing the growth rate of the induced tumor was compared to other well-known immunoadjuvants (BCG, C. parvum, levamisole and pyran copolymer). The evaluation of the prophylactic role of immunoadjuvants demonstrated that MTP, levamisole and C. parvum were the most effective in prolonging animal survival. MTP was found superior to either of them in reducing the tumor size. The development of lung metastasis was lower in the group receiving MTP or C. parvum. Next, MTP was studied for its therapeutic effect against primary FANFT induced tumor. The subcutaneous (s.c.) and oral routes of MTP administration and their combination with intravesical route were tried. Combinations of intravesical with s.c. or oral MTP were most effective in reducing tumor size, obtaining lower metastases along with greater mononuclear lymphocyte infiltration in the primary tumor.


An ATP-grasp ligase involved in the last biosynthetic step of the iminomycosporine shinorine in Nostoc punctiforme ATCC 29133.
We investigated the genetic basis for mycosporine sunscreen biosynthesis by the cyanobacterium Nostoc punctiforme ATCC 29133. Heterologous expression in Escherichia coli of three contiguous N. punctiforme genes (NpR5600, NpR5599, and NpR5598, here named mysA, mysB, and mysC, respectively) led to the production of mycosporine-glycine, an oxomycosporine. Additional expression of gene NpF5597 (mysD) led to the conversion of mycosporine-glycine into iminomycosporines (preferentially shinorine but also others like mycosporine-2-glycine and porphyra-334). This represents a new mode of enzymatic synthesis for iminomycosporines, one that differs in genetic origin, mechanism, and apparent substrate specificity from that known in Anabaena variabilis ATCC 29413. These results add to the emerging profile of the protein family of ATP-dependent ligases, to which the mysC product belongs, as important condensation enzymes in microbial secondary metabolism.


Changes of Supraspinatus Muscle Volume and Fat Fraction After Successful or Failed Arthroscopic Rotator Cuff Repair.
Muscle atrophy and fatty infiltration are limiting factors for successful rotator cuff (RC) repair. Quantitative data regarding these hallmarks of degenerative muscle changes after RC repair in humans are scarce. By utilizing a new application of the 6-point Dixon magnetic resonance imaging technology, 3-dimensional volume and fat fraction analysis of the whole RC muscle have become possible. Quantitative analysis of atrophy and fatty infiltration of the supraspinatus muscle after healed and failed RC tendon-to-bone repair. Cohort study; Level of evidence, 3. Muscle volume and fat fraction were measured preoperatively and at 3 and 12 months postoperatively in 19 failed and 21 healed arthroscopic supraspinatus tendon repairs, with full muscle volume segmentation and magnetic resonance Dixon sequences. In both groups, the muscle volume initially decreased 3 months after RC repair by -3% in intact (P = .140) and -10% in failed repair (P = .004) but recovered between 3 and 12 months to 103% (P = .274) in intact and 92% (P = .040) in failed repairs when compared with the preoperative volume (difference of change between groups, preoperative to 12 month: P = .013). The supraspinatus muscle's fat fraction did not significantly change after successful repair (6.5% preoperative, 6.6% after 3 months, and 6.7% after 12 months; all nonsignificant). There was, however, a significant increase from 7.8% to 10.8% at 3 months (P = .014) and 11.4% at 12 months (P = .020) after failed repair (difference between groups at 3- and 12-month follow-up: P = .018 and P = .001, respectively). After successful arthroscopic repair, RC tendon tear-induced fatty infiltration can be almost stopped, and muscle atrophy can even be slightly reversed. In case of a failed repair, however, these changes are further pronounced during the first 3 postoperative months but seem to stabilize thereafter.


Catalytic triad heterogeneity in S51 peptidase family: Structural basis for functional variability.
Peptidase E (PepE) is a nonclassical serine peptidase with a Ser-His-Glu catalytic triad. It is specific for dipeptides with an N-terminal aspartate residue (Asp-X dipeptidase activity). Its homolog from Listeria monocytogenes (PepElm) has a Ser-His-Asn "catalytic triad." Based on sequence alignment we predicted that the PepE homolog from Deinococcus radiodurans (PepEdr) would have a Ser-His-Asp "catalytic triad." We confirmed this by solving the crystal structure of PepEdr to 2.7 Å resolution. We show that PepElm and PepEdr lack the Asp-X dipeptidase activity. Our analyses suggest that absence of P1 pocket in the active site could be the main reason for this lack of typical activity. Sequence and structural data reveal that the PepE homologs can be divided into long and short PepEs based on presence or absence of a C-terminal tail which adopts a β-hairpin conformation in the canonical PepE from Salmonella enterica. A long PepE from Bacillus subtilis with Ser-His-Asp catalytic triad exhibits Asp-X dipeptidase activity. Whereas the three long PepEs enzymatically characterized till date have been found to possess the Asp-X dipeptidase activity, the three enzymatically characterized short PepEs lack this activity irrespective of the nature of their catalytic triads. This study illuminates the structural and functional heterogeneity in the S51 family and also provides structural basis for the functional variability among PepE homologs.


Real-Time Quantification of Cartilage Degeneration by GAG-Targeted Cationic Nanoparticles for Efficient Therapeutic Monitoring in Living Mice.
One of the characterizations of degenerative cartilage disease is the progressive loss of glycosaminoglycans (GAGs). The real-time imaging method to quantify GAGs is of great significance for the biochemical analysis of cartilage and diagnosis and therapeutic monitoring of cartilage degeneration in vivo. To this end, a cationic photoacoustic (PA) contrast agent, poly-l-lysine melanin nanoparticles (PLL-MNPs), specifically targeting anionic GAGs was developed in this study to investigate whether it can image cartilage degeneration. PLL-MNP assessed GAG depletion by Chondroitinase ABC in vitro rat cartilage and intact ex vivo mouse knee joint. A papain-induced cartilage degenerative mice model was used for in vivo photoacoustic imaging (PAI). Oral cartilage supplement glucosamine sulfate was intragastrically administered for mice cartilage repair and the therapeutic efficacy was monitored by PLL-MNP-enhanced PAI. Histologic findings were used to further confirm PAI results. In vitro results revealed that the PLL-MNPs not only had a high binding ability with GAGs but also sensitively monitored GAG content changes by PAI. The PA signal was gradually weakened along with the depletion of GAGs in cartilage. Particularly, PLL-MNPs depicted the cartilage structure and the distribution of GAGs was demonstrated in PA images in ex vivo joints. Compared with the normal joint, a lower signal intensity was detected from degenerative joint at 3 weeks after papain injection, suggesting an early diagnosis of cartilage lesion by PLL-MNPs. Importantly, this PA-enhanced nanoprobe was suitable for monitoring in vivo efficacy of glucosamine sulfate, which effectively blocked cartilage degradation in a high dose manner. In vivo imaging findings correlated well with histological examinations. PLL-MNPs provided sensitive visualization of cartilage degeneration and promising monitoring of therapeutic response in living subjects.


Adenovirus-based vaccines-a platform for pandemic preparedness against emerging viral pathogens.
Zoonotic viruses continually pose a pandemic threat. Infection of humans with viruses for which we typically have little or no prior immunity can result in epidemics with high morbidity and mortality. These epidemics can have public health and economic impact and can exacerbate civil unrest or political instability. Changes in human behavior in the past few decades-increased global travel, farming intensification, the exotic animal trade, and the impact of global warming on animal migratory patterns, habitats, and ecosystems-contribute to the increased frequency of cross-species transmission events. Investing in the pre-clinical advancement of vaccine candidates against diverse emerging viral threats is crucial for pandemic preparedness. Replication-defective adenoviral (Ad) vectors have demonstrated their utility as an outbreak-responsive vaccine platform during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Ad vectors are easy to engineer; are amenable to rapid, inexpensive manufacturing; are relatively safe and immunogenic in humans; and, importantly, do not require specialized cold-chain storage, making them an ideal platform for equitable global distribution or stockpiling. In this review, we discuss the progress in applying Ad-based vaccines against emerging viruses and summarize their global safety profile, as reflected by their widespread geographic use during the SARS-CoV-2 pandemic.


Identification of passive elastic joint moments in the lower extremities.
Musculotendon actuators produce active and passive moments at the joints they span. Due to the existence of bi-articular muscles, the passive elastic joint moments are influenced by the angular positions of adjacent joints. To obtain quantitative information about this passive elastic coupling between lower limb joints, we examined the passive elastic joint properties of the hip, knee, and ankle joint of ten healthy subjects. Passive elastic joint moments were found to considerably depend on the adjacent joint angles. We present a simple mathematical model that describes these properties on the basis of a double-exponential expression. The model can be implemented in biomechanical models of the lower extremities, which are generally used for the simulation of multi-joint movements such as standing-up, walking, running, or jumping.


Role of the Transcriptional Regulator ArgR in the Connection between Arginine Metabolism and c-di-GMP Signaling in Pseudomonas putida.
The second messenger cyclic di-GMP (c-di-GMP) is a key molecule that controls different physiological and behavioral processes in many bacteria, including motile-to-sessile lifestyle transitions. Although the external stimuli that modulate cellular c-di-GMP contents are not fully characterized, there is growing evidence that certain amino acids act as environmental cues for c-di-GMP turnover. In the plant-beneficial bacterium Pseudomonas putida KT2440, both arginine biosynthesis and uptake influence second messenger contents and the associated phenotypes. To further understand this connection, we have analyzed the role of ArgR, which in different bacteria is the master transcriptional regulator of arginine metabolism but had not been characterized in P. putida. The results show that ArgR controls arginine biosynthesis and transport, and an argR-null mutant grows poorly with arginine as the sole carbon or nitrogen source and also displays increased biofilm formation and reduced surface motility. Modulation of c-di-GMP levels by exogenous arginine requires ArgR. The expression of certain biofilm matrix components, namely, the adhesin LapF and the exopolysaccharide Pea, as well as the diguanylate cyclase CfcR is influenced by ArgR, likely through the alternative sigma factor RpoS. Our data indicate the existence of a regulatory feedback loop between ArgR and c-di-GMP mediated by FleQ. IMPORTANCE Identifying the molecular mechanisms by which metabolic and environmental signals influence the turnover of the second messenger c-di-GMP is key to understanding the regulation of bacterial lifestyles. The results presented here point at the transcriptional regulator ArgR as a central node linking arginine metabolism and c-di-GMP signaling and indicate the existence of a complex balancing mechanism that connects cellular arginine contents and second messenger levels, ultimately controlling the lifestyles of Pseudomonas putida.


Contrasting mechanisms of secondary metabolite accumulation during leaf development in two tropical tree species with different leaf expansion strategies.
Young leaves of most species experience remarkably higher herbivore attack rates than mature leaves. Considerable theoretical effort has focused on predicting optimal defense and tradeoffs in defense allocation during leaf expansion. Among others, allocation to secondary chemistry may be dependent on growth constraints. We studied flavanoid production during leaf development in two species of Inga (Fabaceae: Mimosoideae) with different expansion strategies: Inga goldmanii, a species with slowly expanding young leaves, and Inga umbellifera, a species with fast-expanding young leaves. In these two species, the most abundant and toxic class of defensive compounds is flavanoids (which include tannins). We measured their concentration by leaf dry weight, their total content per leaf, their HPLC chemical profile and their toxicity to a generalist herbivore at different expansion levels. Although in both species the flavanoid concentration decreased with increasing leaf expansion, that decrease was twice as pronounced for I. umbellifera as it was for I. goldmanii. I. umbellifera leaves produced flavanoids only during the first half of their development while I. goldmanii leaves continued production throughout. The changes in flavanoid HPLC profiles and toxicity were also more dramatic for I. umbellifera, which had different flavanoids in young than in mature leaves. Relative to I. umbellifera, I. goldmanii showed smaller changes in both flavanoid composition and toxicity in the transition from young to mature leaves. These results indicate that, even though young leaves suffer higher rates of attack and are predicted to have better chemical defenses than mature leaves, growth constraints may modulate defense allocation and thus, evolution of defense strategies.


[Responses of moss biocrusts respiration to simulated grazing and trampling disturbance with different intensities on the fenced forestland of Loess Plateau, China].
The changes in soil properties caused by grazing and trampling are important reasons for the changes in soil respiration rates, carbon fixation, and emission. However, the effects of different intensities of grazing and trampling on biocrusts respiration rate are unclear. In this study, we simulated grazing and trampling disturbances of 10%, 30%, 50%, and 70% intensity on moss biocrusts developed in aeolian sandy soil on Loess Plateau, with undisturbed moss biocrusts serving as a control. The changes in respiration rate of moss biocrusts were monitored continuously, and its responses to different disturbance intensities were analyzed. The results showed that: 1) moderate disturbance stimulated moss biocrusts respiration, while heavy disturbance inhibited that. The respiration rate of moss biocrusts was increased by 41.1% and 22.2% at disturbance intensities of 10% and 30%, but was decreased by 8.9% and 15.3% at disturbance intensities of 50% and 70%, respectively. 2) The trampling disturbance significantly changed soil temperature but did not affect soil water content. In comparison to the control, soil temperature of biocrusts was decreased by 0.4 and 1.2 ℃ at disturbance intensities of 10% and 30%, but it was increased by 1.1 and 1.0 ℃ at disturbance intensities of 50% and 70%, respectively. 3) The respiration rate of moss biocrusts showed a significant exponential relationship with soil temperature and a linear positive relationship with soil water content under different disturbance intensities. However, the correlation between respiration rate of moss biocrust and the characteristics of moss biocrust was not significant. Soil temperature and water content could explain 70.6%-96.3% and 49.1%-70.0% of the total variation of respiration rate of moss biocrusts, respectively. In conclusion, grazing and trampling affected the respiration rate of moss biocrusts, with short-term moderate grazing and trampling would have positive effects. On the other hand, excessive grazing and trampling would reduce the rate of moss biocrust respiration. As a result, future studies on soil carbon balance of the Loess Plateau should consider the effects of grazing and trampling on biocrust respiration.


Relationship between dietary intake and use of protease inhibitors with anthropometric and biochemical parameters of lipodystrophy in people living with hiv.
The lipodystrophy syndrome is characterized by redistribution of body fat and disorders of glicidic and lipid metabolism. Although its etiology is related to infection and drug therapy, there is little evidence regarding the nutritional disturbances on this association. This study aimed to assess the relationship between dietary intake and use of protease inhibitors (PIs) with anthropometric and biochemical parameters in HIV positive patients. The study included 50 patients. A questionnaire about socioeconomic status, lifestyle and infection history was taken. In addition, it was conducted the evaluation of dietary intake (frequency questionnaire), anthropometric parameters (body mass index, waist circumference, triceps skinfold, corrected arm muscle area) and biochemistry tests (glycemia and lipid profile). Only 37% of the sample was classified as "good food consumption", 54% were overweight or obese and 66% presented high waist circumference. The group with good food consumption had higher HDL-C (p=0.04) levels than the group with poor food consumption. Patients taking PIs presented VLDL-C (p=0.023) and triglycerides (p=0.024) levels significantly higher. These results indicated the necessity for continuous monitoring of HIV-positive patients and non-pharmacological interventions such as nutrition education and practice of physical exercises.


Massive lower gastrointestinal bleeding due to 'Dieulafoy's vascular malformation' of the jejunum: case report.
Dieulafoy reported three cases of massive gastric hemorrhage due to a dilated submucosal artery in 1898, and since then, more than 100 cases of this gastric vascular malformation have been reported in the literature. These same pathologic lesions are even a rarer occurrence in the small bowel. This article reports a 38-year-old hypotensive male who presented to the hospital after an acute onset of massive lower gastrointestinal hemorrhage; superior mesenteric angiography demonstrated an actively bleeding lesion in a proximal jejunal branch. Intraoperative small bowel endoscopy via an enterotomy demonstrated a 4 mm bleeding submucosal lesion 30 cm distal to the ligament of Treitz. A literature review revealed six other cases of Dieulafoy's vascular malformation that occurred in the small bowel, with the lesions located in the proximal jejunum between 15 cm and 45 cm distal to the ligament of Treitz. The cause of these lesions is unknown. This case demonstrates the importance of preoperative angiography and intraoperative endoscopy when massive lower gastrointestinal hemorrhage is suspected to be from a small bowel source.