Within-individual differences in plasma ferritin, retinol-binding protein, and zinc concentrations in relation to inflammation observed during a short-term longitudinal study are similar to between-individual differences observed cross-sectionally.
Cross-sectional (CS) surveys indicate that individuals with acute inflammation have higher plasma ferritin (pF), and lower retinol-binding protein (RBP) and zinc (pZn) concentrations than those without. In populations with a high burden of infection, correction factors (CFs) or regression corrections (RCs) are applied to biomarkers to estimate the prevalence of micronutrient (MN) deficiencies adjusted for inflammation. This assumes that individuals with and without inflammation have the same nutritional status, which may not be the case. The aim of this study was to investigate relations between short-term, longitudinal within-individual changes in acute phase proteins (C-reactive protein [CRP], α-1-acid glycoprotein [AGP]) and biomarkers of MN status (pF, soluble transferrin receptor [sTfR], RBP, and pZn), and compare them to CS differences. Two blood samples were obtained 21 d apart from 451 asymptomatic Burkinabé children aged 6-23 mo. To calculate CFs, inflammation was defined as CRP >5 mg/L or AGP >1 g/L, or both. The RC approach adjusted MN biomarkers to a presumably healthy reference point within the study population (10th percentile CRP or AGP concentration). CS CFs and RCs were estimated from a naive regression model, treating observations from the same children as independent. Longitudinal CFs and RCs, to estimate effects of within-individual changes in CRP and/or AGP, were estimated from general linear models, accounting for repeated measures. In CS models, geometric mean pF and sTfR concentrations were 8-340% greater, and RBP and pZn 2-18% lower, in children with inflammation than those without. Except for sTfR, biomarker concentrations differed in the same direction and by similar magnitude within individuals whose inflammation status changed during the observation period. Although geometric mean MN concentrations differed significantly when adjusted with CS compared with longitudinal models, the estimated prevalence of MN deficiencies in CS and longitudinally adjusted models was similar. The CF and RC approaches to adjust MN biomarkers for inflammation between individuals in CS surveys are valid approaches for data collection and programmatic decisions in comparable populations. This study was registered at clinicaltrials.gov as NCT00944853.


[Secondary osteoporosis UPDATE. Bone metabolic change and osteoporosis during pregnancy and lactation].
Calcium transfer from the mother to the infant during pregnancy and lactation plays an extremely important role in the bone health of the mother and neonate. Calcium aids in bone health through all ages but is especially crucial during pregnancy and lactation. Changes in the structure and metabolism of bone during pregnancy and the early stage of postpartum are evaluated by investigating bone mineral density (BMD), bone histomorphometry and bone markers of human or animal models. The bone resorption increased at the end of pregnancy and lactation, and the bone formation increases and the bone structure is almost recovered after cessation of lactating in postpartum. Puerperal BMD remained static over the subsequent 5-10 years. If the women have a low BMD at this stage of their reproductive life, it tends not to improve over this time. Perhaps identification of this at-risk group may lead to effective interventions to reduce fracture risk in later life.


Immunohistochemical and ultrastructural localization of leptin and leptin receptor in human white adipose tissue and differentiating human adipose cells in primary culture.
Leptin is mainly produced in white adipose tissue and acts both at distant sites and locally at the tissue from which it originates. The cellular and subcellular localization of leptin and its receptor (Ob-receptor [Ob-R]) and their relationship to various stages of fat cell maturation have not been characterized as yet. Therefore, we analyzed leptin and Ob-R by using reverse transcriptase-polymerase chain reaction, immunohistochemistry, and ultrastructural immunogold labeling in human white adipose tissue and in human adipocyte cell cultures at early and late stages of differentiation. Both leptin and its receptor were present in mature unilocular fat cells. The thin cytoplasmic rim of the adipocytes exhibited the strongest expression of both leptin and Ob-R. At early stages of differentiating human adipocytes, leptin was mainly expressed in multilocular preadipocytes, whereas the Ob-R was found predominantly on fibroblast-like cells. Other cellular components of human white adipose tissue were characterized by anti-CD31 for endothelial cells, anti-CD68 for macrophages, and antibodies specifically labeling B-cells and T-cells. In addition to fat cells, endothelial cells were immunopositive for the full-length leptin receptor. On the ultrastructural level, leptin was mainly found attached to cellular membranes and in small alveolate vesicle-like structures in the cytoplasm of adipocytes. Leptin was also present on the cell membranes of endothelial cells and macrophages. We conclude that the expression of the Ob-R in human white adipose tissue is not restricted to adipocytes but is present in resident endothelial and immune cells. Ultrastructural localization studies revealed an association of leptin with cell membranes and small vesicles. The cellular and subcellular distribution of leptin and its receptor suggests an important autocrine and paracrine role for leptin in human adipose tissue.


Unusual formation of a [NiSFe(2)(CO)(6)] cluster: a structural model for the inactive form of [NiFe] hydrogenase.
The synthesis and characterisation of the trinuclear Ni-Fe complex [Ni(L(2))SFe(2)(CO)(6)] (1) formed from the reaction of [Ni(L(1))] with Fe(3)(CO)(12) is described. The single-crystal X-ray structure of 1 shows Ni(ii) bound to three thioether R(2)-S donors and bridged by a sulfide (S(2-)) group to two Fe(CO)(3) units. undergoes a reversible one-electron reduction process at E(1/2) = -1.62 V vs. Fc(+)/Fc to generate 1 (-), which has been characterised by UV-vis and IR spectroelectrochemistry and by EPR spectroscopy. DFT calculations on 1and 1 (-) reveal electronic structures that are delocalised across the NiFe(2) core. The SOMO in 1 (-) possesses Ni-Fe and Fe-Fe anti-bonding character and lies approximately in the plane defined by the equilateral triangle of Ni and Fe atoms. It possesses d-orbital contributions of 18.5, 15.0 and 19.8% for the Ni(1), Fe(1) and Fe(2) atoms, respectively. The Ni-S(sulfide) bond length in 1 [2.1654(7) A] is identical to that for the bridging sulfide found in the oxidised inactive form of the [NiFe] hydrogenase from D. vulgaris (2.16 A). Thus, 1 provides a useful comparison for biological [NiFe] centres bridged by sulfide donors.


Perioperative Mortality Following Oesophagectomy and Pancreaticoduodenectomy in Australia.
Oesophagectomy (OG) and pancreaticoduodenectomy (PD) remain associated with significant perioperative mortality rates (POMR). Improved outcomes in high-volume centres have led to these procedures being centralised in some countries. This retrospective, population-based cohort study was conducted to determine the Australian national, and state and territory based POMR associated with OG and PD, and assess trends over time. Logistic regression analysis was performed using de-identified procedural data between 1 July 2005 and 30 June 2013 from the Australian Institute of Health and Welfare. Codes relating to OG and PD contained in the Australian Classification of Health Interventions were used to extract patient data. Mortality rates were risk adjusted for age, gender and urgency of admission. Temporal trends and differences between states/territories were investigated. The average Australian POMR throughout the study period was 3.5 and 3.0% for OG and PD, respectively. OG POMR showed no significant change over time (P = 0.30) or variation between states (P = 0.079). The annual POMR associated with PD, however, showed a significant decrease during the study period (P = 0.01) with variation in PD POMR outcomes evident amongst different regions (P = 0.0004). This study demonstrates a comparable Australian PD and OG POMR when correlated with international studies. National PD POMR improved throughout the study with consistent improvement across the states and territories. This study does, however, show variation in PD POMR between states and territories. Potential intra-state variation merits further investigation.


Synthesis, growth, thermal and optical studies on third order nonlinear optical material (E)-2-{3-[2-(4-chlorophenyl) vinyl]-5,5-dimethylcyclo-hex-2-en-1-ylidene}malononitrile for optoelectronic application.
A new polyene like organic molecule (E)-2-{3-[2-(4-chlorophenyl) vinyl]-5,5-dimethylcyclo-hex-2-en-1-ylidene}malononitrile (Cl1) was synthesized by knoevenagel condensation method. The Cl1 Single crystals were successfully grown by the slow evaporation method at a constant temperature 35°C. Single crystal XRD confirms the Cl1 molecule belongs to monoclinic crystal system and space group P21/C with a=10.114, b=11.127, c=14.929 and V=1668.9 and Z=4. The grown Cl1 crystals were subjected to FTIR and 13C NMR studies to confirm the synthesized compound. The linear optical property of Cl1 crystal has been studied using UV-Vis-NIR spectroscopy in the wavelength range 190 nm-1100 nm. The thermal properties of Cl1 crystal were studied by using TG and DTA analysis. The refractive index of Cl1 crystal has measured using Abbe's refractometer and found to be 1.648. The third order nonlinear optical property of Cl1 crystal has been investigated using Z-scan technique with HeNe laser. Photoluminescence (PL) spectrum of Cl1 crystal was carried out using xenon lamp, which shows high intense emission peak at wavelength 614 nm. Laser optical damage threshold (LDT) of Cl1 crystal has studied using Nd-YAG laser (10 Hz, 420 mJ, 1064 nm).


Synthesis and DNA interaction of a mixed proflavine-phenanthroline Tröger base.
We report the synthesis of an asymmetric Tröger base containing the two well characterised DNA binding chromophores, proflavine and phenanthroline. The mode of interaction of the hybrid molecule was investigated by circular and linear dichroism experiments and a biochemical assay using DNA topoisomerase I. The data are compatible with a model in which the proflavine moiety intercalates between DNA base pairs and the phenanthroline ring occupies the DNA groove. DNase I cleavage experiments were carried out to investigate the sequence preference of the hybrid ligand and a well resolved footprint was detected at a site encompassing two adjacent 5'-GTC.5-GAC triplets. The sequence preference of the asymmetric molecule is compared to that of the symmetric analogues.


Paeonol inhibits anaphylactic reaction by regulating histamine and TNF-alpha.
Paeonol, a major phenolic component of Moutan Cortex, was known to have antiaggregatory, antioxidant and antiinflammatory activities. In the present study, we tried to elucidate the effects of paeonol on anaphylactic reaction and its mode of action. Paeonol significantly inhibited histamine release from the rat peritoneal mast cells (RPMCs) treated with compound 48/80, a mast cell degranulator. The release of tumor necrosis factor (TNF)-alpha mast cell activating cytokine was significantly suppressed in RBL-2H3 mast cells pretreated with anti-dinitrophenyl (DNP) immunoglobulin E (IgE) in a dose-dependent manner. Paeonol significantly inhibited IgE production in B cells activated by anti-CD40 mAb, recombinant interleukin-4 (rIL-4) and recombinant histamine releasing factor (rHRF). Paeonol effectively downregulated the expression of IL-4 in the activated B cells by reverse transcription-polymerase chain reaction (RT-PCR). We also confirmed that paeonol effectively inhibited anaphylactic shock in mice by 90% at a dose of 0.5 mg/mouse versus PBS treated control 2 h after the i.p. injection of compound 48/80. These results suggest that paeonol has antianaphylatic activity by regulating histamine and TNF-alpha.


Evaluation of a Traumatic Vertebral Artery Occlusion.
Penetrating neck injury occurs in 5%-10% of all trauma cases and carries a significant burden of morbidity and mortality (15%). We describe the evaluation and management of a 25-year-old man shot in the neck with occlusion of the left vertebral artery from its origin to C6. This is a case report in which medical data were analyzed retrospectively with institutional review board approval. Neurologic examination revealed paresthesias and dysesthesias in a left C8 dermatomal distribution. Computed tomography angiography of the neck demonstrated no opacification of the left vertebral artery from its origin to C6. Magnetic resonance imaging of the cervical spine revealed an acute infarct in the left cerebellum. A cerebral angiogram highlighted hemodynamic compromise, and the patient was felt to be at significant risk of further cerebral infarction. Augmenting flow to the posterior circulation would mitigate that risk. The patient was taken to the operating room for a transposition of the vertebral artery to the common carotid artery. The patient presented with silent cerebellar infarction due to a vertebral artery injury and impending vertebrobasilar insufficiency. This case demonstrates clinical evaluation of the posterior circulation and treatment with a bypass technique through mobilization of the vertebral artery from the boney vertebral foramen with anastomosis to the common carotid.


Methotrexate polyglutamation in relation to infliximab pharmacokinetics in rheumatoid arthritis.
The combination of methotrexate (MTX) with infliximab can modify infliximab pharmacokinetics and lower the incidence of antibodies against infliximab (ATIs). We hypothesised that the pharmacokinetic interaction between MTX and infliximab is related to activation of MTX to immunosuppressive MTX polyglutamates (MTXPGs). Adult patients with rheumatoid arthritis receiving weekly MTX with infliximab for more than 3 months were enrolled in a cross-sectional study. Blood was collected at trough before the infusion of infliximab. Red blood cell (RBC) MTXPGs were measured using liquid chromatography, and circulating levels of infliximab were measured using a cell-based assay. ATIs were measured using enzyme immunoassays. Statistical analyses consisted of multiple regression and Wilcoxon tests. In the 61 patients enrolled in the study, ATIs were detected in 11 (18%). Regression analyses revealed that lower infliximab levels (median 3.3 µg/ml) were associated with the presence of ATIs and lower RBC MTXPG levels (median 28 nmol/l) (p<0.05). Logistic regression revealed that RBC MTXPG levels above 25 nmol/l were associated with a 4.7-fold lower likelihood of having ATIs (OR=4.7; 95% CI 1.1 to 20.8; p=0.02). None of the 12 patients with RBC MTXPG levels above 50 nmol/l tested positive for ATIs. These hypothesis-generating data indicate that MTXPGs are associated with infliximab pharmacokinetics and ATI formation.


The influence of patient characteristics on the appropriateness of surgical treatment for breast cancer patients. Progetto Oncologia Femminile.
Within the framework of a multi-annual educational intervention sponsored by the Ministry of Health and regional health authorities, patterns of the care delivered to breast cancer patients in Italian general hospitals were monitored in order to identify areas of practice whose quality was in need of improvement. Information on the diagnostic and therapeutic procedures in 63 general hospitals in eight Italian regions performed in 1724 consecutive breast cancer patients were retrospectively gathered from medical records. Quality of care was assessed by a diagnostic and therapeutic score based on the observed degree of compliance with previously established courses of action. The median value of the overall diagnostic and staging score was 60%. About one-third of surgical operations (38%) were inappropriate: one-fourth (24%) of patients with stage I-II disease had unnecessarily radical surgery (i.e., Halsted mastectomy), and limited surgery in patients with small tumors (i.e., < or = 2 cm) was under utilized. Chronological age influenced physicians' behaviour: elderly patients were more likely to have a less intensive diagnostic work-up and less appropriate surgical treatment (with more frequent performance of an unnecessary radical operation and a less frequent utilization of limited surgery), independently of their overall health status. The presence of one or more co-existent diseases was associated with a failure to undergo axillary clearance and with a lower utilization of conservative surgery independently of age. In accord with others, this study confirms the existence of a clinically important effect of patient age on diagnostic and therapeutic behaviour and the use of unnecessarily radical surgery procedures. The paper discusses the implications of these findings for the next stage of the educational project, in which practice guidelines will be developed and implemented to improve the quality of care for breast cancer patients.


Open reading frames encoding a protein kinase, homolog of glycoprotein gX of pseudorabies virus, and a novel glycoprotein map within the unique short segment of equine herpesvirus type 1.
DNA sequence analysis of the unique short (Us) segment of the genome of equine herpesvirus type 1 Kentucky A strain (EHV-1) by our laboratory and strains Kentucky D and AB1 by other workers identifies a total of nine open reading frames (ORF). In this report, we present the DNA sequence of three of these newly identified ORFs, designated EUS 2, EUS 3, and EUS 4. The EUS 2 ORF is 1146 nucleotides (nt) in length and encodes a potential protein of 382 amino acids. Cis-regulatory sequences upstream of the putative ATG start codon include a G/C box 112 nt upstream and two potential TATA-like elements located between 15 and 90 nt before the ATG. The EUS 2 translation product exhibits significant homology to Ser/Thr protein kinases encoded within the Us segments of other herpesviruses, such as herpes simplex virus (26% homology) and pseudorabies virus (PRV), (45% homology), and possesses sequence domains conserved in protein kinases of cellular and viral origin. The EUS 3 ORF begins 127 nt downstream from the EUS 2 stop codon and ends at a stop codon 1119 nt further downstream. A single TATA-like element maps 61 nt upstream of the ORF. This ORF encodes a potential protein of 373 amino acids and is a homolog of glycoprotein gX of PRV, as judged by overall homology of amino acid residues, cysteine displacement, and presence of potential glycosylation sites and signal sequence. Interestingly, the EUS 4 ORF encodes a potential membrane glycoprotein that does not exhibit homology to any reported protein sequence. The EUS 4 ORF encodes a 383 amino acid polypeptide with a sequence indicative of a signal sequence at its amino terminal end, glycosylation sites for N-linked oligosaccharides, and a transmembrane domain near its carboxyl terminus. Several cis-acting regulatory sequences lie upstream of this ORF. These findings support the observation that the short region of alphaherpesviruses show considerable variation in their genetic content and gene organization.


Effect of capping protein on the kinetics of actin polymerization.
Acanthamoeba capping protein increased the rate of actin polymerization from monomers with and without calcium. In the absence of calcium, capping protein also increased the critical concentration for polymerization. Various models were evaluated for their ability to predict the effect of capping protein on kinetic curves for actin polymerization under conditions where the critical concentration was not changed. Several models, which might explain the increased rate of polymerization from monomers, were tested. Two models which predicted the experimental data poorly were (1) capping protein was similar to an actin filament, bypassing nucleation, and (2) capping protein fragmented filaments. Three models in which capping protein accelerated, but did not bypass, nucleation predicted the data well. In the best one, capping protein resembled a nondissociable actin dimer. Several lines of evidence have supported the idea that capping protein blocks the barbed end of actin filaments, preventing the addition and loss of monomers [Cooper, J. A., Blum, J. D., & Pollard, T. D. (1984) J. Cell Biol. 99, 217-225; Isenberg, G. A., Aebi, U., & Pollard, T. D. (1980) Nature (London) 288, 455-459]. This mechanism was also supported here by the effect of capping protein on the kinetics of actin polymerization which was nucleated by preformed actin filaments. Low capping protein concentrations slowed nucleated polymerization, presumably because capping protein blocked elongation at barbed ends of filaments. High capping protein concentrations accelerated nucleated polymerization because of capping protein's ability to interact with monomers and accelerate nucleation.


Metalworking fluid bioaerosols at selected workplaces in a steelworks.
Exposure to metalworking fluid (MWF) aerosols has been shown to be associated with a variety of respiratory and skin diseases of workers. Measurements of particulate aerosols, bacterial bioaerosol, and endotoxins and 3-hydroxy fatty acids (3-OH FAs) content in water-based and straight oil MWFs were done during an 8 hr work shift in the grindery and oil basement sections of a steelworks located in Upper Silesia, Poland. Particulate aerosol concentrations were below NIOSH recommended occupational exposure level. Differences in concentration and taxonomical composition of airborne bacteria between grindery and oil basement were found, due to the more aggressive creation of oil mist during machining operations and different MWF characteristics, which favor growth of different bacterial strains. The GC-MS analysis of 3-OH FAs as a marker of endotoxin contamination of the MWF and of the air seems to be a promising tool for evaluation of occupational exposure to bacterial bioaerosols.


Maternal experiences of caring for a child with a ventricular assist device.
The purpose of this study was to gain a deeper understanding of maternal experiences of caring for their child with a VAD at home as a bridge to transplant. A descriptive, qualitative study was conducted via telephone-recorded guided interviews. Participants were caring for or had a child with a VAD between 4 and 16 years old. Data collection occurred over a 12-month period. Using the snowball sampling technique, a purposeful sample of mothers (n = 6) was consented and completed the interview. The data were analyzed using an iterative process of thematic analysis. Five themes emerged: physical modifications, the loss of independence, the emotional rollercoaster, support from others, and transitions on and off the device. We introduced new evidence about sleep, contraception, and heart transplantation, and how VAD therapy impacts childhood development. The mean duration of VAD support was 263 ± 170 days. Five children had heart transplants by the time of interview. To the best of our knowledge, this is the first qualitative study in the US that explores maternal experiences of caring for a child who is living at home with a VAD. VAD therapy is a novel approach to managing advanced heart failure among children and presents unique challenges when caring for them at home. Results provide insight into the education, physical environment, and support needed by parents.


A single-suture technique for placement of the ganciclovir implant.
The ganciclovir implant is a surgically implanted sustained-release drug delivery system used for the treatment of cytomegalovirus retinitis. The device is suspended in the vitreous cavity through a pars plana incision. Previous reports of the surgical procedure have described securing the implant on 1 suture, tied with an external knot. The ends of this suture were left long to avoid sharp ends eroding through the conjunctiva. The wound was then closed with 1 or more additional sutures, with the ends tied and cut short. We describe a technique whereby the wound is closed and the implant secured with a single running suture. The advantages of this technique include efficiency and elimination of exposed knots. We have observed no complications attributable to this technique.


Flaxseed bioactive compounds change milk, hormonal and biochemical parameters of dams and offspring during lactation.
We evaluated maternal intake of SDG (secoisolariciresinol diglucoside), a compound from flaxseed, and flaxseed oil+SDG on biochemical and hormonal parameters of dams and male and female offspring during lactation. Dams were fed a standard diet (C); diet added 40 mg of SDG/100g diet (SDG) or diet added 40 mg of SDG/100g diet and 7% of flaxseed oil (OLSDG). SDG and OLSDG dams showed hyperprolactinemia. The OLSDG milk had lower lactose and protein, while the SDG milk had lower protein on the 14th day of lactation. At 14 days, OLSDG male and female pups showed lower body mass, SDG and OLSDG male pups had hypoprolactinemia and lower body fat mass, but higher visceral fat mass (VFM) and hypertriglyceridemia. At 21 days, male SDG and OLSDG presented hypotriglyceridemia. At 14 days, SDG and OLSDG female offspring showed higher serum 17-β estradiol (E2); OLSDG presented hypercholesterolemia and SDG presented hypertriglyceridemia. At 21 days, SDG and OLSDG female pups showed hypotriglyceridemia and OLSDG shower lower E2. Both maternal treatments changes maternal metabolism as well as hormonal and biochemical parameters of the offspring, which are gender-dependent. Maternal hyperprolactinemia may act as an imprint factor responsible for the hormonal and metabolic changes observed in the pups.


Brugada type 1 electrocardiographic pattern induced by severe hyponatremia.
Brugada syndrome is characterized electrocardiographically by ST segment elevation in the right precordial leads, followed by a negative T wave unrelated to ischemia, electrolyte disturbance or drug effects and prone to rapid polymorphic ventricular tachycardia capable of degenerating into ventricular fibrillation. The ECG pattern may be dynamic and is often concealed. Sodium channel blockers, drugs, electrolyte imbalances, fever and several other clinical circumstances are recognized inducers of a Brugada type 1 ECG in susceptible patients. We describe a case of a Brugada type 1 ECG pattern induced by severe hyponatremia.


Hydroxyethylstarch administration does not depress reticuloendothelial function or increase mortality from sepsis.
Hydroxyethylstarch (HES) is being used increasingly in clinical hemorrhagic shock. Since patients in shock are at high risk of subsequent infection, concern has been voiced about possible adverse effects of HES on the reticuloendothelial system (RES) and host defenses against sepsis. We examined this issue in male albino Holtzman rats given HES or saline (60 ml/kg) i.v. RES function was evaluated 24 and 48 h after HES administration by measuring the intravascular clearance rates (t/2) and organ retention of 131I-triolein lipid emulsion. Neither the intravascular clearance rates nor organ retention of the lipid emulsion was affected at 24 or 48 h after HES. In another group of rats, sepsis was produced by cecal ligation and puncture 2 d after HES or saline infusion. The survival rates were 41% and 43%, respectively, in the saline- and HES-treated animals. These studies reveal no deleterious effects of a clinically relevant volume of HES on either RES function or host resistance to sepsis.


Galectin-1 reduced the effect of LPS on the IL-6 production in decidual cells by inhibiting LPS on the stimulation of IκBζ.
Pregnancy is a complex process where several physiological pathways interact. The down-regulated inflammatory response and the abundance of anti-inflammatory molecules during gestation may explain the acceptance of the fetus and the lack of immune response against it, even though it is a foreign tissue for the mother. NF-κB is a key regulator of the transcription of inflammatory genes, such as IL-8, IL-1β, TNF-α, or IL-6. Increased NF-κB activity that leads to the production of proinflammatory cytokines may induce obstetric disorders, such as preterm birth or abortion. Low activity of this transcription factor is associated with the beneficial anti-inflammatory environment during fetus development until delivery. Galectin-1 (Gal-1) is a lectin-type glycan-binding protein that is able to down-regulate inflammation. It has been shown that Gal-1 is abundantly expressed at the feto-maternal interface in humans, where it promotes maternal immune tolerance to the fetal semi-allograft. Gal-1 tolerance-promoting mechanisms have been established for adaptive immune cells, such as T cells and dendritic cells. However, the role of this lectin has not been established in non-immune cells at the feto-maternal interface. Here, we determined that Gal-1 is able to block the stimulating effect of LPS on IL-6 in human decidua cells. Our results show that Gal-1 acts by inhibiting the stimulation of the LPS-induced IκBζ expression, an NF-κB regulator involved in IL-6 gene transcription.


Tissue and plasma levels of immunoreactive gastrin and cholecystokinin in chickens with and without bombesin.
Immunoreactive gastrin and immunoreactive cholecystokinin were measured in chicken tissue extracts obtained from the gut and brain. In contrast to that found in mammals, immunoreactive gastrin found in chickens was higher in the brain than in gut tissues, and it was highest in the ileum when compared with other gut tissues. Dose-response curves of tissue extracts from the brain and ileum and of serum were parallel to the dose-response curve of synthetic human gastrin, suggesting the existence of gastrin or a peptide immunologically similar to gastrin in those chicken tissues. Immunoreactive cholecystokinin in tissues was highest in the duodenum, followed by the jejunum, ileum, and cortex; lesser amounts of cholecystokinin were found in other tissues. Influence of bombesin on the release of immunoreactive gastrin and immunoreactive cholecystokinin in the blood of chickens was also studied. Bombesin doses of 3 micrograms/kg per hour significantly increased immunoreactive gastrin in serum and immunoreactive cholecystokinin in plasma, whereas gastrin did not increase with a bombesin dose of 0.6 micrograms/kg per hour. The results confirm the existence of immunoreactive gastrin and immunoreactive cholecystokinin in the tissue of chickens and indicate that they are released into circulation in response to bombesin.


[Pathophysiological and therapeutic aspects of bone lesions in patients with multiple myelomas].
Multiple myeloma (MM) is an uncontrolled malignant proliferation of plasma cells. Today, it is the best studied form of hemoblastomas, but many pathophysiological and therapeutic aspects of this condition await a deeper insight. The medico-social significance of the disease is emphasized by its continuous growth, variable clinical manifestations, low quality of the patients" life, mean life expectancy of 3-5 years, and numerous complications. One clinical feature of MM is bone lesions that occur in all patients as osteolysis (OL), osteoporosis (OP), hypercalcemia, and combination of these disorders. Progressive degeneration of bone tissue even in patients responding to chemotherapy results in severe pain, pathological fractures, and neurologic problems. Molecular mechanisms of OL and OP in MM have recently attracted much attention. This review summarizes data on the role of cytokines, growth factors, osteopontin, OPG-RANK-RANK system, macrophage inflammatory proteins, and matrix metalloproteinases in MM-related osteodestruction. Iatrogenic origin of bone lesions is considered. Treatment of MM using thalidomide (lenlalidomide), proteasome inhibitors (bortesamide), and biphosphonates (pamidronate, zoledronic acid) is discussed as the most promising therapeutic strategy promoting plasma cell apoptosis, inhibition of bone resorption, stabilization of osteoblast function, and pain alleviation.


Dermoscopic diagnosis of melanoma in a 4D space constructed by active contour extracted features.
Dermoscopy, also known as epiluminescence microscopy, is a major imaging technique used in the assessment of melanoma and other diseases of skin. In this study we propose a computer aided method and tools for fast and automated diagnosis of malignant skin lesions using non-linear classifiers. The method consists of three main stages: (1) skin lesion features extraction from images; (2) features measurement and digitization; and (3) skin lesion binary diagnosis (classification), using the extracted features. A shrinking active contour (S-ACES) extracts color regions boundaries, the number of colors, and lesion's boundary, which is used to calculate the abrupt boundary. Quantification methods for measurements of asymmetry and abrupt endings in skin lesions are elaborated to approach the second stage of the method. The total dermoscopy score (TDS) formula of the ABCD rule is modeled as linear support vector machines (SVM). Further a polynomial SVM classifier is developed. To validate the proposed framework a dataset of 64 lesion images were selected from a collection with a ground truth. The lesions were classified as benign or malignant by the TDS based model and the SVM polynomial classifier. Comparing the results, we showed that the latter model has a better f-measure then the TDS-based model (linear classifier) in the classification of skin lesions into two groups, malignant and benign.


Beta-cell function and visceral fat in lactating women with a history of gestational diabetes.
Lactation has been recommended as beneficial for the maternal metabolic abnormalities associated with glucose intolerance and diabetes risk, although associations between breastfeeding (BF), glucose tolerance, and adipose tissue distribution are unknown. Therefore, a population of women with recent gestational diabetes (GDM) was evaluated with comparison of results for lactating versus nonlactating women. A total of 26 women participated (14 BF and 12 nonbreastfeeding [nonBF]) with a singleton vaginal delivery after 36 weeks gestation. At 3 months postpartum, each woman completed a 75-g oral glucose tolerance test (OGTT), a frequently sampled intravenous glucose tolerance test (FSIGT), and computed tomography (CT) scanning for adipose distribution and mass. Insulin sensitivity was not significantly different between BF and nonBF groups (4.97 +/- 0.78 v 3.44 +/- 1.0 x 10(-4) min(-1)/(microU/mL) nor was glucose effectiveness (1.92 +/- 0.22 v 1.56 +/- 0.19 x 10(-2) min(-1)). However, the disposition index (DI) (insulin sensitivity [S(I)] x acute insulin response to glucose [AIRg]) was higher in the BF group (129.9 +/- 26.0 v 53.4 +/- 18.0 x 10(-4) min(-1); P =.03). Visceral fat (103 +/- 14 v 97 +/- 15 cm(2)) and subcutaneous fat (362 +/- 36 v 460 +/- 68 cm(2)) were similar between the groups. We conclude that 3 months of BF in a population with previous GDM was associated with improved pancreatic beta-cell function, but not with any difference in measures of adiposity.


Two-photon-excited fluorescence enhanced by a surface plasmon.
We demonstrate a technique that utilizes surface-plasmon resonance to intensify the fluorescence produced by multiphoton excitation. By enhancing the electric field initially generated by the excitation laser light, the presence of plasmon resonance introduces a gain 90 times higher in the experimentally observed fluorescence intensity than that produced from total internal reflection fluorescence. We also analyze the enhancement efficacy of surface-plasmon resonance as a function of the excitation wavelength.


Lupus erythematosus: clinical and histopathological study of oral manifestations and immunohistochemical profile of the inflammatory infiltrate.
Lupus erythematosus (LE) is a multifactorial autoimmune disease, which may affect the oral mucosa in either its cutaneous and systemic forms, with varied prevalence. Forty-six patients with confirmed diagnosis of LE, presenting oral lesions were included in the study. Oral mucosal lesions were analyzed clinically, their histopathological features were investigated and inflammatory infiltrate constitution was assessed using immunohistochemistry against the following clusters of differentiation: CD3, CD4, CD8, CD20, CD68 and CD1a. From 46 patients with specific LE oral lesions 34 were females (25 with cutaneous LE and nine with systemic LE) and 12 were males (11 with cutaneous LE and one with systemic LE). Clinical aspects of lesions varied, and lips and buccal mucosa were the most affected sites. Histologically, lesions revealed lichenoid mucositis with perivascular infiltrate and thickening of basement membrane. Inflammatory infiltrate was predominantly composed by T lymphocytes of the CD4 subtype, with a minor prevalence of B lymphocytes, isolated macrophages and rare Langerhans cells. Oral lesions of lupus erythematosus show a variety of clinical aspects and histologically consist of a lichenoid mucositis with deep inflammatory infiltrate, composed predominantly of T CD4 positive lymphocytes.


Pretreatment with transmyocardial revascularization might improve ischemic myocardial function performed with cell transplantation.
Cells transplanted into the myocardial infarct areas might be lost because of the lack of blood supply to these myocardium areas. The hypothesis that pretreatment with angiogenic therapy induced by transmyocardial revascularization (TMR) might improve ischemic myocardial function, followed by cell transplantation was tested. After the ligation of the left anterior descending coronary artery, rats were treated with TMR. Two weeks, embryonic stem cells were transplanted into an injured heart. Four weeks after cell transplantation, cardiac function was assessed by homodynamic measurements. Capillary density and infarct size in the infarct myocardium were measured by using a previous experimental method. Graft histology and morphology was also evaluated. Four weeks after the operation, myocardial infarct (MI) rats treated with TMR and cell transplantation showed significantly higher cardiac function in hemodynamic measurements (p < 0.01) than that of MI rats receiving cell transplantation or TMR alone. A significant increase in capillary density and reduction in infarct size was observed in the MI rats that received a combined therapy (p < 0.01). Pretreatment of an infarct region of the heart with angiogenesis induced by TMR can enhance the efficacy of a cell graft and attenuate the progression of cardiac dysfunction in the rat model.


MicroRNAs: A New Understanding of Platelet Physiology and Pathology.


Sleep and critical care.
Sleep distortion has been studied as an independent risk factor for morbidity and mortality; however, this role in the ICU patients is unclear. These patients suffer from psychological and physiological stressors and significant disturbance in sleep. We conducted a systematic review of all recent data over the last decade to elaborate the extent and implications of sleep disruption in the ICU. Despite adequate data proving that ICU patients have poor quality of sleep over the last three decades, the implications of the sleep distortion in this patient population remains misunderstood. Recently, the Whitehall cohort trial has raised interest in sleep and mortality and substantial data have surfaced regarding prevalence of sleep disturbance in the ICU. This article discusses the available data on sleep disruption in patients in the ICU and implications with discussion of effects of ventilators and commonly used medications in the ICU. We will conclude with interventions to improve sleep in the intensive care setting.


Viral hepatitis.
Hepatitis A is still the most frequently reported vaccine preventable disease. A reduction in the incidence will only be achieved by routine childhood vaccination rather than by targeted vaccination of high-risk groups. A larger vaccine program is warranted. Hepatitis B remains a large public health problem. Vaccination targeted to high-risk adults failed to decrease the incidence of hepatitis B virus (HBV) infection. Sexual as well as nosocomial transmission remain serious problems. Vaccine escape variants have also been identified in newborns from infected mothers who had been vaccinated at birth. Clearance of HBV infection results from complex immune mechanisms including TH1 cytokines significantly associated with HLA class II alleles. Escape HBV mutants, especially precore mutants, influence the outcome. The sequences of the promoter and other critical regions were associated with severe activity. Lamivudine is a major advance in therapy of chronic hepatitis B which was recently approved in many countries. Although drug resistant mutants may be selected during therapy, additional nucleoside analogues including adefovir are promising. Optimal combination strategies of different active compounds need to be researched. Three per cent of the world population has been infected with hepatitis C virus (HCV). Epidemiology has shifted from transfusion to non-transfusion settings. Intravenous drug abuse is currently the main risk but nosocomial infection is also of concern. Three independent factors seem associated with fibrosis progression: age, daily alcohol consumption of 50 g or more and male gender. Median duration of progression to cirrhosis is about 30 years. At the cirrhotic stage, about 3-5% of patients per year develop hepatocellular carcinoma. There is little evidence that direct cytopathicity plays a significant role in liver cell injury. HCV also infects extrahepatic cells which seems critical in the pathogenesis of the many extrahepatic manifestations. The recent identification of CD81 protein as one of the HCV receptor candidates may help us to understand how chronic HCV infection may trigger a wide spectrum of clinical manifestations, autoimmune or even lymphoproliferative, through potent continuous B cell activation in the context of various host and/or environmental cofactors. Direct measurement of HCV RNA has clarified HCV replication kinetics and variability. Among patients with chronic hepatitis C, 48 weeks of treatment with interferon/ribavirin therapy produced a response rate of 28% among those with genotype 1 and 66% with other genotypes. Similar differences were found for combination therapy among patients who had relapsed following previous interferon (IFN) therapy. Viral load prior to treatment has been clearly shown to be predictive of response to interferon treatment, with increased viral load associated with decrease rates of response. In patients non-responsive to interferon, a second course of interferon alone has no beneficial effect whereas combination therapy may induce response in 25%. In conclusion, combination therapy should be given in all situations. Viral eradication should not be the only objective of the treatment since histological improvement may be obtained despite persisting viral replication with prolonged maintenance of antiviral therapy.


A microcomputer model of contaminant transport in an aquatic system.
A micro computer model was developed for routing chemical waste contamination through a small aquatic system. The capabilities of this simulation model include the following characteristics: a) It distributes contamination by advection and dispersion along the longitudinal axis of the system. b) It may be discretized into any number of segments (vertical planes normal to the longitudinal axis) as may be appropriate to describe spatial variations in chemical contamination. c) It is capable of treating instantaneous, continuous, or time varying releases of chemical waste contamination. d) It provides for temporal description of contamination throughout the system. e) It provides for adsorption and desorption by both vegetation and bottom sediments. The model can be run on microcomputer with Fortran compiler. The model applied to two small streams which are located in U.S.A., and Canada. The model results compared well with observed data. The dispersion parameter was computed by the model.


Crucial role of the biological barrier at the primary targeted organs in controlling the translocation and toxicity of multi-walled carbon nanotubes in the nematode Caenorhabditis elegans.
Multi-walled carbon nanotubes (MWCNTs) can be translocated into the targeted organs of organisms. We employed a model organism of the nematode Caenorhabditis elegans to investigate the role of a biological barrier at the primary targeted organs in regulating the translocation and toxicity formation of MWCNTs. A prolonged exposure to MWCNTs at predicted environmental relevant concentrations caused adverse effects associated with both the primary and secondary targeted organs on nematodes. The function of PEGylated modification in reducing MWCNTs toxicity might be mainly due to the suppression of their translocation into secondary targeted organs through the primary targeted organs. A biological barrier at the primary targeted organs contributed greatly to the control of MWCNTs translocation into secondary targeted organs, as indicated by functions of Mn-SODs required for prevention of oxidative stress in the primary targeted organs. Over-expression of Mn-SODs in primary targeted organs effectively suppressed the translocation and toxicity of MWCNTs. Our work highlights the crucial role of the biological barrier at the primary targeted organs in regulating the translocation and toxicity formation of MWCNTs. Our data also shed light on the future development of engineered nanomaterials (ENMs) with improved biocompatibility and design of prevention strategies against ENMs toxicity.


Incorporating additional targets into learning trials for individuals with autism spectrum disorder.
Recently, researchers have investigated the effectiveness and efficiency of presenting secondary targets during learning trials for individuals with autism spectrum disorder (ASD). This instructional method may be more efficient than typical methods used with learners with ASD, because learners may acquire secondary targets without additional instruction. This review will discuss the recent literature on providing secondary targets during teaching trials for individuals with ASD, identify common aspects and results among these studies, and identify areas for future research.


Longitudinal changes in adjustment after spinal cord injury: a 15-year study.
Research on changes in adjustment after spinal cord injury (SCI) has produced mixed results. Whereas cross-sectional research has suggested that adjustment declines with increasing age, but improves with greater time since injury, longitudinal research has suggested that some limited positive changes in adjustment occur over an 11-year period. The purpose of the current study was to identify the stability of adjustment over a 15-year period after SCI. One hundred thirty-five participants with SCI completed Life Situation Questionnaires (LSQ) in both 1974 and 1989. T-test comparisons were made on five adjustment scales and 15 individual items. The results suggested several positive changes in adjustment during the 15 years including increased sitting tolerance, more years of education, greater satisfaction with finances and employment, and a higher percentage of persons working. Decreases were noted in the number of hospitalizations and the number of days hospitalized. Given the average number of years since injury (9.3 years in 1974; 24.3 years in 1989), the results suggest that adjustment will at worst be stable, and at best will improve significantly with time.


Changes in blood levels of zinc, copper, selenium, glutathione peroxidase, vitamin B12 and total and free thyroxine in sheep removed from pasture and held without food for 50 hours.
Blood was collected from a group of ten sheep immediately after removal from pasture and thereafter at regular intervals for 50 hours whilst maintaining them without food but with adequate water. The samples were analysed for parameters normally examined as an aid to the diagnosis of zinc, copper, selenium, cobalt and iodine status. Serum vitamin B12 levels increased with time. Mean plasma zinc concentrations and mean serum concentrations of both T4 and fT4 followed significant parabolic trends. Maximum mean zinc levels (50 +/- 10% higher than initial values) were recorded after 30 hours. T4 and fT4 levels peaked at approximately 26 hours. Zinc levels at two hours were 20 +/- 5% lower than the initial values. Whole blood copper, selenium and glutathione peroxidase levels did not change significantly with time the largest differences were 11 +/- 6%, 5 +/- 4% and 10 +/- 8% respectively.


Moraxella lacunata isolated from epidemic conjunctivitis among teen-aged females.
An epidemic follicular conjunctivitis affecting teen-aged females has been studied. Moraxella lacunata was isolated from 11% of the patients, a frequency far above the rate found in other types of chronic conjunctivitis. The condition is suggested to be the chronic follicular conjunctivitis (Axenfeld) due to Moraxella lacunata.


Marketing the nursing practice of obstetrics.
This article offers nurses a conceptual framework for marketing their skills and discusses how that framework can be applied to obstetric nursing practice. A thorough understanding of the framework presented will provide maternity nurses with the foundation they need to participate effectively in a marketing plan. Examples of the application of the framework to specific clinical situations are examined.


Microbial ecology of drinking water distribution systems.
The supply of clean drinking water is a major, and relatively recent, public health milestone. Control of microbial growth in drinking water distribution systems, often achieved through the addition of disinfectants, is essential to limiting waterborne illness, particularly in immunocompromised subpopulations. Recent inquiries into the microbial ecology of distribution systems have found that pathogen resistance to chlorination is affected by microbial community diversity and interspecies relationships. Research indicates that multispecies biofilms are generally more resistant to disinfection than single-species biofilms. Other recent findings are the increased survival of the bacterial pathogen Legionella pneumophila when present inside its protozoan host Hartmannella vermiformis and the depletion of chloramine disinfectant residuals by nitrifying bacteria, leading to increased overall microbial growth. Interactions such as these are unaccounted for in current disinfection models. An understanding of the microbial ecology of distribution systems is necessary to design innovative and effective control strategies that will ensure safe and high-quality drinking water.


Factors influencing the efficacy of virtual reality distraction analgesia during postburn physical therapy: preliminary results from 3 ongoing studies.
To assess the efficacy and side effects of immersive virtual reality (VR) distraction analgesia, as well as patient factors associated with VR analgesic efficacy in burn patients who require passive range-of-motion (ROM) physical therapy (PT). Prospective, randomized, controlled, within-subject trials. Regional level I burn center in a university-affiliated urban hospital. Patients (age range, 6-65y) who required passive ROM PT in sessions lasting 3 to 15 minutes after cutaneous burn injury. Standard analgesic (opioid and/or benzodiazepine) care and standard analgesic care plus immersive VR distraction. Self-reported subjective pain ratings (0 to 100 graphic rating scale). A total of 146 treatment comparisons were made in 88 subjects, 75% of whom were children ages 6 to 18 years. Compared with standard analgesic treatment alone, the addition of VR distraction resulted in significant reductions in subjective pain ratings for worst pain intensity (20% reduction), pain unpleasantness (26% reduction), and time spent thinking about pain (37% reduction). Subjects' age, sex, ethnicity, size of initial burn injury, or duration of therapy session did not affect the analgesic effects of VR distraction. Nausea with the standard care plus VR distraction condition was infrequent (15%) and mild, with 85% of the subjects reporting no nausea. Children provided higher subjective reports of "presence" in the virtual environment and "realness" of the virtual environment than did adults, but age did not affect the analgesic effects of VR distraction. When added to standard analgesic therapy, VR distraction provides a clinically meaningful degree of pain relief to burn patients undergoing passive ROM PT. Multiple patient factors do not appear to affect the analgesic effect. Immersive VR distraction is a safe and effective nonpharmacologic technique with which to provide adjunctive analgesia to facilitate patient participation in rehabilitation activities.


Epidemiology of malpractice lawsuits in paediatrics.
A systematic review of malpractice lawsuits involving children identified six articles and 227 cumulative paediatric published cases. The prevalence of medical lawsuits resulting in payment to plaintiff was found to be 50% less frequent than that in adults. The most frequent and severe errors were among infants, including diagnostic errors of meningitis, gastroenteritis and pneumonia. The most implied unit was emergency department (58%). The patients and/or families were compensated in 23- 68% of cases. These data can increase physicians' awareness of disorders and age groups at high risk of medical errors. This could lead to minimize the risk of medical malpractices and to improve patient safety.


PATHOGENESIS OF CUSHING DISEASE: AN UPDATE ON THE GENETICS OF CORTICOTROPINOMAS.
Cushing disease is a rare severe condition caused by pituitary tumors that secrete adrenocorticotropic hormone (ACTH), leading to excessive endogenous glucocorticoid production. Tumors causing Cushing disease, also called corticotropinomas, are typically monoclonal neoplasms that mainly occur sporadically. Literature review. Cushing disease is very rarely encountered in genetic familial syndromes. Oncogenes and tumor suppressor genes commonly associated with other tumor types are only rarely mutated in this tumor type. The advent of next-generation sequencing led to the identification of a single mutational hotspot in the ubiquitin-specific protease 8 ( USP8) gene in almost half of Cushing disease tumors. The new discoveries showcase a novel mechanism responsible for corticotroph tumorigenesis and ACTH hypersecretion and highlight USP8 and its downstream signaling pathways as potential promising pharmacologic targets for the management of Cushing disease. ACTH = adrenocorticotropic hormone; BRG1 = Brahma-related gene 1; CABLES1 = CDK5 and ABL1 enzyme substrate 1; CD = Cushing disease; CNC = Carney complex; DICER1 = cytoplasmic endoribonuclease III; EGFR = epidermal growth factor receptor; GR = glucocorticoid receptor; IL = interleukin; MEN = multiple endocrine neoplasia; miRNA = microRNA; POMC = proopiomelanocortin; SSTR = somatostatin receptor; USP8 = ubiquitin-specific protease 8.


Analysis methods for new work cell standards. Risk analysis and risk reduction help in dealing with the revised Robot Standard.
The final reiterative loop of risk reduction leads to residual risk, sometimes called "tolerable risk." This is the risk with which one must live, and is typically handled through proper training, signage and personnel protective clothing. Any existing safeguards should be considered removed when performing a risk analysis. This will allow the full impact of the resulting tolerable risk (initial risk--risk reduction) to be more accurately evaluated. Trying to walk the fine line between the cost of making machine processes safe and the economics of staying competitive is not easy, and it is not the intent of the regulatory bodies to put companies out of business. However, a good rule of thumb with respect to OSHA is that if a machine process can be guarded, guard it. Otherwise the ultimate test of residual risk may be in the litigation.


Clinical characteristics related to severity of sexual abuse: a study of seriously mentally ill youth.
In this study we examined demographic, social, and clinical variables related to sexual abuse histories in a sample of severely mentally ill youth. Data were collected via a retrospective chart review of all patients treated over a 5-year period (1987-1992) at a tertiary care public sector psychiatric hospital. The sample was divided into four groups: no history of sexual abuse (n = 226); isolated events (n = 62); intermittent abuse (n = 61); and chronic (n = 150). Youth with sexual abuse histories were more often female, had higher rates of social chaos and associated physical abuse and neglect, and had higher rates of post-traumatic stress disorder (PTSD) and substance abuse disorders. Chronically abused subjects came from the most chaotic and abusive backgrounds; were younger when first abused; had the highest number of abusers; were more likely to have been molested; and were more often abused by their father/stepfather and/or their mother/stepmother. Using logistic regression analyses, sexual abuse histories were predicted by sexually inappropriate behaviors, symptoms of PTSD and borderline personality disorders, dissociative symptoms, substance abuse and animal cruelty. Sexual abuse histories were quite common in this sample. Sexually abused subjects had increased rates of inappropriate sexual behaviors, substance abuse, and post-traumatic reactions; and were frequently exposed to other confounding environmental risk factors, including physical abuse, family problems and social chaos.


Endothelial precursor cells in the synovial tissue of patients with rheumatoid arthritis and osteoarthritis.
To find evidence for the presence of endothelial precursor cells, which can induce new vessel formation, in the synovial tissue of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Precursor cells in the synovial tissue of 18 RA patients and 15 OA patients were identified by immunohistochemistry, morphometric analysis, and confocal laser scanning microscopy using the following phenotype markers: CD31, CD34, STRO-1, CD133, vascular endothelial growth factor receptor 2 (VEGFR-2), and CXCR4. The presence of CD31, CD34, CD133, VEGFR-2, and CXCR4 messenger RNA in the synovial tissue was determined by reverse transcriptase-polymerase chain reaction, and the message for CXCR4 was quantified by an RNase protection assay. A population of cells that expressed CD34 on their surface but lacked the endothelial cell marker CD31 was found in the synovial tissue of RA and OA patients. CD34+,CD31- cells were detected in close proximity to STRO-1+ and CD133+ cells, forming cell clusters in the sublining area of the synovial membrane. Within these cell clusters, CD34+,CD31- precursor cells were located on the inside surrounded by STRO-1+ cells and with CD133+ cells on the outside. CD34+ precursor cells in the cell layer expressed high levels of the chemokine receptor CXCR4, while VEGFR-2 was expressed on CD34+ and CD133+ cells, and alpha-smooth muscle actin was expressed on STRO-1+ cells. The presence of endothelial precursor cells in the synovial tissue of RA and OA patients provides evidence for vasculogenesis induced by precursor cells that arise in situ or from circulating progenitors.


A bimodal modulation of the cAMP pathway is involved in the control of myogenic differentiation in l6 cells.
We have previously shown that myogenesis induction by Arg8-vasopressin (AVP) in L6 rat myoblasts involves a sustained stimulation of type 4 cAMP-phosphodiesterase. In this model, we observed that a transient cAMP generation occurs in the minutes following AVP addition. Evidence suggests that cAMP generation is due to the prostaglandins produced in response to AVP binding to V1a receptors and subsequent activation of phospholipase A2. The early cAMP increase was effective in activating cAMP-dependent protein kinase (PKA) and increasing phosphorylation of CREB transcription factor. Inhibition of PKA by compound H89 prior to AVP addition led to a significant reduction of expression of the differentiation marker creatine kinase, whereas H89 added 1-5 h after AVP had no significant effect. Furthermore, PKA inhibition 24 h after the beginning of AVP treatment potentiated differentiation. This shows that both an early activation and a later down-regulation of the cAMP pathway are required for AVP induction of myogenesis. Because phosphodiesterase PDE4D3 overexpressed in L6 cells lost its ability to potentiate AVP-induced differentiation when mutated and rendered insensitive to PKA phosphorylation and activation, we hypothesize that the early cAMP increase is required to trigger the down-regulation of cAMP pathway through stimulation of phosphodiesterase.


Bovine serum albumin (BSA) nephritis in rats. VII. In vivo kinetics of polymorphonuclear leukocytes.
In vivo quantitation of polymorphonuclear leukocytes (PMN) was carried out and their accumulation kinetics were determined by adoptive transfer of 51Cr-PMN in control rats, nephritic but non-proteinuric rats and nephritic rats with heavy proteinuria. Nephritis was induced by daily administration of antigen to preimmunized rats for 4 weeks. Renal accumulation of 51Cr-PMN was maximal at 3 h after the adoptive transfer in diseased rats, to which the last antigen administration was given 24 h prior to the kinetic study. Histologically, however, a considerable number of PMN had infiltrated into the glomeruli of these rats at any given time during the 24-h period, i.e., the time interval between antigen challenges. Two pieces of evidence strongly suggest that circulating PMN adhere to glomeruli, stay there for a short time and then become dispersed again into the circulation. When antigen was administered after 51Cr-PMN transfer, the PMN disappeared promptly from the circulation and accumulated in the lungs and liver, resulting in a lack of any peak in the kidney PMN kinetics. It is concluded that the presence of an appreciable number of PMN in the glomeruli reflected the dynamic balance of cell influx and efflux.


Cardiovascular and fluid volume control in humans in space.
The human cardiovascular system and regulation of fluid volume are heavily influenced by gravity. When decreasing the effects of gravity in humans such as by anti-orthostatic posture changes or immersion into water, venous return is increased by some 25%. This leads to central blood volume expansion, which is accompanied by an increase in renal excretion rates of water and sodium. The mechanisms for the changes in renal excretory rates include a complex interaction of cardiovascular reflexes, neuroendocrine variables, and physical factors. Weightlessness is unique to obtain more information on this complex interaction, because it is the only way to completely abolish the effects of gravity over longer periods. Results from space have been unexpected, because astronauts exhibit a fluid and sodium retaining state with activation of the sympathetic nervous system, which subjects during simulations by head-down bed rest do not. Therefore, the concept as to how weightlessness affects the cardiovascular system and modulates regulation of body fluids should be revised and new simulation models developed. Knowledge as to how gravity and weightlessness modulate integrated fluid volume control is of importance for understanding pathophysiology of heart failure, where gravity plays a strong role in fluid and sodium retention.


The Sleep Condition Indicator: reference values derived from a sample of 200 000 adults.
The Sleep Condition Indicator (SCI) is an eight-item rating scale that was developed to screen for insomnia disorder based on DSM-5 criteria. It has been shown previously to have good psychometric properties among several language translations. We developed age- and sex-referenced values for the SCI to assist the evaluation of insomnia in everyday clinical practice. A random sample of 200 000 individuals (58% women, mean age: 31 ± 13 years) was selected from those who had completed the SCI via several internet platforms. Descriptive and inferential methods were applied to generate reference data and indices of reliable change for the SCI for men and women across the age deciles 16-25, 26-35, 36-45, 46-55, 56-65 and 66-75 years. The mean SCI score for the full sample was 14.97 ± 5.93. Overall, women scored worse than men (14.29 ± 5.83 versus 15.90 ± 5.94; mean difference: -1.60, η2 = 0.018, Cohen's d = 0.272) and those of older age scored worse than those younger (-0.057 points per year, 95% confidence interval (CI): -0.059 to -0.055) relative to age 16-25 years. The Reliable Change Index was established at seven scale points. In conclusion, the SCI is a useful instrument for clinicians and researchers that can help them to screen for insomnia, compare completers to individuals of similar age and sex and establish whether a reliable change was achieved following treatment.


Haplotype frequency estimation in the presence of genotyping errors.
Several statistical methods have been proposed to estimate haplotype frequencies, either based on unrelated individuals or based on families. These estimates may yield insights on population genetics as well as associations between candidate regions and disease of interest. One limitation of the existing methods is that all these methods make the implicit assumption that there are no genotyping errors. However, genotyping errors are unavoidable in practice. Numerous methods have been developed to incorporate genotyping errors in genetic studies, but none to date have addressed the issues of haplotype inference in the presence of genotyping errors. In this article, we develop statistical methods for haplotype inference incorporating genotyping errors. We describe how our methods can be applied to analyze unrelated individuals as well as nuclear families. Our simulation results show that the proposed methods perform well in the presence of genotyping errors.


Microbial community structure of wastewater treatment subjected to high mortality rate due to ozonation of return activated sludge.
This study investigated the effects of return activated sludge (RAS) ozonation, on the bacterial community structure of pilot-scale wastewater treatment systems. Two parallel activated sludge reactors were operated to treat real municipal wastewater for 98 days. The RAS of one of the reactors was subjected to increasing doses of ozone during the experimental period, which resulted in higher reduction in biosolids waste production and higher bacterial growth rate. The bacterial community structures were investigated by 16S rRNA gene amplicon high-throughput pyrosequencing and fluorescence in situ hybridization (FISH). The structures remained highly similar throughout the experiment despite the ozone treatment. Comparative analyses between pyrosequencing and FISH revealed clear discrepancies in the proportion of some bacterial populations. The results suggest that RAS ozonation is not a main environmental factor structuring the community composition. Instead, the parallel drifts and slight convergence of the two community structures indicate that other environmental factors such as influent wastewater composition and temperature may be more important. Care should be exercised in interpreting the proportion of sequence reads as pyrosequencing may be biased as compared to FISH. This study provides new insights on the importance of indiscriminate high mortality rates brought by external factors (here ozonation) on microbial community structures of activated sludge system.


[Hepatocellular carcinoma treated by intraarterial injection of adriamycin/mitomycin C oil suspension alone or combined with cis-diaminodichloroplatinum].
One hundred thirty-five patients with hepatocellular carcinoma (HCC) were treated by intraarterial injection of adriamycin/mitomycin C oil suspension (ADMOS) alone (59 cases) and ADMOS plus cis-diaminodichloroplatinum (CDDP) (76 cases). Tumor size was reduced by over 25% in 13 of 38 patients (35%) in the ADMOS alone group and in 39 of 76 patients (50%) in the ADMOS plus CDDP group. Serum alpha-fetoprotein (AFP) levels decreased by more than 50% in 7/17 (59%) in the ADMOS alone group and in 23/32 (70%) in the ADMOS plus CDDP group. The overall 1- and 2-year survival rates were 68% and 41% by the Kaplan-Meier method. However, no significant difference in the survival rates was observed between the two groups.


Heterogeneous reactions of isoprene and ozone on α-Al2O3: The suppression effect of relative humidity.
The heterogeneous reactions of α-Al2O3 particles with a mixture of ozone (∼50 ppm) and isoprene (∼50 ppm) were studied as a function of relative humidities (RHs). The reactions were monitored in real time through the microscopic Fourier transform infrared (micro-FTIR) spectrometer. The results show that the presence of ozone leads to the rapid conversion of isoprene to carboxylate (COO-) ions on the surfaces of α-Al2O3 particles in the initial stage. The water significantly suppresses the formation of the carboxylate ions. For the isoprene ozonolysis reaction on the α-Al2O3 particles, the reactive uptake coefficient is strongly suppressed by over a factor of 8 when the RH increases from 8% to 89%. The negative correlation between RH with the secondary organic aerosol (SOA) produced by isoprene ozonolysis plays a key role in the actual atmospheric environment under high humidity. Our results may provide insight into the ozonolysis process of biogenic alkenes over mineral aerosol surfaces with the influence of RHs.


ACOG Committee Opinion. Surgery and patient choice: the ethics of decision making.
The purpose of this Committee Opinion is to provide the obstetrician-gynecologist with an approach to decision making based on ethics in an environment of increased patient information, recognition of patient autonomy, direct-to-consumer marketing, and many alternative or investigational treatments. A process for ethical decision making in surgery is discussed, illustrated by an example of elective cesarean delivery.


[Analysis of the reasons for consultation and dermatology care cost in a primary care site].
The objective of the study was to the visits for esthetic reasons in an out-patient dermatology consultation and their cost and calculate the invoicing of these visits for a site other than the medical specialist consulted. Prospective study in an out-patient dermatology clinic for 12 random days in February 2005. Endpoints of age, gender, diagnosis, cost per visit, cryotherapy and electrocoagulation were collected. Patients were divided into 3 groups: request for esthetic treatment (A), request for dermatology visit (B) and did not come (C). Group B was the largest, with 205 users (46 %), followed by C with 134/455 (29 %) and by A with 116/455 (25 %). In the latter group, the diagnoses were: seborrheic keratosis 39/455 (9 %), acrocordons 21/455 (5 %), remaining diagnoses (intradermal melanocytic nevi, cherry angioma, solar lentigos): 56/116 (11 %). The cost of these visits was 2,528. 8 euros in the 12 days analyzed and treatment of a subgroup of 85 patients (18.75 %) with cryotherapy or electrocoagulation increased it up to 5,043.80 euros. Estimated cost for one year would be 82,950 euros. Calculation of the invoicing for a non-public supplier site to the National Health Service would be: 8769.60 euros/month and 97,875 euros/year. If we add the treatments described, we go from 28,403.40 euros/month to 317,113.80 euros/year. These data and daily experience should make us think about the ethical consequences (do all the patients have to wait the same time?) as well as legal and collective ones (what type of dermatology do we want to specialize in?).


Mechanisms of the bactericidal activity of low amperage electric current (DC).
The mechanisms whereby low amperage (10-100 microA) electric current (DC) is bactericidal were investigated with Staphylococcus epidermidis and Staphylococcus aureus. A zone of inhibition test involving the insertion of an anode and cathode into an agar plate inoculated with a lawn of bacteria was used to study the antimicrobial activity of electric current. A zone of inhibition was produced around the cathode when 10 microA (DC) was applied for 16 h. The diameter of the zone was greatly reduced in the presence of catalase. There was no zone around the cathode when the test was carried out under anaerobic conditions. H2O2 was produced at the cathode surface under aerobic conditions but not in the absence of oxygen. A salt-bridge apparatus was used to confirm that H2O2 was produced at the cathode and chlorine at the anode. The antimicrobial activity of low amperage electric current under anaerobic conditions and in the absence of chloride ions against bacteria attached to the surface of a current carrying electrode was also investigated. Antibacterial activity was reduced under anaerobic conditions, which is compatible with the role of H2O2 as a primary bactericidal agent of electricity associated with the cathode. A reduction in chloride ions did not significantly reduce the antibacterial activity suggesting that chlorine plays only a minor role in the bactericidal activity towards organisms attached to anodal electrode surfaces. The localized production of H2O2 and chlorine and the intrinsic activity due to electric current may offer a useful method for eradicating bacteria from catheter surfaces.


[Biomphalaria glabrata in the state of Piaui].
The occurrence of Biomphalaria glabrata is recorded for the first time in the state of Piaui, where it was collected from several breeding places in the city of Parnaíba. Examination of 694 specimens showed that a part of them were infected with trematodes other than Schistosomatidae. So far no autochthonous cases of schistosomiasis have been identified in the city. The presence of B. glabrata in Parnaíba extends by 20 km eastward its range on the Northern Coastal Region of the Great Northeastern Region of Brazil, where it had been found as far as Araioses, on the eastern extreme of the state of Maranhão.


Oxidation of protein by vaporized sanitizing agents.
For the first time, it has been demonstrated that a protein product can be oxidized readily by certain sanitizing agents through vapor transfer not only in a closed system but also in an open environment. The effect of several sanitizing agents on the oxidation of a model protein, IL-2 mutein, was investigated under different processing conditions. Reversed phase-high performance liquid chromatography (RP-HPLC) was used to separate and quantitate both intact and oxidized IL-2 mutein. It was found that peracetic acid or NaOCl oxidizes IL-2 mutein instantaneously, while H2O2-induced oxidation of IL-2 mutein is much slower in solution. The amount of protein oxidation product is proportional to the duration of sample exposure and the type and concentration of the sanitizing agent. In addition, sanitizing agents can accelerate protein oxidation during lyophilization, and the residual amount can promote oxidation of the lyophilized product during storage. These results strongly suggest that the sanitization process needs to be properly controlled and closely monitored during manufacturing of drug products that are sensitive to oxidation.


The potential laboratory health hazard of 210Pb and a simple procedure for separation of 210Pb from the daughters 210Bi and 210Po.
Lead 210 (Radium D) is a naturally occurring radionuclide which is frequently used in toxicological studies due to its long half-life. The use of 210Pb in tracer studies poses two problems. First, 210Pb, along with its daughters 210Bi and 210Po, presents a significant health hazard to laboratory personnel. Second, the presence of the daughter products may interfere with the detection of 210Pb, particularly by techniques which discriminate poorly between different radioactive emissions, e.g., autoradiography. The potential laboratory health hazards of 210Pb and its daughters are briefly reviewed and a simple dithiozone extraction procedure which allows quantitative separation of 210Pb frm the daughters 210Po and 210Bi is described. The purified 210Pb may then be utilized to reduce the health hazard from the daughter products and to construct calibration curves for the quantitation of 210Pb in the presence of 210Bi and 210Po by liquid scintillation counting.


[Protection of vascular endothelial cells from ox-LDL induced injury by protocatechualdehyde].
To observe the protective effects of protocatechualdehyde on the human umbilical vein endothelial cells (CRL-1730) induced injury by ox-LDL. The CRL-1730 were induced injury by ox-LDL, and then treated with protocatechualdehydes for 24 hours. The cytoactive of CRL-1730 was assessed by colorimetry of MTr, the NO level and NOS activity in the cell culture fluid were observed by colorimetry, and the expression of CD40 protein was determined by flow cytometry. Compared with the ox-LDL group, protocatechualdehyde increased,the number of CRL-1730 and the level of NO and NOS in cell culture fluid. Besides, protocatechualdehyde decreased the expression of CD40 protein, which was increased by ox-LDL. Protocatechualdehyde has protective effect on the CRL-1730 induced injury by ox-LDL and its mechanism of action may be related to the CD40/CD40L pathway.


Connectin, an elastic protein of muscle. A connectin-like protein from the plasmodium Physarum polycephalum.
A completely sodium dodecyl sulfate-insoluble protein was obtained from plasmodia of Physarum polycephalum. The amino acid composition of this protein was very similar to that of connectin, an elastic protein of muscle. When the protein suspension was treated with 6 M guanidine-HCl in the presence of 0.1 M 2-mercaptoethanol, entanglements of very thin filaments, less than 5 nm in width, were observed under an electron microscope. Since the network structure is almost the same as that of isolated muscle connectin, this plasmodium protein can be regarded as forming an elastic net structure. Using an antiserum against the insoluble protein, it appeared to be located at the peripheral region of the plasmodium. This elastic net structure may act as a cytoskeleton at the cytoplasmic surface of the plasmodium cell membrane.


Assessment of the susceptibility of Streptococcus pneumoniae to cefaclor and loracarbef in 13 countries.
Between July 1998 and July 1999, 2,644 clinical isolates of Streptococcus pneumoniae were collected from 27 study centers in 13 countries and their susceptibilities to penicillin, cefaclor and loracarbef were determined by E-test" (AB BIODISK, Solna, Sweden). Overall, 96.3% of isolates were penicillin-susceptible (79.8%) or -intermediate (16.6%) (MIC, < or = 1 microg/ml). Rates of penicillin-resistant S. pneumoniae isolation varied widely and were highest in the study centers tested in New Zealand (10.9%), Canada (10.0%), Mexico (9.1%) and the United States (5.1%). Low rates of penicillin-resistance were found in the study centers tested in Russia (0%), Turkey (0%), Brazil (0.5%), Germany (0.6%), Philippines (1.6%), Italy (2.1%), United Kingdom (2.3%), Australia (3.0%) and Poland (3.1%). Using recently published NCCLS interpretative breakpoints (M100-S10, 2000), 87.2% (median) of all isolates tested were cefaclor-susceptible and 87.8% (median) of all isolates tested were loracarbef-susceptible. Of the penicillin-susceptible S. pneumoniae isolates, 99.5% were susceptible to both cefaclor and loracarbef. Susceptibility to cefaclor and loracarbef was also retained by 30.8% and 32.9% of penicillin-intermediate isolates, respectively. These findings are in contrast to recent publications reporting lower cefaclor and loracarbef activities using non-validated interpretative criteria. In conclusion, rates of penicillin resistance among recent clinical isolates of pneumococci remain low in many centers worldwide. Cefaclor and loracarbef demonstrated excellent in vitro activity against recent clinical isolates of penicillin-susceptible and many isolates of penicillin-intermediate S. pneumoniae.


Pseudomonas fluorescens induces strain-dependent and strain-independent host plant responses in defense networks, primary metabolism, photosynthesis, and fitness.
Colonization of plants by nonpathogenic Pseudomonas fluorescens strains can confer enhanced defense capacity against a broad spectrum of pathogens. Few studies, however, have linked defense pathway regulation to primary metabolism and physiology. In this study, physiological data, metabolites, and transcript profiles are integrated to elucidate how molecular networks initiated at the root-microbe interface influence shoot metabolism and whole-plant performance. Experiments with Arabidopsis thaliana were performed using the newly identified P. fluorescens GM30 or P. fluorescens Pf-5 strains. Co-expression networks indicated that Pf-5 and GM30 induced a subnetwork specific to roots enriched for genes participating in RNA regulation, protein degradation, and hormonal metabolism. In contrast, only GM30 induced a subnetwork enriched for calcium signaling, sugar and nutrient signaling, and auxin metabolism, suggesting strain dependence in network architecture. In addition, one subnetwork present in shoots was enriched for genes in secondary metabolism, photosynthetic light reactions, and hormone metabolism. Metabolite analysis indicated that this network initiated changes in carbohydrate and amino acid metabolism. Consistent with this, we observed strain-specific responses in tryptophan and phenylalanine abundance. Both strains reduced host plant carbon gain and fitness, yet provided a clear fitness benefit when plants were challenged with the pathogen P. syringae DC3000.


Factors influencing infection rates after open fractures of the radius and/or ulna.
To investigate factors associated with the development of deep infection in patients with open fractures of the radius and/or ulna. We retrospectively reviewed 296 open fractures of the radius and/or ulna. Of these patients, 200 had at least 6-month follow-up and were included in this study. The following variables were examined for each patient: time from injury to antibiotic administration, time from injury to operative debridement, Gustilo-Anderson classification, type of antibiotic received, and host characteristics such as age, diabetes, and tobacco use. Outcome parameters included the presence of deep infection and fracture union. The overall rate of deep infection was 5% (10 of 200). No type 1 fractures (of 41) developed deep infection. In contrast, 4% (2 of 48) of type 2 and 7% (8 of 110) of type 3 fractures developed infection. Of 200 patients, 28 received antibiotics in less than 3 hours and underwent debridement in less than 6 hours from the time of injury; however, they did not have lower rates of infection. Similar findings were noted when nonunion was used as the outcome, and the association between Gustilo-Anderson classification and the development of nonunion was statistically significant. Factors such as time to antibiotics and time to operative debridement were not predictors for either rate of deep infection or nonunion in open fractures of the radius and/or ulna. The type of fracture as outlined by the Gustilo-Anderson classification was the factor most strongly associated with the development of deep infection and nonunion in these fractures. Therapeutic III.


The axonally secreted cell adhesion molecule, axonin-1. Primary structure, immunoglobulin-like and fibronectin-type-III-like domains and glycosyl-phosphatidylinositol anchorage.
Axonin-1 is an axon-associated cell adhesion molecule (AxCAM) of the chicken, which promotes neurite outgrowth by interaction with the AxCAM L1(G4) of the neuritic membrane. Here we report the cloning and sequence determination of a cDNA encoding axonin-1. Peptides generated by enzymatic cleavage showed similarity to the AxCAM F11. Degenerated polymerase chain reaction (PCR) primers were designed and an axonin-1 fragment was amplified from mRNA of embryonic retina. Screening of a cDNA library from embryonic brain resulted in the isolation of a 4.0-kb cDNA insert with an open reading frame of 3108 nucleotides. The deduced polypeptide of 1036 amino acids includes a putative hydrophobic N-terminal signal sequence of 23 or 25 amino acids and a C-terminal hydrophobic sequence of 29 amino acids which is suggestive of sequences serving as signal for the attachment of a glycosyl-phosphatidylinositol (glycosyl-PtdIns) anchor. The putative mature form of axonin-1 comprises six immunoglobulin-like repeats, followed by four fibronectin-type III repeats. Axonin-1 exhibits 75% amino acid identity with the AxCAM TAG-1 of the rat, suggesting that it is the chicken homologue of TAG-1. Like TAG-1, axonin-1 is glycosyl-PtdIns-anchored to the neuronal membrane; in contrast to TAG-1, it does not exhibit an Arg-Gly-Asp sequence.


Erectile dysfunction as a generalized vascular dysfunction.
We hypothesize that generalized vascular dysfunction may be the underlying cause in patients with erectile dysfunction (ED) without atherosclerosis and its major risk factors. In all, 30 outpatients with ED and 25 healthy volunteers as a control group were enrolled for this study. Aortic stiffness was calculated from data obtained by echocardiographic examination, which was performed using commercially available equipment with a 2.5- to 3.5-MHz transducer. Endothelium-dependent flow-mediated dilation (FMD) of the brachial artery was assessed using a high-resolution ultrasound system with a 10-MHz linear-array vascular transducer. Shear stress and nitroglycerin was used as a stimulus for assessing endothelium-dependent FMD and nonendothelium-dependent dilation of the brachial artery. FMD was significantly decreased in the ED group compared with control group (4.1 +/- 3.1% vs 9.7 +/- 3.5%, P < .001). Nonendothelium-dependent dilation was statistically insignificant in patients with ED compared with control subjects (13 +/- 3.9% vs 15.4 +/- 3.8%, P = .55). The relationship between ED and FMD was significant (r = -0.66, P < .001), whereas no relationship was found between ED and nonendothelium-dependent dilation (r = -0.23, P > .05). Aortic strain (3.7 +/- 2.7% vs 9.5 +/- 3.2%, P < .001) and distensibility (1.5 +/- 1.0 vs 4.7 +/- 2.9 cm2.dyne(-1).10(-3), P < .001) were found significantly lower in the ED group than in the control group. The relationship between ED and aortic stiffness was also significant (for aortic strain; r = -0.62, P < .001 and for aortic distensibility; r = -0.60, P < .001). Aortic and brachial artery functions are impaired in men with ED without cardiovascular disease or its major risk factors, indicating a more generalized vascular disease.


Poly (ADP-ribosyl)ation of RNA polymerase II from wheat germ.
Wheat germ RNA polymerase II is poly (ADP-ribosyl)ated in vitro by poly (ADP-ribose) synthetase purified from bovine thymus. RNA polymerase activity is decreased by 40% by the modification in conventional assays.


Alterations in auditory change detection associated with tinnitus residual inhibition induced by auditory electrical stimulation.
Residual inhibition (RI) is a temporary phenomenon that happens following offset of appropriate complete or partial acoustical and electrical masking stimulations in people who experience tinnitus. The biologic mechanisms associated with RI are not yet fully understood. Few studies have been focused on RI. Auditory mismatch negativity (MMN) as a change-detection tool may be an appropriate tool to explore the processing changes because of tinnitus and RI. The purpose of this study was to investigate alterations in auditory change detection and auditory sensory memory related to RI induced by auditory electrical stimulation (AES) using MMN brain mapping in participants with tinnitus. This investigation was a single-blind randomized controlled clinical trial study. Participants were randomly assigned into two groups: AES and placebo electrical stimulation (PES). Twenty-eight participants with chronic subjective tinnitus aged 22- to 45-yr-old participated in the study. After randomization, all participants received both AES and PES for 1 min in different sessions. Brain mapping of multifeature MMN paradigm was recorded from 29 scalp electrodes pre- and post-AES and PES. Following AES, participants were categorized into two groups: RI and nonresidual inhibition (NRI). The grand average MMN waveforms and isopotential topographic maps were obtained in RI, NRI, and PES groups. Three MMN parameters for five deviants of frequency, intensity, duration, location, and silent gap were compared among three groups of RI, NRI, and PES. Statistical analyses revealed significant between-subject effects for AES on MMN amplitude of frequency and duration deviant, MMN area under the curve of frequency, intensity, and duration deviants. Presence of RI can reestablish change-detection mechanisms in the central auditory pathways. It is suggested that MMN is reliable for assessment of change-detection system in people with tinnitus. It can be a useful technique in monitoring effects of treatments and rehabilitation.


Vitamin D in pediatric gastrointestinal disease.
The purpose of this review is to examine the prevalence of vitamin D deficiency in pediatric gastrointestinal disease, specifically celiac disease and inflammatory bowel disease (IBD); to discuss the role of vitamin D and its deficiency in gastrointestinal disease pathophysiology; and to present current literature regarding diagnosis and treatment of vitamin D deficiency in these pediatric gastrointestinal diseases. Vitamin D deficiency is common in children with gastrointestinal symptoms and disease processes. In celiac disease, vitamin D status should be routinely assessed at the time of diagnosis and during subsequent follow up if deficient. There is growing evidence to suggest an inverse association between vitamin D and IBD activity; however, the therapeutic role of vitamin D in IBD patients requires further investigation. Suboptimal vitamin D status commonly occurs in children with gastrointestinal disease. It is advisable to check serum 25-hydroxy vitamin D levels in children with newly diagnosed celiac disease and IBD. In celiac disease, vitamin D status should be assessed during subsequent follow up if deficient. In IBD, 25-hydroxy vitamin D levels should be checked at least yearly. Therapy should be provided to maintain a level of greater than 30 ng/ml but less than 100 ng/ml; however, the ideal vitamin D dosing regimen to treat vitamin D deficiency and to maintain this optimum level remains unknown. The role of vitamin D as a therapeutic agent in IBD is still under investigation.


Cloning and sequencing of curA encoding curvacin A, the bacteriocin produced by Lactobacillus curvatus LTH1174.
Curvacin A is a bacteriocin produced by Lactobacillus curvatus LTH1174 which is a potential starter organism for the production of fermented dry sausages. This peptide inhibits the growth of the opportunistic food pathogens Listeria monocytogenes and Enterococcus faecalis and thus, curvacin A may enable better performance of a starter and improvement of the hygienic status of meat products. Oligonucleotides were constructed deduced from the peptide sequence and used for the identification of the curvacin A structural gene curA on a 60 kb plasmid of L. curvatus LTH1174. Plasmid-cured derivatives of this strain were unable to produce curvacin A but were still resistant to the bacteriocin. CurA was cloned into Escherichia coli NM554 and its nucleotide sequence was determined. Sequencing revealed the presence of an additional open reading frame of 51 amino acids with unknown function. A promoter was detected upstream of curA by primer extension. Both reading frames form a single transcript. Curvacin A is synthesised as a prepeptide of 59 amino acids which is proteolytically processed to the mature bacteriocin of 41 amino acids.


Affective ambiguity for a group recruits ventromedial prefrontal cortex.
Affective appraisal often involves processing complex and ambiguous stimuli, such as the mood of a group people. However, affective neuroimaging research often uses individual faces as stimuli when exploring the neural circuitry involved in social appraisal. Results from studies using single face paradigms may not generalize to settings where multiple faces are simultaneously processed. The goal of the current study was to use a novel task that presents groups of affective faces to probe the medial prefrontal cortex (PFC), a region that is critically involved in appraisal of ambiguous affective stimuli, in healthy volunteers. In the current study, 27 subjects performed the Wall of Faces (WOF) task in which multiple matrices of faces were briefly presented during functional MRI. Subjects were asked to decide whether there were more angry or happy faces (emotional decision) or whether there were more male or female faces (gender decision). In each condition, the array contained either an equal (ambiguous trials) or an unequal (unambiguous trials) distribution of one affect or gender. Ambiguous trials relative to unambiguous trials activated regions implicated in conflict monitoring and cognitive control, including the dorsal anterior cingulate cortex (ACC), dorsolateral PFC, and posterior parietal cortex. When comparing ambiguous affective decisions with ambiguous gender decisions, the ventromedial PFC (including the ventral ACC) was significantly more active. This supports the dissociation of the ACC into dorsal cognitive and ventral affective divisions, and suggests that the ventromedial PFC may play a critical role in appraising affective tone in a complex display of multiple human faces.


PI3K in cancer-stroma interactions: bad in seed and ugly in soil.
Over the past decade the phosphoinositide-3 kinase (PI3K) signaling pathway emerged as an important player for tumor initiation and growth and, currently, PI3K inhibition constitutes a promising therapeutic approach for solid and hematological tumors. Beside its role in tumor cell evolution, PI3K signaling also provides integral functions for noncancerous cells that reside in healthy tissues surrounding the tumor, also referred as tumor microenvironment (TME). This review will address how PI3K signaling participates to the tumorigenic process and discuss the interaction between tumor cells and the surrounding TME, with particular focus on the role of PI3Ks in tumor-associated immune responses, tumor angiogenesis and metastasis formation.


Evaluation of immune responses in sheep induced by DNA immunization with genes encoding GRA1, GRA4, GRA6 and GRA7 antigens of Toxoplasma gondii.
The dense granule proteins of Toxoplasma gondii are investigated as possible vaccine candidates against the parasite. The aim of this research was to evaluate the immune responses of sheep injected twice, intramuscularly, with DNA plasmids encoding T. gondii dense granule antigens GRA1, GRA4, GRA6 and GRA7 formulated into liposomes. Control sheep were injected with an empty vector or received no injections. The injection of sheep with DNA plasmids encoding for GRA1, GRA4, GRA6 or GRA7 elicited an immune response after the first and the second injections as indicated by the moderate to high antibody responses. The injection of pGRA7 induced a significant level of anti-GRA7 IgG2 antibody and IFN-γ responses indicating a Th1-like immune response whereas injection with pGRA1, pGRA4 and pGRA6 stimulated a IgG1 type antibody response with a limited, if any, IFN-γ response. The results demonstrate that the intramuscular injection of sheep with a DNA liposome formulated plasmid coding for GRA proteins is an effective system that induces a significant immune response against T. gondii.


Differences in fat, carbohydrate, and protein metabolism between lean and obese subjects undergoing total starvation.
Despite extensive experimental studies on total starvation, many of the findings relating to protein, fat (plus ketone body), and carbohydrate metabolism remain confusing, although they become more consistent when considered in relation to the degree of initial obesity. During prolonged starvation, protein loss and percent energy derived from protein oxidation are 2- to 3-fold less in the obese than in the lean; percent urine N excreted as urea is 2-fold less in the obese; and the contribution of protein to net glucose production is only about half in the obese compared to lean subjects. During short-term starvation (first few days) the following differences are reported: hyperketonaemia is typically 2-fold greater in lean subjects, but associated with a 2-fold lower uptake of ketone bodies by forearm muscle; glucose tolerance becomes impaired more in lean subjects; and both protein turnover and leucine oxidation increase in the lean, but may show no significant change in the obese. It is no longer acceptable to describe the metabolic response to starvation as a single typical response. The differences between lean and obese subjects have important physiological implications, some of which are of obvious relevance to survival.


Necrotising soft-tissue infections of the upper limb: risk factors for amputation and death.
Necrotising soft-tissue infections (NSTIs) of the upper limb are uncommon, but potentially life-threatening. We used a national database to investigate the risk factors for amputation of the limb and death. We extracted data from the Japanese Diagnosis Procedure Combination database on 116 patients (79 men and 37 women) who had a NSTI of the upper extremity between 2007 and 2010. The overall in-hospital mortality was 15.5%. Univariate analysis of in-hospital mortality showed that the significant variables were age (p = 0.015), liver dysfunction (p = 0.005), renal dysfunction (P < 0.001), altered consciousness (p = 0.049), and sepsis (p = 0.021). Logistic regression analysis showed that the factors associated with death in hospital were age over 70 years (Odds Ratio (OR) 6.6; 95% confidence interval (CI) 1.5 to 28.2; p = 0.011) and renal dysfunction (OR 15.4; 95% CI 3.8 to 62.8; p < 0.001). Univariate analysis of limb amputation showed that the significant variables were diabetes (p = 0.017) mellitus and sepsis (p = 0.001). Multivariable logistic regression analysis showed that the factors related to limb amputation were sepsis (OR 1.8; 95% CI 1.5 to 24.0; p = 0.013) and diabetes mellitus (OR 1.6; 95% CI 1.1 to 21.1; p = 0.038). For NSTIs of the upper extremity, advanced age and renal dysfunction are both associated with a higher rate of in-hospital mortality. Sepsis and diabetes mellitus are both associated with a higher rate of amputation.