Evolution of Helicobacter pylori susceptibility to antibiotics during a 10-year period in Lithuania.
The study evaluated the changes in the prevalence of Helicobacter pylori strains with primary resistance to antibiotics during the last 10 years in Lithuania. H. pylori susceptibilities to antibiotics were tested in 89 patients in 1998, in 81 patients in 2001 and in 90 patients in 2007/2008. Susceptibility to metronidazole, clarithromycin, amoxicillin and tetracycline was tested using E-test or agar dilution method. Susceptibility to ciprofloxacin was only tested in 2007/2008. Data about utilization of all authorized and available on market macrolides and clindamycin in Lithuania during 2003-2007 were evaluated using WHO ATC/DDD methodology. A total of 260 H. pylori strains cultured from untreated adult patients were investigated. Primary resistance rates (1998, 2001 and 2007/2008) for metronidazole were 24.7%, 33.3%, and 35.6%, for clarithromycin 1.1%, 3.7%, and 3.3% and for tetracycline 0%, 2.5% and 0% respectively. No cases of amoxicillin resistance have been detected. The resistance rate for ciprofloxacin was 5.6% in 2007/2008. Data of total macrolides and clarithromycin utilization in Lithuania revealed that despite an increase of consumption of these drugs in Lithuania during 2003-2007 in 1.5 times, the total macrolide consumption remains one of the lowest in Europe. We have not observed any significant changes in the susceptibility of H. pylori to the most widely used antibiotics during the recent 10-year period. The low resistance rate to clarithromycin might be related to the policy to avoid use of macrolides as first-line treatment for pulmonary and other infections.


Biochemical and pharmacogenetic dissection of human steroid 5 alpha-reductase type II.
Human prostatic steroid 5alpha-reductase, encoded by the SRD5A2 gene on chromosome band 2p23, catalyses the irreversible conversion of testosterone to dihydrotestosterone (DHT), the most active androgen in the prostate, with NADPH as its cofactor. This enzyme has never been purified but a number of competitive inhibitors have been developed for this enzyme since increased steroid 5alpha-reductase activity may cause benign prostatic hypertrophy and prostate cancer. We report here the detailed biochemical and pharmacogenetic dissection of the human enzyme by analysing 10 missense substitutions and three double mutants which are all naturally found in humans. Nine of these 13 mutants reduce activity (measured as Vmax) by 20% or more, three increase steroid 5alpha-reductase by more than 15% and one results in essentially unaltered kinetic properties suggesting that it is a truly neutral ('polymorphic') amino acid substitution. Substantial pharmacogenetic variation among the mutants was also observed when three competitive inhibitors, finasteride, GG745 (dutasteride) and PNU157706, were investigated. Our studies not only define the substrate and cofactor binding sites of human steroid 5alpha-reductase, but also have significant consequences for the pharmacological usage of steroid 5alpha-reductase inhibitors in human patients treated for prostatic conditions.


[Cutaneo-viscero-hemolytic loxoscelism with acute renal failure].
The Loxoscelism is caused by the bite of spider Loxosceles laeta gender, of worldwide distribution. The poisoning can cause lesions dermonecrotic and less frequently a systemic illness that can be fatal. The mechanism of venom action is multifactorial. The characteristic dermonecrotic lesion results from the direct effects of the venom on the celular and basal membrane components, as well as the extracelular matrix. The initial interaction between the poison and tissues, causes complement activation, migration of polymorphic neutrophils, liberation of proteolytic enzymes, cytoquines, aggregation platelet, and blood flow alterations that result in edema and ischemia, with development of necrosis. There is no a definitive treatment for loxoscelism. However, the value of specific antivenom, to decrease lesion size and limit systemic illness even when such administration is delayed. We present a case of cutaneous-visceral loxoscelismo with unfavorable evolution.


[Periodontal diagnosis. Review of the literature].
The possible ways of diagnosis periodontal disease are examined in the light of what is reported in the literature. Particular stress is laid on the importance of the diagnosis of diseases "activity", a condition that is indispensable for the implementation of correct periodontal therapy.


Preparation of Multifunctional Liposomes as a Stable Vaccine Delivery-Adjuvant System by Procedure of Emulsification-Lyophilization.
Liposomes have been proven to be useful carriers for vaccine antigens and can be modified as a versatile vaccine adjuvant-delivery system (VADS). To fulfill efficiently both functions of adjuvant and delivery, the liposomes are often modified with different functional molecules, such as lipoidal immunopotentiators, APC (antigen-presenting cell) targeting ligands, steric stabilization polymers, and charged lipids. Also, to overcome the weakness of instability, vaccines are often lyophilized as a dry product. In this chapter the procedure of emulsification-lyophilization (PEL) is introduced as an efficient method for preparing a stable anhydrous precursor to the multifunctional liposomes which bear dual modifications with APC targeting molecule of the mannosylated cholesterol and the adjuvant material of monophosphoryl lipid A. The techniques and procedures for synthesis of APC targeting molecule, i.e., the mannosylated cholesterol, and for characterization of the multifunctional liposomes are also described.


Effects of losartan and amlodipine on intrarenal hemodynamics and TGF-beta(1) plasma levels in a crossover trial in renal transplant recipients.
Hypertension and hyperfiltration are two important risk factors for the development of chronic allograft nephropathy. Transforming growth factor-beta(1) (TGF-beta(1)) is the main cytokine involved in the fibrotic process that is involved in chronic rejection. Angiotensin II upregulates TGF-beta(1) production. Angiotensin II receptor antagonists therefore could not only control BP but also reduce TGF-beta(1) production in renal transplant patients. The aim of this study was to compare the effects of losartan and amlodipine on renal hemodynamics, as well as TGF-beta(1) and endothelin-1 (ET-1) plasma levels in a group of renal transplant patients who had normal renal function and who were treated with cyclosporine. Seventeen renal transplant patients who were receiving cyclosporine and who had normal graft function were included in a random 2 x 2 crossover trial with amlodipine and losartan (6 wk with each therapy). Three studies were performed (at baseline and at the end of both treatment periods) to determine renal hemodynamics, TGF-beta(1), and ET-1. Both treatments controlled BP to a similar degree, but only amlodipine increased GFR through an increase in the estimated glomerular hydrostatic pressure and filtration fraction. In contrast, losartan maintained GFR and reduced estimated glomerular hydrostatic pressure and filtration fraction significantly. Losartan and amlodipine had opposite effects on TGF-beta(1). Amlodipine did not affect TGF-beta(1) concentrations. In contrast, losartan reduced the plasma levels of TGF-beta(1) by approximately by 50% (from baseline, 5.2 to 2.6 ng/ml; P: = 0.01); the majority of the patients reached normal levels of TGF-beta(1). ET-1 concentrations were significantly higher during amlodipine compared with losartan treatment. The present study documents that with similar control of BP, losartan and amlodipine have opposite effects on renal hemodynamics and on TGF-beta1 concentrations. These differences could be important for the management of chronic allograft nephropathy.


Peripheral macro- and microcirculation in short-term insulin-dependent diabetes mellitus: the role of prostaglandins in early haemodynamic changes.
To determine whether vasodilator prostaglandins are involved in the peripheral hyperperfusion observed in patients with short-term insulin-dependent diabetes mellitus (IDDM), forearm and skin blood flow were studied before and after cyclooxygenase inhibition. Skin nutritive (CBV: capillary blood-cell velocity) and thermoregulatory (LDF: laser-Doppler fluxmetry), and forearm (muscle) blood flow (FBF) were measured before and after 500 mg acetylsalicylic acid (ASA) infused intravenously in 14 short-term IDDM patients and 22 healthy control subjects. In the IDDM patients, baseline LDF (median: 27 (19-35); interquartile range) vs. 17 (15-23) pu) and FBF (3.4 (2.5-4.1) vs. 2.6 (2.2-2.9) ml 100 ml-1 min-1) were increased, while CBV (0.70 (0.40-1.33) vs. 0.69 (0.41-0.96) mm s-1) was unchanged compared to healthy controls. ASA infusion had similar effects on baseline CBV, LDF, and FBF in patients and controls. In eight of the control subjects the role of prostaglandins in the regulation of basal peripheral blood flow was studied before and after ASA and placebo infusion. The changes in baseline CBV, LDF, and FBF were similar after ASA and placebo infusion in healthy controls. In conclusion, in short-term IDDM patients, increased skin thermoregulatory and forearm (muscle) blood flow are probably not related to vasodilator prostaglandins. Furthermore, prostaglandins are not likely to be involved in regulating basal peripheral blood flow in healthy man.


Comparison of virulence gene profiles of Escherichia coli isolates from sows with coliform mastitis and healthy sows.
Coliform mastitis (CM) is not only a serious economical and animal welfare touching problem in dairy cattle, but also in sows after farrowing. Due to this disease, the essential adequate supply with colostrum for the growth and the health of the piglets is not ensured. Besides other influencing factors, Escherichia (E.) coli is of great importance as a causative agent of this multifactorial disease. In this study, E. coli isolates from milk samples of healthy and CM-affected sows were examined for the presence of virulence genes associated with extraintestinal E. coli strains, enterotoxigenic E. coli and other pathogenic E. coli. The isolated E. coli harbored mainly virulence genes of extraintestinal E. coli strains (especially fimC, ompA, traT, hra, kpsMTII, iroN). The virulence gene spectrum for both samples from CM-affected and healthy sows did not differ significantly. Particular virulence gene profiles of E. coli isolates from diseased sows were not detected. This study provides novel insights into the role of E. coli in association with mastitis in sows since it is the first time E. coli isolates from CM-affected sows' milk were analysed for virulence genes. Because there were no differences in the prevalence of E. coli and their virulence-associated genes between healthy and diseased sows, other causative factors seem to have greater influence on the pathogenesis of porcine CM.


Oculomotor phenomena in petit-mal.
To determine the temporal relationship among behavior, eye movements and respiration during absence seizures. This included simultaneous videorecording of a patient's face, EEG and respirogram, in 5 patients with absence seizures. Absence seizures were defined as a sudden lapse of consciousness with impairment of mental functions. Oculomotor phenomena consisted of: eye fluttering, eye deviation (conjugate lateral or upward deflection), and eye-opening. Oculomotor phenomena began 1 2/3-3 s after the onset of the electrographic discharge and ended before the discharge. The most frequent events were eye-opening, stare with or without palpebral myoclonias, and tonic or clonic upward movements. Downward movement or convergence was not observed as well as head version. Respiratory changes (apnea) are the last events to occur. absence seizures were characterized by the onset of a 3/s spike-slow wave discharge followed by oculomotor phenomena and respiratory changes. The time course suggests that epileptic discharges precede and then involve oculomotor and respiratory brainstem centers.


Effect of pharmacist care on medication adherence and cardiovascular outcomes among patients post-acute coronary syndrome: A systematic review.
The impact of collaborative and multidisciplinary health care on the outcomes of care in patients with acute coronary syndromes (ACS) is well-established in the literature. However, there is lack of high quality evidence on the role of pharmacist care in this setting. This systematic review aimed to evaluate the impact of pharmacist care on patient outcomes (readmission, mortality, emergency visits, and medication adherence) in patients with ACS at or post-discharge. The following electronic databases and search engines were searched from their inception to September 2016: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science, Scopus, Campbell Library, Database of Abstracts of Reviews of Effects (DARE), Health System Evidence, Global Health Database, Joanna Briggs Institute Evidence-Based Practice Database, Academic Search Complete, ProQuest, PROSPERO, and Google Scholar. Studies were included if they evaluated the impact of pharmacist's care (compared with no pharmacist's care or usual care) on the outcomes of rehospitalization, mortality, and medication adherence in patients post-ACS discharge. Comparison of the outcomes with relevant statistics was summarized and reported. A total of 17 studies [13 randomized controlled trials (RCTs) and four non-randomized clinical studies] involving 8391 patients were included in the review. The studies were of variable quality (poor to good quality) or risk of bias (moderate to critical risk). The nature and intensity of pharmacist interventions varied among the studies including medication reconciliation, medication therapy management, discharge medication counseling, motivational interviewing, and post-discharge face-to-face or telephone follow-up. Pharmacist-delivered interventions significantly improved medication adherence in four out of 12 studies. However, these did not translate to significant improvements in the rates of readmissions, hospitalizations, emergency visits, and mortality among ACS patients. Pharmacist care of patients discharged after ACS admission was not associated with significant improvement in medication adherence or reductions in readmissions, emergency visits, and mortality. Future studies should use well-designed RCTs to assess the short- and long-terms effects of pharmacist interventions in ACS patients.


Cladribine decreases the level of angiogenic factors in patients with chronic lymphocytic leukemia.
We investigated the serum concentration of basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGFbeta1), using an enzyme linked immunosorbent assay (ELISA) in a group of 18 chronic lymphocytic leukemia (CLL) patients, before and after a successful treatment with cladribine (2-chlorodeoxyadenosine, 2-CdA) and 16 healthy volunteers. The serum level of bFGF was found to be significantly lower in the control group (median 0.15 pg/ml, range 0.0-15.7 pg/ml), when compared to the untreated CLL patients (median 41.4 pg/ml, range 2.1-292.6 pg/ml) (p=0.0002). After a successful 2-CdA treatment we observed a significantly lower level of this cytokine (median 10.55 pg/ml, range 0.4-140.4 pg/ml) (p=0.0019) in the same patients. However, the level of bFGF in this group was still higher than in the control group (p=0.003). The levels of TGFbeta1 were higher in the group of untreated CLL patients (median 31.36 ng/ml, range 14.36-75.71 ng/ml) than in the control group (median 28.35 ng/ml, range 10.85-70.10 ng/ml) (p=0.029). After the 2-CdA treatment serum concentration of this cytokine decreased significantly (median 20.34 ng/ml, range 3.02-43.85 ng/ml) (p=0.031) with similar levels present to that of the healthy control group (p=0.3). In conclusion, we have shown that the serum concentration of bFGF and TGFbeta1 in CLL patients were significantly reduced after 2-CdA chemotherapy that resulted in remission. The level of these factors might correlate with the activity of the disease.


Dissipation and residues of clethodim and its oxidation metabolites in a rape-field ecosystem using QuEChERS and liquid chromatography/tandem mass spectrometry.
A rapid, sensitive and selective method using Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) procedure for simultaneous determination of clethodim and its oxidation metabolites (clethodim sulfoxide and clethodim sulphone) in soil, rape plant and rape seed was developed using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The limits of detection (LODs) of the proposed method ranged from 0.002mg/kg to 0.01mg/kg, and average recoveries were 78.7-104.2%. The trial results showed that clethodim dissipated so rapidly that few clethodim residues were detectable. Clethodim sulfoxide dissipated quickly in rape plant and soil with half-lives of 4.3 and 4.0days, respectively. Clethodim sulphone showed a tendency of rapid increase initially followed by a decrease in rape plant but could not be detected in soil. The terminal residues of clethodim in rape seedsat harvest time were below the maximum residue limit (MRL, 0.5mg/kg).


Cholesterol enhances thrombin-induced release of fibroblast growth factor-2 in human vascular smooth muscle cells.
The mitogenic response to the G protein-coupled receptor agonist thrombin in human vascular smooth muscle cells (SMCs) depends on release of fibroblast growth factor-2 (FGF-2). Yet, intracellular mechanisms triggering FGF-2 release are unknown. The present study investigates possible effects of cholesterol enrichment and depletion, which have been shown to influence FGF-2-dependent signaling and SMC mitogenesis, on thrombin-induced FGF-2 release. Cultured human aortic and saphenous vein SMCs were enriched with cholesterol by using a cyclodextrin-cholesterol complex. Cholesterol accumulation was determined by a fluorometric assay. ELISA, Western blotting, and RT-PCR were used for quantification of FGF-2 levels. DNA synthesis was determined by [3H]-thymidine incorporation, proliferation by cell counting. Stimulation of SMCs with thrombin (30 nmol/L) resulted in release of FGF-2 into the pericellular space within 10 minutes. Preincubation with cyclodextrin-cholesterol caused accumulation of cellular cholesterol, increased thrombin-induced FGF-2 release, and stimulated FGF-2 de novo synthesis. Thrombin-induced DNA synthesis and proliferation were enhanced in cholesterol-rich SMCs. This effect was inhibited by FGF-2-neutralizing antibodies. Enhanced cellular cholesterol stimulates thrombin-induced release of FGF-2 and increases the mitogenic response toward thrombin in human SMCs. This mechanism might also be relevant for thrombin-induced mitogenesis in hypercholesterolemia in vivo.


Efficacy of viscous budesonide slurry for prevention of esophageal stricture formation after complete endoscopic mucosal resection of short-segment Barrett's neoplasia.
Complete endoscopic resection (CER) of short-segment Barrett's esophagus with high grade dysplasia (HGD) and early esophageal adenocarcinoma (EEA) is a precise staging tool and achieves durable disease control. The major drawback is development of post-endoscopic resection esophageal stricture (PERES). No effective therapy to prevent PERES has been described. Viscous budesonide slurry (VBS) may have a role in the prevention of PERES by suppressing the post-CER inflammatory process. The study aim was to evaluate the efficacy of VBS for the prevention of PERES. Prospective data were collected on patients referred for CER of HGD or EEA. After January 2012, patients routinely received VBS (two 0.5-mg/2-mL budesonide respules mixed with sucralose) twice daily for 6 weeks following each stage of the CER schedule. All patients received high dose proton pump inhibitor therapy for the duration of CER and the following 3 months. Patients had no other intervention to prevent PERES. A validated dysphagia score was used (0 - 4, no dysphagia to aphagia). Endoscopic dilation was performed for dysphagia. Patients receiving VBS were compared with historical controls. The primary endpoint was the need for dilation. Between January 2008 and January 2015, 104 of 116 eligible patients completed CER. The VBS group (n = 29) and non-VBS group (n = 75) had similar patient, disease, and procedural characteristics. Dilations were needed in 13.8 % vs. 37.3 % (P = 0.03), with a median of one vs. two procedures (P = 0.01), and median dysphagia score during CER of 0 vs. 1 (P = 0.02) in the VBS and non-VBS groups, respectively. No VBS-related adverse events were noted. In this pilot study VBS significantly reduced PERES and shortened the dilation program after CER.


Molecular biology of channelopathies: impact on diagnosis and treatment.
Channelopathies are genetically determined ion channel alterations that lead to acute and transient symptoms in subjects who otherwise appear to be normal. This article reviews the recent progression of biomolecular studies that have clarified the mechanisms by which gene mutations may result in alterations of excitable tissues responsible for episodic neurological, neuromuscular and cardiac disorders, defined as channelopathies. The development of technologies capable of testing pharmacological agents in vitro on mutated channels expressed in cell lines makes it possible to define a more rational use of the available drugs acting on ion channels, and to design new molecules specifically targeted to known channel dysfunctions and new ones that could be identified by future genetic studies.


Comparison of Alzheimer's disease in Native Americans and Whites.
This study compared medical history and findings on initial clinical examination in Native Americans diagnosed with possible or probable Alzheimer's disease (AD) at Native American satellite clinics of the University of Texas (UT) Southwestern Medical Center's Alzheimer's Disease Center with those of Whites diagnosed with probable AD at the UT Southwestern Medical Center's Alzheimer's Disease Clinic. The information reviewed was contained in the database of the UT Southwestern Alzheimer's Disease Center. In relation to Whites, Native Americans had slightly but significantly greater age at onset of symptoms (71.7 vs. 69.6 years, t = -2.08, p = .04) and equivalent cognitive scores at evaluation (Mini-Mental State Exam score = 17.4 vs. 18.5, t = 0.98, p = .33), despite significantly lower educational level (11.4 vs. 13.4 years, t = 5.63, p < .001). Native Americans were more frequently depressed on examination (22.8% vs. 9.5%, chi2 = 12, p = .001) and reported diabetes, hypertension, and heart disease significantly more often than did Whites (p < .01 for all), but their survival time after AD diagnosis was similar to that of Whites despite these comorbidities. With the exception of a greater prevalence of depression and cardiovascular risk factors in Native Americans than in Whites, Native Americans had a course of illness similar to that of Whites.


Long-term results of laryngotracheal resection for benign stenosis from a series of 109 consecutive patients.
Long-term results of patients undergoing laryngotracheal resection for benign stenosis are reported. This is the largest series ever published. Between 1991 and March 2015, 109 consecutive patients (64 males, 45 females; mean age 39 ± 10.9 years) underwent laryngotracheal resection for subglottic postintubation (93) or idiopathic (16) stenosis. Preoperative procedures included tracheostomy in 35 patients, laser in 17 and laser plus stenting in 18. The upper limit of the stenosis ranged between actual involvement of the vocal cords and 1.5 cm from the glottis. Airway resection length ranged between 1.5 and 6 cm (mean 3.4 ± 0.8 cm) and it was over 4.5 cm in 14 patients. Laryngotracheal release was performed in 9 patients (suprahyoid in 7, pericardial in 1 and suprahyoid + pericardial in 1). There was no perioperative mortality. Ninety-nine patients (90.8%) had excellent or good early results. Ten patients (9.2%) experienced complications including restenosis in 8, dehiscence in 1 and glottic oedema requiring tracheostomy in 1. Restenosis was treated in all 8 patients with endoscopic procedures (5 laser, 2 laser + stent, 1 mechanical dilatation). The patient with anastomotic dehiscence required temporary tracheostomy closed after 1 year with no sequelae. One patient presenting postoperative glottic oedema underwent permanent tracheostomy. Minor complications occurred in 4 patients (3 wound infections, 1 atrial fibrillation). Definitive excellent or good results were achieved in 94.5% of patients. Twenty-eight post-coma patients with neuropsychiatric disorders showed no increased complication and failure rate. Laryngotracheal resection is the definitive curative treatment for subglottic stenosis allowing very high success rate at long term. Early complications can be managed by endoscopic procedures achieving excellent and stable results over time.


Megakaryocyte DNA content and platelet formation in rats after a sublethal dose of thio-TEPA.
The megakaryocytopoiesis in rats was studied following a single dose of thio-TEPA to determine the mechanisms for the thrombocytopenia and subsequent recovery. The blood platelet number, platelet production (measured by 35S incorporation into platelets), mean platelet volume, and the number and DNA content of bone marrow megakaryocytes (MK) were observed. The blood platelet counts, platelet production, and total MK number decreased to low values following the administration of thio-TEPA, and stayed low until regeneration started around day 10. The mean platelet volume increased from the normal 6.6 fl to 7.8 fl during the early regeneration days 8-14. The MK were divided into four ploidy classes: 2N-4N, 8N, 16N, and 32N-64N. The number of MK within all ploidy classes decreased to nearly zero within four days after the injection of thio-TEPA. The regeneration started around day 10 with increasing numbers of 2N-4N and 8N MK, while the number of 16N and 32N-64N MK increased more than four days later. It is concluded that decreased or blocked influx of progenitor cells into the MK compartment is the main reason for thrombocytopenia after exposure to thio-TEPA.


Loss of beta1 integrin function results in a retardation of myogenic, but an acceleration of neuronal, differentiation of embryonic stem cells in vitro.
Integrin cell surface receptors play an important role for cell adhesion, migration, and differentiation during embryonic development by mediating cell-cell and cell-matrix interactions. Less is known about the function of integrins during commitment and lineage determination of early embryogenesis. Homozygous inactivation of the beta1 integrin gene results in embryonal death in mice around the time of implantation. In vitro, differentiation of embryonic stem (ES) cells which lack beta1 integrin (beta1-/-) into the cardiogenic lineage is delayed and results in a disordered cellular specification (Fässler et al., J. Cell Sci. 109, 2989-2999, 1996). To analyze beta1 integrin function during myogenesis and neurogenesis we studied differentiation of beta1-/- ES cells via embryoid bodies into skeletal muscle and neuronal cells in vitro. beta1-/- cells showed delayed and reduced myogenic differentiation compared to wildtype and heterozygous (beta1+/-) ES cells. RT-PCR analysis demonstrated delayed expression of skeletal muscle-specific genes in the absence of beta1 integrin. Immunofluorescence studies with antibodies against the sarcomeric proteins myosin heavy chain, titin, nebulin, and slow C-protein showed that myotubes formed, but their number was reduced and the assembly of sarcomeric structures was retarded. In contrast, neuronal cells differentiating from beta1-/- ES cells appeared earlier than wildtype and heterozygous (beta1+/-) ES cells. This was shown by the accelerated expression of neuron-specific genes and an increased number of neuronal cells in beta1-/- embryoid bodies. However, neuronal outgrowth was retarded in the absence of beta1 integrin. No functional difference between wildtype and beta1-/- cells was found with respect to secretion of gamma-aminobutyric acid, the main neurotransmitter of ES cell-derived neuronal cells. The lineage-specific effects of loss of beta1 integrin function, that is the inhibition of mesodermal and acceleration of neuroectodermal differentiation, were supported by differential expression of genes encoding lineage-specific transcription factors (Brachyury, Pax-6, Mash1) and signaling molecules (BMP-4 and Wnt-1). Because of the reduced and delayed expression of the BMP-4 encoding gene in beta1-/- cells, we analyzed in wildtype and beta1-/- cells the regulatory role of exogenously added BMP-4 on the expression of the mesodermal and neuronal marker genes, Brachyury and wnt-1, respectively. The data suggest that BMP-4 plays a regulatory role during differentiation of wildtype and beta1-/- cells by modifying mesodermal and neuronal pathways. The reduced expression of BMP-4 in beta1-/- cells may account for the accelerated neuronal differentiation in beta1-/- ES cells.


[Stress].
Any change in the social or physical environment that threatens the needs or interests of a mammal, induces a state of tension ('stress') in the animal. Driven by this tension, the animal changes its behaviour. At the same time, alterations occur in bodily functions. All organs and regulatory systems (central and peripheral nervous systems, endocrine and immune systems) participate in these behaviour-physiological response and are affected in their activities. The character of the reactions (e.g. fight, flight, passivity) is mainly determined by the animals appraisal of the environmental change and of the possible impact of its response. Aim of the reactions is neutralising the threat and gaining control over the environment (adaptation). When this is achieved, the tension recedes. In case the response is unsuccessful, the state of tension persists ('chronic stress'). Prolonged exposure of brain and/or bodily functions to stress can result in pathological states.


Mosaic evolution of prepropancreatic polypeptide. II. Structural conservation and divergence in pancreatic polypeptide gene.
We demonstrated that nucleotide and amino acid sequences in the carboxyl-terminal regions of rat, mouse, and human prepropancreatic polypeptide exhibit a high degree of divergence, whereas the amino-terminal domains are highly conserved. To understand the molecular basis of this divergence and conservation, we determined the nucleotide sequence of the rat pancreatic polypeptide gene from an islet genomic library and compared it with that of the human gene. Exon 2 of the rat gene encodes the signal peptide and pancreatic polypeptide, exon 3 encodes the carboxyl-terminal region, and exons 1 and 4 encode the 5'- and 3'- untranslated regions of the mRNA, respectively. Exons 1 and 2 of rat and human genes are well conserved. The rat and human genes, however, have exons 3 and 4 of different lengths and heterologous nucleotide sequences. Mutational accumulation in exons 3 and 4 and intron 3 of the rat gene appears to have caused splice junction sliding and translational frameshift, resulting in a structural divergence in the carboxyl-terminal region. Available evidence indicates that the mosaicism of structural conservation and divergence in pancreatic polypeptide genes may have been caused by a difference in the evolutionary rates of the genomic regions.


Assay of reducing end-groups in oligosaccharide homologues with 2,2'-bicinchoninate.
For the first time, reducing values of homologous series of oligosaccharides have been determined by the 2,2'-bicinchoninate assay. The extent of Cu2+ reduction was monitored by spectrophotometric measurement of Cu+/2,2'-bicinchoninate complexes. Conditions of the assay were optimized so that relatively uniform reducing values were obtained with oligosaccharides derived from starch, polygalacturonic acid, and chitin, regardless of degree of polymerization. The uniform values resulted because members of each oligosaccharide series were oxidized to similar levels beyond the aldonic acid stage, while oxidation was limited to the reducing-terminal residue. This conclusion was based on direct measurements of quantitative loss of paramagnetic copper (Cu2+) by electron paramagnetic resonance spectroscopy.


Opioid-prescribing Outcomes of Medicare Beneficiaries Managed by Nurse Practitioners and Physicians.
Primary care providers are at the center of the opioid epidemic. Whether nurse practitioners (NPs) have different opioid-prescribing outcomes from physicians is not known. To examine opioid-prescribing outcomes of Medicare beneficiaries receiving care from NPs and physicians in primary care. We used Medicare data from 2009 to 2013 and a propensity score-weighted analysis. Beneficiaries residing in states in which NPs are able to prescribe controlled substances without physician oversight and who did not have a cancer diagnosis, hospice care, or end-stage renal disease. First, we measured whether beneficiaries received any opioid prescription. Second, for beneficiaries who received opioids, we measured acute (<90 d supply) and chronic (≥90 d supply) use at baseline (2009-2010) and follow-up (2012-2013). Third, we measured potential misuse of opioid prescribing using a daily morphine milligram equivalent dose of >100 mg, overlapping prescriptions of opioids >7 days, and overlapping prescriptions of opioids with benzodiazepines >7 days. Beneficiaries managed by NPs were less likely to receive an opioid [odds ratio (OR), 0.87; P<0.001], were less likely to be acute users at baseline (OR, 0.84; P<0.001), and were more likely to receive a high daily opioid dose of morphine milligram equivalent >100 mg compared with physician-managed beneficiaries (OR, 1.11; P=0.048). Findings suggest educational programs and clinical guidelines may require approaches tailored to different providers. Future research should examine the contributing factors of these patterns to ensure high-quality pain management and guide policy makers on NP-controlled substance-prescribing regulations.


A Meta-Analysis of Risk and Protective Factors for Dating Violence Victimization: The Role of Family and Peer Interpersonal Context.
Dating violence (DV) is a widespread social issue that has numerous deleterious repercussions on youths' health. Family and peer risk factors for DV have been widely studied, but with inconsistent methodologies, which complicates global comprehension of the phenomenon. Protective factors, although understudied, constitutes a promising line of research for prevention. To date, there is no comprehensive quantitative review attempting to summarize knowledge on both family and peer factors that increase or decrease the risk for adolescents and emerging adults DV victimization. The current meta-analysis draws on 87 studies with a total sample of 278,712 adolescents and young adults to examine effect sizes of the association between various family and peer correlates of DV victimization. Results suggest small, significant effect sizes for all the family (various forms of child maltreatment, parental support, and parental monitoring) and peer factors (peer victimization, sexual harassment, affiliation with deviant peers, and supportive/prosocial peers) in the prediction of DV. With few exceptions, forms of DV (psychological, physical, and sexual), gender, and age did not moderate the strength of these associations. In addition, no difference was found between the magnitude of family and peer factors' effect sizes, suggesting that these determinants are equally important in predicting DV. The current results provide future directions for examining relations between risk and protective factors for DV and indicate that both peers and family should be part of the development of efficient prevention options.


Helicobacter pylori induces proinflammatory cytokines and major histocompatibility complex class II antigen in mouse gastric epithelial cells.
Although Helicobacter pylori has been reported to stimulate the release of various cytokines from gastric tissue, it remains unknown whether normal and nontumorous gastric epithelial cells produce these cytokines. Therefore, in this study, we used a normal mouse gastric surface mucous cell line (GSM06) to determine whether gastric epithelial cells produce proinflammatory cytokines in response to H. pylori. The expression of MHC class II antigen was also examined, to investigate whether gastric epithelial cells participate in the immune response to H. pylori. In the study, GSM06 cells were incubated with H. pylori or its lipopolysaccharide (LPS). Proinflammatory cytokines were detected by Northern and Western blot analysis. The expression of MHC class II antigen was examined by fluorescence activated cell sorter (FACS) analysis. Genetic expression of proinflammatory cytokines such as interleukin-1alpha, tumor necrosis factor-alpha, and cytokine-induced neutrophil chemoattractant-2beta was enhanced by both intact and sonicated H. pylori, but not by H. pylori LPS. The expression of MHC class II antigen was induced by H. pylori more strongly than by interferon-gamma. We conclude that H. pylori induces the expression of proinflammatory cytokines and MHC class II antigen in gastric epithelial cells. Gastric epithelial cells may act as antigen-presenting cells and participate in the immune response to H. pylori infection.


Intrinsic properties of reverse transcriptase in reverse transcription. Associated RNase H is essentially regarded as an endonuclease.
The intrinsic properties of reverse transcriptase in reverse transcription were studied using a synthetic, partial ovalbumin mRNA with a synthetic DNA oligonucleotide annealed to the 3'-end of the RNA as a model substrate. With or without concomitant cDNA synthesis, the RNase H activity of avian myeloblastosis virus (AMV)-reverse transcriptase cleaved the substrate at a site which would leave a hybrid of between 7 and 14 base pairs between the 3' termini of the RNA and DNA oligonucleotide. Variability in the exact size of the hybrid probably reflects some weak base preference for cleavage by the enzyme. These short hybrids can be recognized as substrates by Escherichia coli RNase H and can be utilized by reverse transcriptase as sites for continuation of cDNA synthesis. Substrates with 5'-triphosphorylated termini, 3'-OH, 3'-phosphate, 3'-end hairpin structures and 20 base pair hybrids on the middle region of long RNA more than 300 bases or on circular RNA were all cleaved by AMV-reverse transcriptase-associated RNase H, indicating that the RNase H activity is essentially regarded as an endonuclease degrading RNA moiety in RNA-DNA hybrid. The modes of action of reverse transcriptase from murine leukemia virus and Rous-associated virus 2 were the same as that of AMV-reverse transcriptase, except that the size of the remaining hybrid and the specificity for cleavage depended on the reverse transcriptase. We propose a possible model to explain the mode of action of RNase H and RNA-dependent DNA polymerase activities in reverse transcription.


Analysis of the GAP-related domain of the neurofibromatosis type 1 (NF1) gene in childhood brain tumors.
The neurofibromatosis type-1 (NF1) gene contains a 360-bp region with significant homology to the catalytic domain of mammalian GTPase-activating protein. This particular GAP-related domain of the NF1 gene (NF1-GRD) stimulates ras GTPase and inactivates ras protein p21ras. Therefore, it has been suggested that the NF1 gene represents another tumor-suppressor gene. In the search for molecular markers of possible diagnostic relevance, childhood brain-tumor specimens of different histologic diagnoses were tested for mutations of the so-called FLR-exon within the NF1-GRD. This part of the NF1-GRD has been shown to be most crucial for the GAP-like function. Using a highly sensitive PCR-SSCP technique, we tested 51 tumor specimens were tested, but found no mutations. We conclude that inactivation of this putative tumor-suppressor gene by mutations does not play a significant role in tumorigenesis of childhood brain tumors. Next, we compared the splice variants of the NF1-GRD in 33 brain tumors and 8 extraneural embryonal tumors. Primitive neuroectodermal tumors (PNET) (n = 10) and one intracranial teratoma were the only tumors that predominantly expressed a splice pattern that can be observed in the immature developing brain. In contrast to other embryonal neuronal tumors, this NF1-GRD splicing pattern could not be modified in a newly established medulloblastoma cell line by retinoic acid treatment. Since this particular splice variant suppresses p21ras more effectively than other NF1-GRD transcripts, its predominant expression may interfere with the physiological signal transduction of p21ras during differentiation of neurons. There may be a neurofibromin-induced and p21ras-mediated differentiation pathway of neuronal stem cells that is blocked in PNET. Such an arrest of a p21ras-dependent differentiation pathway may explain the persistence of primitive pluripotent neuronal cells in PNET.


Pretransplant cachexia and morbid obesity are predictors of increased mortality after heart transplantation.
Extremes in body weight are a relative contraindication to cardiac transplantation. We retrospectively reviewed 474 consecutive adult patients (377 male, 97 female, mean age 50.3+/-12.2 years), who received 444 primary and 30 heart retransplants between January of 1992 and January of 1999. Of these, 68 cachectic (body mass index [BMI]<20 kg/m2), 113 overweight (BMI=>27-30 kg/m2), and 55 morbidly obese (BMI>30 kg/m2) patients were compared with 238 normal-weight recipients (BMI=20-27 kg/m2). We evaluated the influence of pretransplant BMI on morbidity and mortality after cardiac transplantation. Kaplan-Meier survival distribution and Cox proportional hazards model were used for statistical analyses. Morbidly obese as well as cachectic recipients demonstrated nearly twice the 5-year mortality of normal-weight or overweight recipients (53% vs. 27%, respectively, P=0.001). An increase in mortality was seen at 30 days for morbidly obese and cachectic recipients (12.7% and 17.7%, respectively) versus a 30-day mortality rate of 7.6% in normal-weight recipients. Morbidly obese recipients experienced a shorter time to high-grade acute rejection (P=0.004) as well as an increased annual high-grade rejection frequency when compared with normal-weight recipients (P=0.001). By multivariable analysis, the incidence of transplant-related coronary artery disease (TCAD) was not increased in morbidly obese patients but cachectic patients had a significantly lower incidence of TCAD (P=0.05). Cachectic patients receiving oversized donor hearts had a significantly higher postoperative mortality (P=0.02). The risks of cardiac transplantation are increased in both morbidly obese and cachectic patients compared with normal-weight recipients. However, the results of cardiac transplantation in overweight patients is comparable to that in normal-weight patients. Recipient size should be kept in mind while selecting patients and the use of oversized donors in cachectic recipients should be avoided.


[Influence of Different Ablation Frequencies on the Clinical Results of Photorefractive Keratectomy Using the Same Excimer Laser Platform: A Contralateral Eye Study].
Background The objective of this study was to evaluate postoperative clinical outcomes of photorefractive keratectomy (PRK) using different ablation frequencies. Patients and Methods In this prospective, contralateral eye study, 56 eyes of 28 patients with myopia or myopic astigmatism were included. PRK was performed using the MEL90 excimer laser system (Carl Zeiss Meditec, Germany). One eye of each patient was treated with a repetition rate of 250 Hz, while the other one was treated with a repetition rate of 500 Hz. The treatment pattern in the 250 Hz and 500 Hz group only differed in terms of ablation frequency; there was no difference in laser pulse energy, spot size or ablation profile. Postoperative follow-ups were at 3 and 7 days and 1, 3 and 6 months. The following parameters were assessed: Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), higher-order aberrations (HOAs), corneal re-epithelisation time and corneal haze. Results Ablation depth was proportional to laser pulse counts at both frequencies. At 6 months, 100.0% of the eyes in the 250 Hz group and 96.4% in the 500 Hz group had a UDVA of 0.00 logMAR or better; 100% of the eyes in both groups were within ± 1.00D of the attempted correction. All eyes had a postoperative CDVA of 0.00 logMAR or better. There was no difference between the groups in postoperative HOAs, corneal re-epithelisation time or corneal haze. Conclusions Photorefractive keratectomy with a repetition rate of 250 Hz and 500 Hz showed comparable efficacy, safety and predictability in the correction of myopia. There were no significant complications due to the high repetition rate, such as postsurgical corneal haze.


Discharge patterns of hypoglossal motoneurons during fictive breathing, coughing, and swallowing.
We performed a series of experiments to study the intracellular activity of 58 hypoglossal motoneurons (HMs) in decerebrate, paralyzed, and ventilated cats. Changes in membrane potentials (MP) and discharge activities were evaluated during fictive breathing (FB), swallowing (FS), and coughing (FC). FS and FC were elicited by electrical stimulation of the superior laryngeal nerves. FB, FS, and FC all exhibited characteristic discharge patterns of the phrenic, abdominal, pharyngeal branch of the vagus, and hypoglossal nerves. Thirty-nine HMs displayed respiratory modulation, and 19 were nonrespiratory modulated. Nine HMs did not exhibit MP changes during FB, FS, and FC. During FS, 49 HMs exhibited MP changes consisting of depolarization, hyperpolarization or hyperpolarization-depolarization. HMs involved in FS were either respiratory modulated (n = 38) or not (n = 11). Only 20 HMs displayed MP changes and/or discharge activity during FC. All but two HMs fired during the expiratory phase of FC or at the end of this reflex. All HMs involved in FC (n = 20) were also modulated during both FB and FS. Our results suggest that the XII nucleus is functionally divided into common and distinct subsets of HMs based on their spontaneous activities and responses observed during FS and FC. The changes in MP and discharge frequencies observed during the three behaviors also suggest that HMs are driven by specific premotor neurons during FS, whereas a common premotor pathway is involved during FB and FC.


Does intensive outpatient cocaine treatment reduce AIDS risky behaviors?
The purposes of this study were: (1) to examine the characteristics of 447 cocaine dependent, first admission outpatients in relation to their AIDS risky behavior at intake; (2) to ascertain whether there was a reduction in risky behavior at follow-up 9 months after admission; and (3) to determine whether reductions in risky behavior were related to patient characteristics, group as compared to individual treatment, or time in treatment. In this sample of cocaine dependent patients entering outpatient treatment, those engaging in higher AIDS risky behaviors were not characterized by any particular demographic profile or by a lack of knowledge about HIV/AIDS. They did have higher scores on the SCL-90-R symptom scales, the Beck Depression Inventory, and higher ratings on the Drug, Alcohol, Family, and Medical scales of the ASI. At 9-month follow-up, AIDS risky behaviors as measured by the RAB were found to have decreased significantly. The degree of improvement was not associated with demographic variables but was predicted by higher intake problem severity and psychological symptomatology scale scores. While improvement in risky behavior was not related to type of treatment or duration of treatment, it was related to decreased substance use. The individuals whose risky behavior decreased were those whose substance use had decreased. Improvement, then required not only being in a treatment program, but also participation and involvement in the program. Treatment and not merely attendance would seem to be critical.


Intensity-independent fluorometric detection of cellular nitric oxide release.
A new fluorescence method is introduced in which nitric oxide (NO)-derived higher-order oxygen complexes (NO(x)) are quantified at physiological pH. Detecting the fluorescence lifetime shift between 2,3-diaminonaphthalene and the NO(x)-derived protonated 2,3-naphthotriazole allows an intensity independent determination of the NO(x) concentration. The NO release from LPS and IFNgamma-stimulated murine macrophages and iNOS transfected hamster cells was quantified. The lower detection limit for NO2- was found to be 800 pmol/ml. Since the influence of static fluorescence quenching due to cellular components can be neglected, the method is applicable for clear cellular supernatants as well as turbid cellular suspensions.


Peroxidase-linked assay for detection of antibodies against bovine leukosis virus.
A peroxidase linked assay (PLA) was designed to screen bovine sera for the presence of specific antibodies against bovine leukosis virus (BLV). Out of 201 samples of bovine sera analyzed, 52.2% were considered positive by PLA, 26.4% by AGID, and 38.9% by ELISA. Western blotting analyses excluded 27 samples found to be positive by PLA. PLA showed 100% of sensitivity when compared with AGID and ELISA. Specificity was 64.8% and 78%, respectively (kappa coefficients were 0.70 and 0.83). These findings indicate that PLA can be used as an alternative method for the diagnosis of BLV infection in cattle.


The changes in residual cancer burden after interval debulking surgery are effective in evaluating the response to adjuvant chemotherapy.
To study the clinical significance of the change of residual cancer burden (RCB) of epithelial ovarian carcinoma (EOC) between primary (PDS) and interval debulking surgery (IDS) in order to evaluate the effectiveness of adjuvant chemotherapy. Thirty-eight EOC patients with suboptimal PDS with adjuvant chemotherapy were selected for this retrospective study and divided into pathologically negative (group A) and pathologically positive (group B) groups based on the histopathological examination and the change of size of residual disease after IDS. Patients in group B were further divided into groups B1 (partial remission criteria, n = 9), B2 (consistent with stable disease, n = 12) and B3 (consistent with disease progression, n = 4) based on the changes in RCB between PDS and IDS and the guidelines to evaluate the response to treatment in solid tumors (Response Evaluation Criteria in Solid Tumors, RECIST). The responses to chemotherapy evaluated by pathological examination of RCB versus by CA-125, recurrence patterns, and prognoses were analyzed. The clinical benefit rates evaluated by pathological assessment for groups A, B1, B2 and B3 were 100, 100, 100 and 0%, respectively (p < 0.01), whereas the rates were not statistically different when evaluated by CA-125 (100, 100, 91.7 and 100%, respectively; p > 0.05). The median progression-free survival (PFS) for patients in groups A and B was 36 and 6 months, respectively (p < 0.05); the median overall survival (OS) was 93 and 42 months, respectively (p < 0.05). There were no significant differences in median PFS or OS among patients in groups B1, B2 and B3 (PFS: 16, 6 and 1.5 months; OS: 52, 31 and 30.5 months, respectively; all p > 0.05), but there were significant differences in median PFS or OS between B1 and B3. There was no significant difference in recurrence rates between groups A and B (53.8 vs. 72.0%, p > 0.05), but there were significant differences in the rate of drug-resistant recurrence [28.6% (2/7) vs. 72.2% (13/18), p < 0.05] and in median PFS of relapsed patients (19 vs. 4 months, p < 0.05). The histopathological assessment of RCB between PDS and IDS may be used to evaluate and predict the response to adjuvant chemotherapy in EOC.


Rectal duplications.
Recent experience with two cases of rectal duplication, which had been misdiagnosed as hemorrhoids, or fistula-in-ano with resultant delay in diagnosis, prompted us to review our prior experience with 11 of these unusual cases. Age at presentation ranged from newborn to 18 years (mean, 17 months). The most common presenting sign was a perianal or anal fistula, observed in five children. Two children presenting with fistulae had concomitant infection in the duplication. Other presenting signs included obstruction or prolapse caused by the rectal mass in three patients, rectal bleeding in three, and urinary retention in one. Some children presented with more than one finding. No associated spinal or vertebral anomalies were observed. Total excision was performed using a transanal approach in eight patients, postanal (transcoccygeal) in two, and posterior sagittal in one. Postoperative continence was normal in all patients. These cases illustrate that rectal duplications can be confused with other types of anorectal pathology including hemorrhoids, fistula-in-ano, and perirectal abscess. Total excision performed using a posterior sagittal, transanal, or transcoccygeal approach is curative.


Spinal leptomeningeal metastases following glioblastoma multiforme treated with radiotherapy.
A case of glioblastoma with leptomeningeal spread after control of the primary lesion by radiation therapy. A discussion is made regarding leptomeningeal metastatic disease with reference to the literature.


Microfilament bundles in antheridial nuclei of Achlya ambisexualis E 87.
This is the first report of intranuclear microfilaments within gametangial nuclei of oömycetous fungi. Longitudinal sections of four to six microfilaments were frequently observed in meiotic antheridial nuclei of Achlya ambisexualis. Each microfilament measured approximately 7--10 nm in diameter. Spindle tubules (25 nm in diameter) were also observed within some of the nuclei possessing microfilaments.


MO-A-213AB-05: Synthesis of High Quantum Yield Nano-Scintillators for Simultaneous Photodynamic Therapy in Radiotherapy.
Radioresistant tumors provide one of the biggest challenges for improving radiation therapy efficacy. We have demonstrated that semiconductor quantum dots can be used as 'impedance matching' devices converting high energy X-rays to visible photon range for a simultaneous and mechanistically independent treatment; photodynamic therapy (PDT). Application of quantum dots was limited by it toxicity and relatively low quantum yield with X-ray excitation. To further improve the combined therapy strategy, we synthesize and screen for safer and more efficient nanoparticles. Colloidal GdSe and Gd2O3 nanoparticles were synthesized in octadecene using octylamine and oleic acid as surfactants. The average diameter of the nanoparticles was 10 nm. The samples in organic solution was secured in a light tight box and irradiated by 300 kVp X-rays with a dose rate of 300 cGy/min. The visible photon yield is collected by a lens and transferred to the photomultiplier tube via optic fibers. The average photon counts for 100 seconds were compared between GdSe, Gd2O3 and CdSe quantum dots. Different than quantum dots with fixed band gap and emission peaks, the fluorescent peaks of GdSe and Gd2O3 were excitation light dependent. Shorter emission wavelengths were resulted from higher incident photon energies but the spectra overlap well with the Soret band of porphyrin photosensitizers. While their fluorescence is substantially weaker compared with QDs under UV excitation, fluorescence from both GdSe and Gd2O3 is one order of magnitude stronger than that of QD when excited by 300 kV X-rays. Metal oxide nanoparticle scintillators are more efficient X-ray scintillators than Quantum dots. Moreover, Metal oxide nanoparticle can utilize the Soret band of photosensitizers for more effective energy transfer and excitation. These improvements will reduce the required radiation dose and drug concentration for simultaneous photodynamic therapy.


The roles of the Moran effect and dispersal in synchronizing oscillating populations.
Patterns of spatial synchrony of population dynamics are dramatic phenomena that provide the potential for unraveling forces controlling the dynamics of natural populations in time and space. Prior ecological research has focused on attention to either deterministic or stochastic forces acting separately, with an emphasis on long term behavior, or on small systems consisting often of two interacting spatial locations. Using ideas from the dynamics of weakly coupled oscillators with an emphasis on the temporal dynamics of synchrony we develop a synthetic approach that explains patterns of synchrony as the result of an interplay between deterministic and stochastic forces. The temporal scale of convergence can provide a useful tool for determining the relative importance of deterministic and stochastic influences. Our approach applies both to specific systems that have been previously analyzed such as disease dynamics, and to a range of exploiter victim systems.


Kinetics of the oxidation of p-aminobenzoic acid catalyzed by horseradish peroxidase compounds I and II.
The kinetics of p-aminobenzoic acid oxidation catalyzed by horseradish peroxidase Compounds I and II was investigated intensively as a function of pH at 25 degrees in aqueous solutions of ionic strength 0.11. All of the rate data were collected from single turnover experiments involving reactions of a single enzyme compound. In reactions of both compounds, deviations from first order behavior with respect to the enzyme were observed at high pH values which were explained in terms of a free radical interaction of product with the enzyme. The effect could be eliminated with sufficient excess of substrate. Kinetic behavior which deviated from first order in substrate, observed at low pH, was explained by a mechanism involving an enzyme-substrate complex which reacted with an additional molecule of substrate but at a slower rate. The pH dependence of the second order rate constants for the reaction of p-aminobenzoic acid with free Compounds I and II is similar to results obtained for the comparable reactions of ferrocyanide, suggesting similar proton-transfer mechanisms for both reducing substrates. The reduction of Compound II by p-aminobenzoic acid appeared to be influenced by two ionizable groups on the enzyme which affect the electronic environment of the heme. The lack of influence of substrate ionizable groups on the rate of the Compound II reaction indicated that potential differences in reactivities of NH2C6H4COO- and NH2C6H4COOH were levelled by the diffusion-controlled limit in the acid region of pH. The reduction of Compound I by p-aminobenzoic acid was not diffusion-controlled and the rate-pH profile could be explained in terms of three acid ionizations, two on the substrate and one on Compound I.


C-C and C-H bond activation reactions in N-heterocyclic carbene complexes of ruthenium.
Thermolysis of Ru(PPh3)3(CO)H2 with the N-heterocyclic carbene bis(1,3-(2,4,6-trimethylphenyl)imidazol-2-ylidene) (IMes) results in C-C activation of an Ar-CH3 bond in one of the mesityl rings of the carbene ligand. Upon addition of IMes to Ru(PPh3)3(CO)H2 at room temperature in the presence of an alkene, C-H bond activation is observed instead. The thermodynamics of these C-C and C-H cleavage reactions have been probed using density functional theory.


Construction and identification of a human liver specific microRNA eukaryotic expression vector.
MiR-122 is one of the non-coding RNAs which showed its effects on the lipo-metablism, virus infection and HCC forming through regulation of liver gene expression. Its eukaryotic expression vector was constructed by using pSuper which was widely applied in the siRNA expression. The precursor of human miR-122 gene was amplified by polymerase chain reaction (PCR) from the human genomic DNA. The positive clones were screened by PCR and restriction enzyme digestion. The new expression vector of miR-122 was named pHsa-m122. PHsa-m122 and its controls were transfected to HepG2 cells. The miR-122 expression activity was evaluated by GFP122i sensor reporter plasmid through fluorescence detection and Western blot. It was shown that the fluorescence intensity of GFP122si and pHsa-m122 co-transfection group was weaker than that of the controls, so the functional activity of expressed miR-122 was detected. When HepG2 cells were co-transfected with HBV1.3 and pHsa-m122 plasmids, the results showed miR-122 may down-regulate the gene expression of HBV. The human liver specific microRNA eukaryotic expression vector of miR-122 was constructed successfully, which may facilitate further study of its function in the development of liver virus infection diseases and HCC.


[Spatial distribution of Brucellosis in Gansu province, 2013-2018].
Objective: To analyze the spatial distribution and both hot and cold spots of incidence on Brucellosis in Gansu province from 2013 to 2018. Methods: Based on data from the Infectious Disease Reporting Information System in China, data related to space-time distribution and both hot and cold spots of Brucellosis in Gansu province from 2013 to 2018 were analyzed, by using the ArcGIS 10.5 software and GeoDa 1.6 software. Results: The trend surface analysis showed that the incidence of Brucellosis decreased gradually from the northern to southern parts with slightly higher in the west than in the east of Gansu. Global spatial autocorrelation analysis showed that the Moran's I of Brucellosis in Gansu province from 2013 to 2018 were 0.242, 0.487, 0.424, 0.460, 0.427 and 0.468 (P<0.01), suggesting that the incidence of Brucellosis had spatial clustering features in Gansu province. Local global spatial autocorrelation analysis showed that the number of hot spots were declining in the eastern and north-central regions while the hot spots were increasing in the Hexi area (Wuwei, Zhangye, Jinchang and Jiuquan cities). The cold spots areas were mainly seen in the eastern, southeastern and south of central regions in Gansu province. Conclusions: The incidence of Brucellosis showed obviously spatial clustering characteristics in Gansu province. The number of hot spots were decreasing in the eastern and north of central regions while the hot spots were increasing in the Hexi area, suggesting that the prevention and control measures for Brucellosis should be further strengthened in these areas.


Effects of smoking on pulmonary function and symptomatology in occupationally exposed groups.
Records of 3006 employees of nine companies in southeast Texas screened by a local lung association during the years 1974-1975 were examined to assess the effect of smoking, age, and occupational and residential ambient air pollution exposure. The effects of smoking and occupational exposure were strong when tested against a respiratory morbidity response questionnaire considered to be diagnostic for early-stage bronchitis. Occupational exposure lost statistical significance after place of residence was controlled in the analysis. Smoking and age variables exhibited significant effects when the response variable was pulmonary function test results. The differences between questionnaire and pulmonary function test results may indicate early-stage vs. later-stage respiratory morbidity ascertainment. Agreement in classifying "abnormal" subjects with these two methods decreased with increasing levels of smoking.


Toxic leukoencephalopathy with extrapyramidal dysfunction due to synthetic cannabinoids.
Neurologic sequelae of synthetic cannabinoids are not well understood. We report a case of a woman who developed hyperreflexia, paratonia and cogwheel rigidity after consumption of synthetic cannabinoids. MR imaging demonstrated T2/FLAIR signal enhancement in the supratentorial white matter and globus pallidus internus.


Repellency of Skin-Surface Lipids of Humans to Mosquitoes.
Skin lipids obtained from the washings, in acetone or diethyl ether, of the foreheads or arms of humans are very repellent to female Aedes aegypti when evaluated in a dual-port olfactometer. By means of thin-layer chromatography, the repellent substances can be separated from nonrepellent material also present in skin lipids.


[PHACES syndrome].
PHACES syndrome associates a segmental facial hemangioma with cerebral malformations, aortic branches/cranial arteries anomalies, cardiac defects, eye anomalies or ventral wall defects. The aim of this study is to analyze our experience with this syndrome. Retrospective study of the cases seen at our unit in the last year. We treat 4 cases; 3 girls and 1 child. Besides the segmental hemangioma they presented: 3 vascular cerebral malformations; 2 structural cardiopathies; 2 cerebral malformations, 1 microftalmia. We did not find ventral wall defects. A case received treatment with two cycles of metilprednisolone i.v. and oral prednisone, with favourable course; two cases received initial treatment with oral prednisone continued of oral propanolol in rising pattern up to 2 mg/kg/day, Obtaining both the detention of the tumour growth and regression of the lesion, with very good tolerance. A 7-year-old patient has been treated with colouring pulse laser for her residual lesions. When we see a segmental facial hemangioma we must perform a wide diagnostic study in order to discard a PHACES syndrome. Multidisciplinar approach to the patient by a wide expert's group gets an earlier diagnose and improves the outcome. Propranolol is a promising therapeutic alternative.


Pigmented and thickened axillary folds.
Andrew, 45 years of age, presents with a 12 month history of dark, thickened skin in both axillae. He is concerned about the appearance and would like to know how to treat it. He is moderately obese, with a body mass index (BMI)of 31.2 kg (BMI = weight [kg] + height(2) [m(2)]) but is otherwise well and on no medication. There is no family history of any similar skin disorder.


The Turkish version of the MedRisk instrument for measuring patient satisfaction: measurement properties in physical therapy care among inpatients.
Our aim was to cross culturally adapt the MedRisk instrument for measuring patient satisfaction with physical therapy care for Turkish-speaking inpatients, provide information about its measurement properties, and determine the socio-demographic factors influencing satisfaction of Turkish patients. This was a cross-sectional, measurement-focused study. The MedRisk instrument for measuring patient satisfaction was translated and adapted into Turkish. Two hundred four inpatients with different health conditions from different units of a large university hospital were assessed using the Turkish version of the MedRisk instrument for measuring patient satisfaction. Forty-two patients were reassessed after 72 h. Construct validity, internal consistency, convergent validity, criterion-referenced validity, floor and ceiling effects, and test-retest reliability were evaluated. Factor analysis showed a two-factor structure. Cronbach's alpha values for the internal consistency ranged between 0.49 and 0.81. Corrected item-total correlations ranged between 0.29 and 0.72. Intraclass correlation coefficients ranged between 0.67 and 0.97, standard errors of measurement ranged between 0.34 and 2.61 points, and substantially good agreement was achieved. Eleven of twelve items were positively correlated with the global measures. No floor or ceiling effects were detected. The satisfaction level of inpatients was high. Our results suggested that the Turkish version of the MedRisk instrument for measuring patient satisfaction is a quite reliable and valid measurement to evaluate patient satisfaction with physical therapy care in Turkish-speaking inpatients. We determined that Turkish inpatients are highly satisfied with their physical therapy care, and they consider the patient-physical therapist relationship important. Implications for rehabilitation The Turkish version of the MedRisk instrument for measuring patient satisfaction is a reliable and valid translation of the original MedRisk instrument for measuring patient satisfaction. However, it should be noted that three items from the original version were excluded. Clinicians and relevant researchers can use this instrument to evaluate satisfaction with physical therapy care among Turkish-speaking inpatients.


A tighter bound for the echo state property.
This letter provides a brief explanation of echo state networks (ESNs) and provides a rigorous bound for guaranteeing asymptotic stability of these networks. The stability bounds presented here could aid in the design of echo state networks that would be applicable to control applications where stability is required.


In vivo and in vitro peroxisome proliferation properties of selected clofibrate analogues in the rat. Structure-activity relationships.
We have examined, relative to clofibric acid (CPIB), the effects of a chemical series of phenoxyacetic acids and of two asymmetric CPIB analogues, the R(+)- and S(-)-enantiomers of 2-(4-chlorophenoxy)propionic acid (4-CPPA) and 2-(4-chlorophenoxy)butyric acid (4-CPBA), on hepatic peroxisome proliferation both in vivo and in vitro utilizing cholesterol-fed rats and primary cultured rat hepatocytes respectively. Peroxisome proliferation was assessed by measuring changes in peroxisomal fatty acyl-CoA oxidase (FACO) and microsomal laurate hydroxylase (LH) activities as well as by electron microscopic examination of 3,3'-diaminobenzidine-stained liver slices. CPIB and enantiomers of 4-CPPA and 4-CPBA (0.6 mmol/kg/day for 7 days) produced hepatomegaly, lowered serum cholesterol levels, and caused 4.7- to 12.9-fold and 2.9- to 6.1-fold increases in hepatic FACO and LH activities, respectively, in cholesterol-fed rats. Electron micrographs of liver cells showed an increased number of peroxisomes from cholesterol-fed rats given S(-)-4-CPBA and CPIB. Likewise, these compounds (0.03 to 1.0 mM) induced FACO and LH in primary rat hepatocyte cultures after 72 hr. R(+)- and S(-)-Enantiomers of 4-CPPA produced similar concentration-dependent and maximal increases in both FACO and LH activities, whereas enantiomeric selectivity [S(-) greater than R(+)] for the induction of these two enzymes was observed with the isomers of 4-CPBA. The increases in the activities of FACO and LH caused by S(-)-4-CPBA were similar to those elicited by 1.0 mM CPIB (58.6- and 9.8-fold respectively). These results show that the enantiomers of 4-CPPA and 4-CPBA induce the peroxisome proliferation-associated enzymes FACO and LH in vivo and in vitro, and that the S(-)-isomer of 4-CPBA causes a greater induction of FACO and LH in vitro than its corresponding R(+)-isomer, indicating that these two enzymes are induced in an enantioselective manner. Optimal induction of the peroxisome proliferation-associated enzymes FACO and LH in rat hepatocyte cultures was produced by phenoxyacetic acids possessing (1) a chlorine atom at the 4-position of the phenyl ring, (2) a dimethyl or mono-ethyl substitution at the alpha-carbon atom of the carboxylic acid side chain; and (3) an S(-)-orientation for chiral analogues possessing a mono-ethyl group at the alpha-carbon atom of the carboxylic acid side chain.(ABSTRACT TRUNCATED AT 400 WORDS)


Postural control as assessed with virtual reality.
We studied the use of virtual reality technology as a stimulus in balance examinations. A pilot study was made using a small group of healthy subjects to investigate the effect of alcohol and virtual reality stimulus on the subjects' balance. The tests showed that blood alcohol concentration accounted for almost 50% of the increased lateral body sway velocity. The new stimulus technique based on virtual reality technology seems to be effective and flexible for postural investigations.


Association of Mycoplasma pneumoniae infection with Henoch-Schonlein purpura.
We present a child with Henoch-Schonlein purpura and Mycoplasma pneumoniae infection, an association that was rarely described in the literature. The infection was confirmed serologically and by using PCR.


Day-of-injury CT as an index to pre-injury brain morphology: degree of post-injury degenerative changes identified by CT and MR neuroimaging.
A detailed case study is presented in which pre-injury CT scan findings are compared and contrasted with post-injury CT and MR results in a case of traumatic brain injury (TBI). The day-of-injury scan represented an adequate estimate of pre-injury morphological status based on cross-sectional area measurements of the ventricular system. By comparing pre-injury CT measurements with those obtained on the day of injury, 2 days post-injury and 16 months post-injury via assessing cross-sectional area of select ventricular regions (e.g. anterior and temporal horns, body and third ventricle) it was demonstrated that the TBI induced over a 50% ventricular expansion. Such ventricular expansions are felt to provide some index into diffuse axonal injury which may provide a means of eventually quantifying the degree of structural damage secondary to TBI. This analysis also demonstrated that there were no significant differences between selected cross-sectional ventricular areas in the 15 day and 16 month post-injury MR scans. This finding suggests that the degenerative effects of TBI have a rapid onset and are becoming readily apparent by 15 days post-injury. Thus, early imaging may provide a good index of long-term morphological outcome in TBI.


Normal palatal sutures in newborns and fetuses: a critical fact for successful palatal distraction.
Distraction osteogenesis (DO) has recently been applied to the palate. Successful posterior lengthening and medial advancement of the palates was continuously reported. Based on these studies, it is obvious that DO will play a major role in the management of problems related to palatal defects in the near future. Although the results are appealing, they may not be applicable for humans due to anatomic differences. All experimental studies used normal palatal sutures of young dogs for size expansion. Therefore, it is necessary to know normal palatal sutures in infants before one can clinically apply this new technique. With consent, palates of fetuses and neonates who died of various causes were examined. Eight fresh cadavers were available for the dissection, with two being skeletonized using the boiling process. There were three fetal deaths in utero (33-41 weeks of gestational age) and five postnatal deaths (aged between 5 hours and 6 months). All specimens were grossly normal in shape and size except for one with a unilateral complete cleft of lip and palate. A midline palatal suture was found in every noncleft specimen, while premaxillary and transverse palatomaxillary sutures were present in every specimen. Laterally, there was no true suture except for the most posterior portion, which was contiguous with the greater palatine foramen. The palatal sutures of third-trimester fetuses and neonates are not different from adult ones. There is no lateral suture that will allow distraction in the medial direction. It is only the posterior hard palate (palatine bones) that can potentially be moved medially and posteriorly by sutural expansion with DO.


Trigeminal neuralgia and cerebellopontine-angle lipoma in a child.
Trigeminal neuralgia and cerebellopontine-angle lipomas are very rare in children. We describe the history and findings of an 8-year-old boy with right trigeminal neuralgia and a lipoma detected by magnetic resonance imaging at the level of the root-entry zone of the right seventh cranial nerve. We propose a possible mechanism of infiltration of the trigeminal rootlets by the lipoma.


Side scattering shadow and energy concentration effects of epsilon-near-zero media.
By analytically and numerically investigating the near-field scattering properties of particles composed of epsilon-near-zero (ENZ) media, we reveal a unique scattering phenomenon which is hereby denoted as the side scattering shadow and energy concentration effect. The scattering of ENZ particles leads to the emergence of near-field "shadows," where the electric fields are significantly decreased to zero on two sides of the particle perpendicular to the incident direction. At the same time, the electric fields inside the particle are enhanced to a certain extent, indicating concentration of wave energy. These extraordinary behaviors can be well explained through the Mie scattering theory. Moreover, such unique effects robustly exist for isotropic and anisotropic ENZ particles of almost arbitrary shapes and with loss. We further demonstrate interesting applications of this effect, including the "quenching" of surface plasmons and the concentration of electromagnetic energy in the deep subwavelength scale. Our findings may inspire novel applications in nanophotonics.


Nephrotoxic effects of unleaded petrol in female rats.
Female Wistar rats were exposed to 4 g m-3 unleaded petrol for 8 h a day, 5 days a week for 60 days. Urinary beta 2-microglobulin (beta 2-m), lactate dehydrogenase (LDH) and lysozyme were used as markers of tubular dysfunction. Urinary excretion of albumin and the glomerular filtration rate (GFR) were used as indicators of glomerular impairment. There were no statistically significant changes in the GFR or urinary albumin concentrations in the exposed group. Petrol exposure induced an increase of beta 2-m, total proteins, lysozyme and LDH excretion, but only beta 2-m was increased significantly. Our results show that subchronic exposure to high levels of unleaded petrol induced only a mild proximal tubular dysfunction in female rats.


Wear of dental sealing materials using the replication technique.
The aim of the present study was an in vivo evaluation of the wear of different sealing materials using the replication technique. Four different sealing materials were randomly applied on 2 out of 4 caries-free permanent first molars of each patient. Impressions were taken at T0: before the sealing material was applied; T1: right after the application; T2: 6 months after the application, and T3: 1 year after the application. The impressions were then processed for scanning electron microscopy analysis of the wear of the examined materials. Statistical analysis was used to evaluate differences among and within the 4 groups. At T2, the average ratio of residual material in all the groups was 62.37% ± 1.21%, while at T3 it was 49.63% ± 1.11%. At both T2 and T3 there were no statistically significant differences among the 4 groups examined (p=0.76 and p=0.50 respectively). Comparison within the same group at T2 and T3 showed that statistically significant differences were only detected in group D (p=0.015). Sealing materials do not undergo a complete loss after 1 year of application, thus indicating that they are suitable for caries prevention.


Synthesis of multibranched australine derivatives from reducing castanospermine analogues through the Amadori rearrangement of gem-diamine intermediates: selective inhibitors of β-glucosidase.
A practical one-pot synthesis of bi- and triantennated australine analogues from a pivotal sp(2)-iminosugar-type reducing castanospermine precursor is reported. The transformation involves a gem-diamine intermediate that undergoes the indolizidine → pyrrolizidine Amadori-type rearrangement and proceeds under strict control of the generalized anomeric effect to afford a single diastereomer. The final compounds behave as selective competitive inhibitors of β-glucosidase and are promising candidates as pharmacological chaperones for Gaucher disease.


Chemical synthesis and some properties of 6-substituted flavins.
A number of derivatives of riboflavin and of 3-methyllumiflavin substituted in the 6 position have been synthesized starting with 6-nitro flavins, reduction to the 6-amino flavin, and diazotization, followed by reaction with the appropriate nucleophile. The absorption spectra, oxidation-reduction potentials, and the electron spin resonance spectra of the radical cationic forms of several of these synthetic compounds have been determined, including 6-S-cysteinyl-3-methyllumiflavin and 6-S-cysteinylriboflavin. The latter has been shown to be identical with the dephosphorylated form of the aminoacyl flavin isolated from trimethylamine dehydrogenase [Steenkamp, D. J., Kenney, W. C. & Singer, T. P. (1978) J. Biol. Chem. 253, 2812-2817; Steenkamp, D. J., McIntire, W., & Kenney, W. C. (1978) J. Biol. Chem. 253, 2818-2824] in regard to absorption specturm, photochemical properties, and mobility in high-voltage electrophoresis and in thin-layer chromatography. An unusually pronounced interaction between the amino group and the isoalloxazine ring system was deduced from the absorption spectra of 6-amino-3-methyllumiflavin and 6-aminoriboflavin.


[Influences of arbuscular mycorrhizal fungus and phosphorus level on the lateral root formation of tomato seedlings].
To explore the influences of arbuscular mycorrhizal fungi (AMF) and P level on plant root system architecture, tomato seedlings were inoculated with AMF strain Rhizophagus irregularis BGC JX04B under two P levels, and the influences of AMF and P level on lateral root (LR) formation of tomato seedlings were studied. Results indicated that the promoting effect of AMF on plant biomass was not evident, but significantly decreased the root to shoot ratio of plants. AMF significantly increased the primary root length but decreased the 1st order LR length and interacted with the mycorrhizal colonization period. AMF significantly lowered the 2nd-3rd order LR number and the ratio of 2nd order LR number to 1st order LR number, but did not significantly affect the 1st-2nd order LR density. High P level (50 mg x kg(-1) P) significantly promoted the plant growth and decreased the root to shoot ratio of plants. It had no significant effect on the primary root length and the 1st order root length, but significantly enhanced the 1st-3rd order LR number and the ratio of 2nd order LR number to P order LR number, increased the 1st-2nd order LR density. It suggested that AMF and P level did not share a common mechanism to influence the LR formation of tomato plants. The influence of high P level may depend on its promoting effects on nutrient uptake and plant growth, while the influence of AMF is more complex. Furthermore, the interaction between AMF and mycorrhizal colonization period implies the possible involvement of carbohydrate distribution (sugar signaling) in the regulation of root system architecture by AMF.


Fluorescence, turn-on detection of melamine based on its dual functions as fluorescence enhancer of DNA-AgNCs and Hg(II)-scavenger.
A new method has been developed for the simple, fluorescence, turn-on detection of melamine, which utilizes DNA-templated silver nanoclusters (DNA-AgNCs) as a key component. In the sensor, melamine exhibits the dual functions: one is to enhance the fluorescence signal of DNA-AgNCs by its specific interaction with thymine residues in DNA template, and the other is to prevent Hg(II)-induced fluorescence quenching of DNA-AgNCs via its strong coordination with Hg(II). These consequently enable the sensitive and selective detection of melamine. By exploiting such novel features of melamine, we significantly increased the fluorescence response up to 360%, compared to the previous counterpart that relies on DNA-AgNCs only, and successfully determined melamine down to ca. 49 nM, a value that is 400 times lower than the safety level of 20 μM set by the US Food and Drug Administration. In addition, it was confirmed that the proposed approach works fine even in the real milk samples without any additional pre-treatment steps.


Risk factors for early hospital readmission in low-income elderly adults.
To identify risk factors for early hospital readmission in low-income community-dwelling older adults. Prospective cohort study. University-affiliated urban safety-net healthcare system in Indianapolis, Indiana. Community-dwelling adults aged 65 and older with annual income less than 200% of the federal poverty level and enrolled in the Geriatric Resources for Assessment and Care of Elders (GRACE) randomized controlled trial (N = 951). Participant health and functional status at baseline and 6, 12, 18, and 24 months. Early readmission was defined as a repeat hospitalization occurring within 30 days of a prior hospital discharge. Candidate risk factors included sociodemographic characteristics, health and functional status, prior care, lifestyle, and satisfaction with care. Of 457 index admissions in 328 participants, 85 (19%) were followed by an early readmission. The independent risk factors for early readmission identified according to regression analysis were living alone (odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.02-2.87), fair or poor satisfaction with primary care physician (OR = 2.12, 95% CI = 1.01-4.46), not having Medicaid (OR = 1.80, 95% CI = 1.05-3.11), receiving a new assistive device in the past 6 months (OR = 2.26, 95% CI = 1.26-4.05), and staying in a nursing home in the past 6 months (OR = 5.08, 95% CI = 1.56-16.53). Age, race, sex, education, and chronic diseases were not associated with early readmission. A broad range of nonmedical risk factors played a greater role than previously recognized in early hospital readmission of low-income seniors.


Preparation of a carbon ceramic electrode modified by 4-(2-pyridylazo)-resorcinol for determination of trace amounts of silver.
A 4-(2-pyridylazo)-resorcinol (PAR)-modified carbon ceramic electrode (CCE) prepared by the sol-gel technique has been reported for the first time in this paper. By immersing the CCE in aqueous solution of PAR (0.001molL(-1)), after a short period of time, a thin film of PAR was rapidly formed on the surface of the electrode due to its strong adsorption properties. A differential pulse anodic stripping voltammetric (DPASV) method was developed for determination of Ag(I) at the modified carbon ceramic electrode. The analysis procedure consisted of an open circuit accumulation step in a sample solution which was continuously stirred for 12 min. This was followed by replacing the medium with a clean solution where the accumulated Ag(I) was reduced for 15s in -0.6 V. Then, the potential was scanned from -0.2 to +0.2V to obtain the voltammetric peak. The detection limit of silver(I) was 0.123 microg L(-1), and for seven successive determinations of 10, 100 and 200 microg L(-1) Ag(I), the relative standard deviations were 2.1, 1.4 and 1.03%, respectively. The calibration curve was linear for 0.5-300 microg L(-1) silver(I). The procedure was applied to determine silver(I) in X-ray photographic films and super-alloy samples.


Correction of posterior shoulder tightness is associated with symptom resolution in patients with internal impingement.
Glenohumeral internal rotation deficit (GIRD) and posterior shoulder tightness have been linked to internal impingement. To determine if improvements in GIRD and/or decreased posterior shoulder tightness are associated with a resolution of symptoms. Cohort study; Level of evidence, 3. Passive internal rotation and external rotation (ER) range of motion (ROM) at 90 degrees of shoulder abduction and posterior shoulder tightness (cross-chest adduction in side lying) were assessed in 22 patients with internal impingement (11 men, 11 women; age 41 +/- 13 years). Treatment involved stretching and mobilization of the posterior shoulder. The Simple Shoulder Test (SST) was administered on initial evaluation and discharge. Changes in GIRD, ER ROM, and posterior shoulder tightness were compared between patients with complete resolution of symptoms versus patients with residual symptoms using independent t tests. Patients had significant GIRD (35 degrees), loss of ER ROM (23 degrees), and posterior shoulder tightness (35 degrees) on initial evaluation (all P < .01). Physical therapy (7 +/- 2 weeks; range, 3-12 weeks) improved GIRD (26 degrees +/- 14 degrees; P < .01), ER ROM loss (14 degrees +/- 20 degrees), and posterior shoulder tightness (27 degrees +/-19 degrees). The SST improved from 5 +/- 3 to 11 +/- 1 (P < .01). A greater improvement in posterior shoulder tightness was seen in patients with complete resolution of symptoms (n = 12) compared with patients with residual symptoms (35 degrees vs 18 degrees; P < .05). Improvements in GIRD and ER ROM loss were not different between groups (GIRD, 25 degrees vs 28 degrees, P = .57; ER ROM, 14 degrees vs 15 degrees, P = .84). Resolution of symptoms after physical therapy treatment for internal impingement was related to correction of posterior shoulder tightness but not correction of GIRD.


Drug treatment-related factors of inadequate seizure control.
To optimize seizure control it is important to identify modifiable factors. We conducted a case-control study to explore to what extent drug treatment-related factors are associated with seizures. Eighty-six patients with epilepsy were evaluated: 45 cases (recently experienced a seizure) and 41 controls (seizure-free for at least 2 months). There was a significant association between low AED serum concentration and seizures (odds ratio (OR)=8.9, 95% confidence interval (CI)=1.7-47.8), compliance was not associated with seizures (OR=0.9, 95% CI=0.2-4.0), and changes in medication (mainly non-AEDs) were more frequently observed in the case group than in the control group (OR=4.1, 95% CI=0.9-18.3). These findings indicate that patients with low AED serum levels have a nine times higher risk of seizures compared with patients with therapeutic AED levels and that changes in medication regimens in patients with epilepsy should be made with care.


Hydroxylation and translational adaptation to stress: some answers lie beyond the STOP codon.
Regulation of protein synthesis contributes to maintenance of homeostasis and adaptation to environmental changes. mRNA translation is controlled at various levels including initiation, elongation and termination, through post-transcriptional/translational modifications of components of the protein synthesis machinery. Recently, protein and RNA hydroxylation have emerged as important enzymatic modifications of tRNAs, elongation and termination factors, as well as ribosomal proteins. These modifications enable a correct STOP codon recognition, ensuring translational fidelity. Recent studies are starting to show that STOP codon read-through is related to the ability of the cell to cope with different types of stress, such as oxidative and chemical insults, while correlations between defects in hydroxylation of protein synthesis components and STOP codon read-through are beginning to emerge. In this review we will discuss our current knowledge of protein synthesis regulation through hydroxylation of components of the translation machinery, with special focus on STOP codon recognition. We speculate on the possibility that programmed STOP codon read-through, modulated by hydroxylation of components of the protein synthesis machinery, is part of a concerted cellular response to stress.


IL-17F/IL-17R interaction stimulates granulopoiesis in mice.
IL-17F, a member of the interleukin (IL)-17 cytokine family, most closely resembles IL-17A structurally. IL-17A is a potent stimulator of granulopoiesis; its expression is induced in response to microbial challenge. Although IL-17F is considered to be a weak IL-17A analog that is also mediating its effect via IL-17R, its exact role and in vivo functions are unknown. Our goal was to determine the in vivo activity of IL-17F on granulopoiesis as well as on release of granulopoiesis-stimulating downstream cytokines in mice and directly compare its effect to IL-17A. Murine IL-17A (mIL-17A) or IL-17F (mIL-17F) was expressed in vivo in C57BL6 mice using adenoviral gene transfer technology. Peripheral cell counts were assessed as well as hematopoietic precursors using colony-forming assays at set time points. Downstream cytokines were measured using enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction. We found mIL-17F to have similar expression kinetics as mIL-17A in splenocytes in vitro and in vivo, following challenge with microbial agents. Overexpression of mIL-17F in vivo resulted in similar neutrophilia and only in slightly reduced myeloid progenitor expansion when compared to mIL-17A. In vivo, there was no difference in releases for granulocyte-macrophage colony-stimulating factor; regulated on activation, normal T expressed and secreted; interferon-inducible protein-10; IL-6; and monocyte chemotactic protein-1 between either cytokine. IL-1A, macrophage inflammatory protein -2 (MIP), KC, and granulocyte colony-stimulating factor expression was approximately half of that seen with mIL-17A. Both IL-17A and IL-17F are induced by similar stimuli, have similar expression kinetics and despite only minimal in vitro activity for IL-17F, surprisingly they exert similar in vivo bioactivity. IL-17F bioactivity appears to be augmented in vivo through mechanisms that require further investigation.


The role of oral 1C antiarrhythmic drugs in terminating atrial fibrillation.
Antiarrhythmic drug therapy still remains the mainstay in the management of many supraventricular and ventricular arrhythmias. Several studies have recently pointed out the role of orally administered class 1C drugs in terminating atrial fibrillation. These drugs can play an important role in the ambulatory management of selected patients. The electrophysiologic mechanisms of these antiarrhythmic drugs together with their pharmacologic properties and clinical indications are discussed according to the current literature.


Finite-size scaling in complex networks.
A finite-size-scaling (FSS) theory is proposed for various models in complex networks. In particular, we focus on the FSS exponent, which plays a crucial role in analyzing numerical data for finite-size systems. Based on the droplet-excitation (hyperscaling) argument, we conjecture the values of the FSS exponents for the Ising model, the susceptible-infected-susceptible model, and the contact process, all of which are confirmed reasonably well in numerical simulations.


Cannabis use and striatal D2 receptor density in untreated first-episode psychosis: an in vivo SPECT study.
The biological basis of the association between cannabis-induced dopamine dysregulation and psychosis remains poorly understood. This (123)I-IBZM SPECT study assessed striatal dopamine D2 receptor (D2R) binding in 37 untreated first-episode psychosis (FEP) subjects, and 18 healthy controls. The aim was to examine if there were differences between FEP subjects with (n=14) and without (n=23) cannabis use in uptake ratios in the D2R. Striatal/Frontal cortex (S/F) uptake ratios were obtained. Healthy controls showed the lowest D2R binding ratios. No differences were found in S/F ratios between users and non-users, suggesting similar dopaminergic mechanisms underlying psychotic symptoms in both groups.


[Immune-mediated tubulointerstitial injury in hemorrhagic fever with renal syndrome].
To study the presence of Hantan virus RNA and specific immune-complex deposits in the renal tubular epithelium of HFRS patients. Renal biopsy specimens from 15 cases of HFRS, 3 cases of ischemic ATN and 5 normal controls (donor of transplantation) were investigated. Human HLA-DR, ICAM-ILFA-1 and CD4+, CD8+, CD8+ cells in the renal tissue section were quatitatively analyzed by immuno-peroxidase staining 4 layers PAP. Histo-morphometric analysis of pathological section was made for each specimen. HFRS presented abundant amount of HLA-DR and ICAM-1 in tubular cells both on cortical and medullary region, while ischemic ATN tended to have such positive results only in cells of cortical region. The intensity and extent of HLA-DR and ICAM-1 LFA-1 staining were closely correlated with the degree of tubulointerstitial damage of HFRS. Interstitial CD4, CD8 and monocytes increased in amount profoundly in HFRS with a preponderance in the medullary region, and particularly of CD8 positive cells. Less marked increment occurred in ATN cases, and no discrepancies were found between cortical and medullary region or cell types. The severity of tubulointerstitial lesion was closely associated with the extent of cellular infiltration and the expression of HLA-DR, ICAM-1 in renal tubular cells. The characteristic changes of tubulointerstitial lesions in HFRS suggest that virus infection may be one of the mediators responsible for the immune kidney injuries in HFRS.


Is it acceptable for medical professionals to kiss paediatric patients?
It is human nature, perhaps more so for doctors and nurses, to comfort children in distress. Unfortunately, however, necessary medical procedures carried out by healthcare providers (eg, venipuncture) can often result in pain and discomfort, which may in turn cause the provider a degree of guilt and distress. Is it ever acceptable to comfort a paediatric patient with a kiss? This essay examines the literature published on this subject reflecting on a recent encounter with a patient.


Advances and strategies for spinal cord regeneration.
Although a cure for spinal cord injuries does not currently exist, advances have been made in the field of spinal cord regeneration. This article discusses the pathophysiology of spinal cord injury, animal models, and strategies for restoration and regeneration of the spinal cord.


A rare case of peritoneal dialysis-related peritonitis caused by goldfish water tankderived Aeromonas hydrophila.
A 62-year-old man was diagnosed with peritoneal dialysis (PD)-related peritonitis following diarrhea and determination of a dialysate leukocyte count of 10,224/μL. We cultured peritoneal effluent and started intraperitoneal antibiotic therapy. Peritonitis immediately improved. Peritoneal effluent culture yielded Aeromonas hydrophila. The medical interview revealed that the patient kept goldfish as pets. We suspected that the fish tank water was the source of the infection, considering the association of A. hydrophila with aquatic environments. Culturing of tank water confirmed the presence of Aeromonas. Furthermore, we observed that one of the goldfish was suffering from lepidorthosis, which is commonly caused by Aeromonas, and we then confirmed that the fish's infection was caused by an aeromonad. Aeromonas species have rarely been identified as the pathogens in PD-related peritonitis; to our knowledge, there hitherto have been no reports identifying the source of this organism. We present here the process of this infection as elucidated through investigation of the living environment of the patient.