Routes for renal transport of methylmercury in mice.
To clarify the routes for renal methylmercury uptake, the effects of ureter ligation and pretreatment of probenecid, an organic anion transport inhibitor, or acivicin, a gamma-glutamyltranspeptidase (gamma-GTP) inhibitor, on renal methylmercury content were investigated in mice. For 120 min after CH3HgCl (5 mumol/kg, i.v.) injection, renal methylmercury content in bilateral ureter-ligated mice was approximately 50% lower than that of sham-operate mice. The glomerular filtration rate was reduced to about 15% of the control by ureter ligation. These results suggest an important role of glomerular filtration in the renal methylmercury uptake. Pretreatment with probenecid (0.5 or 1.0 mmol/kg, i.p.) reduced the renal methylmercury accumulation 30 min after CH3HgCl injection in a dose-dependent manner in both ureter-ligated and sham-operated mice. Urinary methylmercury excretion was not affected by probenecid pretreatment. Renal methylmercury content of ureter-ligated mice was not changed by pretreatment with acivicin (0.5 or 1.0 mmol/kg. i.p.), which was previously reported to decrease the renal methylmercury content in mice. Coadministration of GSH (10 mumol/kg, i.v.) with CH3HgCl increased the renal methylmercury uptake determined 5 min after injection in ureter-ligated mice. These results suggest that at least two transport systems play major roles in renal methylmercury uptake: one is a route from the glomeruli through the brush border membrane which is dependent on the action of gamma-GTP, and the other route is the one using an organic anion transport system through the basolateral membrane.


Kardar-Parisi-Zhang interfaces bounded by long-ranged potentials.
We study unbinding transitions of a nonequilibrium Kardar-Parisi-Zhang interface in the presence of long-ranged substrates. Both attractive and repulsive substrates, as well as positive and negative Kardar-Parisi-Zhang nonlinearities, are considered, leading to four different physical situations. A detailed comparison with equilibrium wetting transitions as well as with nonequilibrium unbinding transitions in systems with short-ranged forces is presented, yielding a comprehensive picture of unbinding transitions and of their classification into universality classes. These nonequilibrium transitions may play a crucial role in the dynamics of the wetting or growth of systems with intrinsic anisotropies.


Anisotropic smoothing regularization (AnSR) in Thirion's Demons registration evaluates brain MRI tissue changes post-laser ablation.
MRI-guided laser-induced interstitial thermal therapy (LITT) is a form of laser ablation and a potential alternative to craniotomy in treating glioblastoma multiforme (GBM) and epilepsy patients, but its effectiveness has yet to be fully evaluated. One way of assessing short-term treatment of LITT is by evaluating changes in post-treatment MRI as a measure of response. Alignment of pre- and post-LITT MRI in GBM and epilepsy patients via nonrigid registration is necessary to detect subtle localized treatment changes on imaging, which can then be correlated with patient outcome. A popular deformable registration scheme in the context of brain imaging is Thirion's Demons algorithm, but its flexibility often introduces artifacts without physical significance, which has conventionally been corrected by Gaussian smoothing of the deformation field. In order to prevent such artifacts, we instead present the Anisotropic smoothing regularizer (AnSR) which utilizes edge-detection and denoising within the Demons framework to regularize the deformation field at each iteration of the registration more aggressively in regions of homogeneously oriented displacements while simultaneously regularizing less aggressively in areas containing heterogeneous local deformation and tissue interfaces. In contrast, the conventional Gaussian smoothing regularizer (GaSR) uniformly averages over the entire deformation field, without carefully accounting for transitions across tissue boundaries and local displacements in the deformation field. In this work we employ AnSR within the Demons algorithm and perform pairwise registration on 2D synthetic brain MRI with and without noise after inducing a deformation that models shrinkage of the target region expected from LITT. We also applied Demons with AnSR for registering clinical T1-weighted MRI for one epilepsy and one GBM patient pre- and post-LITT. Our results demonstrate that by maintaining select displacements in the deformation field, AnSR outperforms both GaSR and no regularizer (NoR) in terms of normalized sum of squared differences (NSSD) with values such as 0.743, 0.807, and 1.000, respectively, for GBM.


Immature platelet fraction predicts coagulopathy-related platelet consumption and mortality in patients with sepsis.
The diagnostic and prognostic value of immature platelet fraction (IPF) in sepsis has not been determined. This study aimed to assess whether IPF is an early predictor of platelet decline due to coagulopathy and is associated with mortality in patients with sepsis. In total, 149 patients with a platelet count of ≥80×10(3)/μL on intensive care unit admission (101 with sepsis, 48 controls without sepsis) were prospectively evaluated. We measured IPF on admission and observed for development of subsequent platelet count decline (defined as a >30% decrease or <80×10(3)/μL) in 5days, and mortality at 28days. The absolute immature platelet count (AIPC) was calculated to evaluate thrombopoiesis. Forty-seven patients with sepsis subsequently developed a decrease in platelet count. The IPF was highest in patients whose platelet count decreased, followed by patients without a decrease in platelet count and controls (median, 4.3% [3.1%-8.1%] vs. 3.7% [2.6%-4.6%] vs. 2.1% [1.6%-3.5%], respectively; P<0.0001). The AIPC was similar in patients with and without a decrease in platelet count (7.6 [4.2-10.0] vs. 5.9 [4.2-8.7]×10(3)/μL, respectively; P=0.32). Coagulation derangement was more severe in patients who did than did not subsequently develop a decreased platelet count. Cox regression and receiver operator characteristic curve analysis revealed that IPF was a strong independent predictor of mortality, with accuracy similar to a standard prognostic scoring system. The admission IPF in septic patients predicts a subsequent decrease in platelet count, indicating platelet consumption with ongoing coagulopathy and risk of poor prognosis.


Radical generation and alterations of erythrocyte integrity as bioindicators of diagnostic or prognostic value in COPD?
Chronic obstructive pulmonary disease (COPD) has recently been viewed as an inflammation-dependent systemic disease. Oxidative modifications in the pulmonary microenvironment can result in a number of functional changes in pulmonary tissue as well as in the blood. Studies have been carried out to detect whether oxidatively modified molecules or cells could be considered possible markers of the disease. We hypothesize here that new insights into COPD could come from enzymes involved in deliberate radical generation (i.e., Nox and NOS family enzymes) as well as from alterations of erythrocyte integrity and function, which could become bioindicators of diagnostic or prognostic value in the near future.


Prenatal dexamethasone administration disrupts the pattern of cellular development in rat lung.
To examine whether prenatal exposure to glucocorticoids could adversely affect subsequent cellular development of the lung, we administered 0.2 mg/kg of dexamethasone to pregnant rats on gestational days 17, 18, and 19. Lungs of the offspring were then examined for patterns of cell acquisition (DNA) and growth (protein). DNA concentration (a marker of cell packing density) and DNA content (a measure of total cell numbers) were reduced during gestation, and the shortfalls in concentration persisted past weaning. Disruption of development was also apparent in the protein/DNA ratio, which was consistently elevated, a finding consistent with cellular hypertrophy. In addition, lung ODC became coupled to beta-adrenergic receptors prematurely in the dexamethasone group, suggesting that neural control of tissue differentiation is altered. These data indicate that prenatal glucocorticoids may compromise lung development through effects on cell replication and differentiation, which derive, in part, from alterations in the reception of trophic neural signals.


Uptake of horseradish peroxidase by presynaptic terminals of bipolar cells and photoreceptors of the from retina.
The uptake of horseradish peroxidase (HRP) into synaptic vesicles of presynaptic terminals in the inner and outer plexiform layers of isolated frog retinas was studies by electron microscopy. Uptake into the terminals of bipolar cells was found to be enhanced by exposure of the preparations to elevated concentrations of potassium ions, and by exposure to aspartic acid or glutamic acid. Glycine had much less effect on the terminals. These results suggest that HRP uptake may prove useful in monitoring some aspects of the responses of inner plexiform layer cells to conditions of physiological interest. Uptake into photoreceptor terminals was also enhanced by elevated potassium concentrations; the effects of the amino acids were complex.


A Giant Lymphangioma on the Neck.
Lymphangioma is a congenital malformation of the lymphatic system, which is located mostly on the head and neck region. Most of the cases are seen at age younger 2 years. It is rare in adult population and when detected, it can be treated with surgical excision. We present a 50-year-old patient with giant lymphangioma on the posterior cervical region of the neck treated by surgical treatment successfully.


Topical fibronectin in the treatment of persistent corneal epithelial defects and trophic ulcers.
Six patients with persistent corneal epithelial defects that failed to improve with standard therapy were treated with topical fibronectin in a phase I uncontrolled trial. Fibronectin was purified from autologous plasma by affinity chromatography and administered topically, 0.5 mg/ml five times a day, for three weeks. Complete reepithelialization was achieved in five patients: three healed three to 17 days after initiation of treatment while two healed one to two weeks after discontinuation of topical fibronectin. No side effects were observed. Over a follow-up period of three to 18 months, two recurrences were noted.


Cerebral 2-deoxyglucose uptake in rats during ethanol withdrawal and postwithdrawal.
The overt ethanol withdrawal syndrome is associated with a generalized increase in cerebral uptake of 2-deoxyglucose. Relatively high elevations of 2-deoxyglucose were observed in many structures associated with motor function, the mamillary body-anterior thalamus-cingulate cortex pathway, many thalamic nuclei, and the raphe. Overtly withdrawing rats had higher levels of 2-deoxyglucose than postwithdrawing animals that had been abstinent for 1-5 weeks in 96% of the gray areas evaluated. Postwithdrawal was associated with increased amounts of 2-deoxyglucose in comparison to controls in 80% of the gray areas evaluated. Postwithdrawal and control rats did not differ in some areas involved with motor function and some limbic structures, such as the mamillary body-anterior thalamus-cingulate cortex pathway. It is concluded that the ethanol-withdrawal syndrome results in alterations in cerebral physiology, some of which persist for at least 5 weeks postwithdrawal.


Neonatal jaundice is associated with a small increase in the risk of childhood type 1 diabetes: a meta-analysis of observational studies.
Published data on the role of neonatal jaundice as a risk factor for childhood type 1 diabetes mellitus is inconsistent. We aimed to review systematically, the evidence for an increased risk of type 1 diabetes in children diagnosed with neonatal jaundice. A comprehensive search of the published literature was performed to identify studies that had recorded the occurrence of neonatal jaundice in a group of children with type 1 diabetes and in a group of control children. Odds ratios (ORs) were extracted from reports or derived from tabulated data and then combined using a random effects meta-analysis. Data were available from 12 case-control studies and one retrospective cohort study. Overall, there was only weak evidence of an increase in the risk of type 1 diabetes in children who had neonatal jaundice (OR 1.14, 95% CI 0.99-1.32; P = 0.07), and there was some evidence of heterogeneity (I(2) = 53%, P = 0.01) mainly attributable to one study. An analysis restricted to studies not relying on parental recall showed a stronger, significant relationship (OR = 1.25, 95% CI 1.03-1.51; P = 0.02), although heterogeneity remained. This analysis found evidence of a small but statistically significant increase in childhood type 1 diabetes risk associated with neonatal jaundice but only for studies which used data from obstetric records. Jaundice caused by blood group incompatibility or requiring phototherapy may be associated with a greater increase in type 1 diabetes risk and deserves further study.


Interaction of amide inhibitors with the active site of carbonic anhydrase: metal-induced deprotonation of the bound amide group is indicated by slow binding kinetics, by visible spectra of complexes with cobalt enzyme, and by pH effects on binding affinity.
Most carbonic anhydrase (CA) inhibitors bind at the active site metal and either are anions or are capable of deprotonation to yield anions. Much less is known about the interaction of CA with inhibitors that have hitherto been considered to bind as neutral species. We report a study of the reversible amide inhibition of Co(II)-substituted CA by iodoacetamide and ethyl carbamate (urethane), as well as the ambivalent oxamate, the monoamide of oxalate. Visible cobalt spectral changes indicate coordination of all these inhibitors to the metal. The pH dependence of the affinity of carbonic anhydrase isozyme I (CA I) for ethyl carbamate and iodoacetamide is formally consistent with their binding either as anionic species to the acid form of the enzyme or as neutral species to the basic form of the enzyme. The former view is in better accord with the spectral data. Most strikingly, reversible binding of iodoacetamide and ethyl carbamate leads to uniquely slow kinetics of ligand association and dissociation that could be followed by simple mixing. The slow association kinetics suggest the involvement of energetically unfavorable deprotonation of the amide group preceding final coordination. The complex pH profile for inhibition of CA I by the ambivalent oxamate is consistent with coordination through the carboxylate group at low pH and through the deprotonated amide group at high pH. The visible spectrum of the complex of Co(II)CA I with oxamate shows a parallel dependence on pH, reflecting this dual coordination mode. Similarly, oxamate dissociation kinetics were biphasic and could be correlated with the pH-dependent spectral changes.(ABSTRACT TRUNCATED AT 250 WORDS)


Anal skin tags: removal made simple.
Anal skin tags are a common finding. They are found in one-third of patients with bening anal disorders. We describe a simple method of anal skin tag removal during stapled anopexy. This involves utilizing the circular anal dilator provided with the stapling kit. Skin tags are brought through the perforations of the circular anal dilator of the stapling kit. The skin tags are removed by cautery. Minimal pain has been noticed in patients under going this procedure. Anal skin tags can be removed in a simple manner using components provided with the stapling kit. We decribe a simple method of anal skin tag removal during stapled anopexy. This involves utilizing the circular anal dilator provided with the stapling kit.


Regulation of Memory Formation by the Transcription Factor XBP1.
Contextual memory formation relies on the induction of new genes in the hippocampus. A polymorphism in the promoter of the transcription factor XBP1 was identified as a risk factor for Alzheimer's disease and bipolar disorders. XBP1 is a major regulator of the unfolded protein response (UPR), mediating adaptation to endoplasmic reticulum (ER) stress. Using a phenotypic screen, we uncovered an unexpected function of XBP1 in cognition and behavior. Mice lacking XBP1 in the nervous system showed specific impairment of contextual memory formation and long-term potentiation (LTP), whereas neuronal XBP1s overexpression improved performance in memory tasks. Gene expression analysis revealed that XBP1 regulates a group of memory-related genes, highlighting brain-derived neurotrophic factor (BDNF), a key component in memory consolidation. Overexpression of BDNF in the hippocampus reversed the XBP1-deficient phenotype. Our study revealed an unanticipated function of XBP1 in cognitive processes that is apparently unrelated to its role in ER stress.


A personal sixty-year tour of genetics and medicine.
The past 60 years surely constitute a Golden Age for biomedical science, and for medical genetics in particular. A personal experience began with an encounter with inborn errors of metabolism, selection, and the incidences of hereditary diseases, and peaked with molecular biology, virology, and cytogenetics, finally focusing all three on the problem of cancer.


Minimally invasive dentistry: paradigm shifts in preparation design.
While the concept of minimally invasive dentistry has long been considered a rational, viable approach to restorative care, preparation design, material science, and long-term evidentiary support have only recently begun to provide the foundation necessary to support such treatment in the everyday practice. This article reviews the fundamental paradigm shift evidenced in contemporary prosthodontics as required to facilitate the emerging interest in delivering conservative restorative alternatives.


Methodological aspects of assessment and treatment in alcoholism.
Alcoholism is a complex concept which includes three main components: alcohol, individual and environment. That is why treatment evaluation is so difficult to assess. A bio-psycho-social approach has to be taken into account.


The necessity to develop drugs against parasitic diseases.
This review focuses on the most significant trends in the development of drugs for the treatment of malaria, African sleeping sickness and toxoplasmosis. In the case of malaria, those include new fixed-dose artemisinin combinations, antifolates and new targets in the apicoplast of Plasmodium falciparum. Targets in the treatment of trypanosomiasis are the biosynthesis of glycosylphosphatidylinositol and enzymes involved in the biosynthesis of trypanothione. Efforts to develop a vaccine against toxoplasmosis are discussed as well.


[Determination of dicofol residue in tea by wide-bore capillary gas chromatographic column].
Dicofol residue is harmful to health. More and more countries have established the limitation of dicofol in foods. This paper describes an efficient method of determination for the dicofol residue in tea. The dicofol was extracted from the tea sample with 20% acetone-hexane, cleaned up on a column of Florisil and acidic siliceous earth (sulfuric acid 0.3 mL/g) in series. Then the column was washed with 10 mL, 20% dichloromethane-hexane, the flow rate was 1 mL/min. At last dicofol was hydrolyzed with potassium hydroxide solution, forming p,p'-dichlorobenzophenone(DBP), which was separated from other ingredients through wide-bore capillary(LZ-II, 25 m x 0.53 mm i.d.) and determinated by gas chromatography with electron capture detector(ECD), using Aldrin as internal standard. When the mass ratio of dicofol was in the range of 0.05-3.0 mg/kg, the recoveries were 78%-104% and the limit of determination was 0.5 microgram/kg. This method is simple, sensitive and suitable for pesticide residue analysis. It can also be applied to the determination of dicofol residues in other plant samples such as vegetables, fruits and so on.


Dopamine agonists both stimulate and inhibit prolactin release in GH4ZR7 cells.
Prolactin secretion from the anterior pituitary gland is regulated by multiple factors including prolactin-release inhibiting factors (PIFs) and prolactin releasing factors. PIFs, however, usually dominate to exert a tonic inhibition in the biological system, and the physiological PIF is believed to be dopamine. However, there is accumulating evidence that dopamine can not only inhibit but also stimulate prolactin release. Many investigators believe that this is achieved by activating inhibitory and stimulatory subtypes of dopamine receptors. We tried to demonstrate that one subtype of dopamine receptors is capable of both inhibiting or stimulating prolactin release using GH(4)ZR(7) cells. GH(4)ZR(7) cells express only a short form of dopamine D(2) receptors (D(2s)). Low concentrations of three well-established D(2) receptor agonists (dopamine, apomorphine and bromocriptine) stimulated prolactin release from GH(4)ZR(7) cells while high concentrations inhibited the release. Haloperidol, a D(2) receptor antagonist, blocked the inhibitory action, but was unable to block the dopamine-induced stimulatory action. Pretreatment of cells with phenoxybenzamine, a receptor alkylating agent, abolished both the dopamine-induced stimulatory and inhibitory actions. Our results support the thesis that the stimulation of prolactin release induced by dopamine is mediated through dopamine D(2s) receptors since the GH(4)ZR(7) cells have only D(2s) receptors among dopamine receptors. We have concluded that the D(2s) receptor is capable of both stimulating and inhibiting prolactin release, probably via the activation of a G(s) protein by low concentrations and a G(i) protein by high concentrations of dopaminergic agents.


Phenolic aminocarboxylic acids as gallium-binding radiopharmaceuticals.
The phenolic aminocarboxylic acids ethylenediamine di [o-hydroxyphenylacetic acid] (EDDHA) and N,N'-bis [2-hydroxybenzyl] ethylenediamine N,N'-diacetic acid (HBED) form gallium complexes having high stability constants which enable them to resist exchange of gallium with plasma transferrin. 67Ga complexes were synthesized with these ligands, placing substituent groups in the phenolic ring to direct excretion via the renal or hepatobiliary route. The amount of 67Ga-Br-EDDHA excreted via the hepatobiliary route was comparable with that of some of the 99mTc agents. Excretion of 67Ga-Br-HBED was similar but with delayed transit from the liver. 67Ga COOH-EDDHA was excreted exclusively via the renal route. These findings provide a basis for developing new 67Ga or 68Ga radiopharmaceuticals, the latter for use in positron emission tomography, using these phenolic aminocarboxylates.


Evaluation of new anti-infective drugs for the treatment of syphilis. Infectious Diseases Society of America and the Food and Drug Administration.
Syphilis is caused by Treponema pallidum, a spirochetal bacterium pathogenic only for humans. The clinical course of disease is divided into three stages interspersed by periods of latency. Penicillin remains the treatment of choice for all stages of infection; tetracycline or erythromycin may be used as therapeutic alternatives in defined circumstances. Patients enrolled in clinical trials should be evaluated clinically, microscopically, and serologically for the presence of the spirochete. All participants, after undergoing counseling and giving informed consent, should be tested for infection with human immunodeficiency virus. Specific criteria exist for diagnosis of syphilis and response to therapy. It may be desirable to perform a small, uncontrolled, open trial of a new anti-infective drug for the collection of preliminary evidence of efficacy. A larger-scale, randomized, active-control comparative clinical trial is necessary to prove efficacy.


Simple cyst of the testis.
We report 5 cases of simple cyst of the testis, the largest series to date, and review the literature. Included are 2 autopsy cases, a case of a multilocular simple cyst and 1 case treated nonoperatively. Based on our experience, simple cyst of the testis should be suspected particularly in an enlarged but otherwise palpably normal testis. High resolution real-time scrotal sonography revealing an anechoic mass in the testis with well defined walls, and enhanced posterior through transmission and edge shadowing is diagnostic for a simple cyst. An asymptomatic simple cyst of the testis may be treated with observation alone. The symptomatic simple cyst should be treated ideally with local parenchyma-sparing excision.


Oncologic aspects of vermilionectomy in microinvasive squamous cell carcinoma of the lower lip.
Twelve patients with microinvasive squamous cell carcinoma of the lower lip were studied in order to determine whether vermilionectomy was justifiable. The maximum tumor thickness (MTT) varied between 1.1 and 3.1 mm. In none of the patients was there local recurrence during a mean follow-up period of 4.4 years (range 4-8). In view of these results and of what has been reported in the literature, it seems warranted to conclude that vermilionectomy is an appropriate procedure in microinvasive carcinoma of the lower lip with a MTT of up to 3 mm.


A computational prediction of structure and function of novel homologue of Arabidopsis thaliana Vps51/Vps67 subunit in Corchorus olitorius.
Vps mediated vesicular transport is important for transferring macromolecules trapped inside a vesicle. Although highly abundant, Vps shows tremendous sequence variation among diverse array of species. However, this difference in sequence, which seems to also translate into substantial functional variation, is hardly characterized in Corchorus spp. Here, our computational study investigates structural and functional features of one of the Vps subunit namely Vps51/Vps67 in C. olitorius. Broad scale structural characterization revealed novel information about the overall Vps structure and binding sites. Moreover, functional analyses indicate interaction partners which were unexplored to date. Since membrane trafficking is essentially associated with nutrient uptake and chemical de-toxification, characterization of the Vps subunit can well provide us with better insight into important agronomic traits such as stress response, immune response and phytoremediation capacity.


Body composition in late preterm infants in the first 10 days of life and at full term.
To investigate changes in body weight, fat-free mass, fat mass and percentage of body fat during early life and at full-term postconceptional age (PCA) in preterm infants born after 32 gestational weeks and before 37. Twenty-nine late preterm infants underwent growth and body composition assessment by air displacement plethysmography (ADP) at the age of 4 days and at full-term PCA. In 25 of these infants, body composition was assessed three times between days four and nine of life. The preterm infants were compared with 29 full-term infants, matched for gestational age, sex and body weight. There was a significant increase in birth weight and fat-free mass between days four and nine of life. Preterm infants had significantly more body fat 382 ± 180 g vs 287 ± 160 g than full-term infants at full-term PCA. Preterm infants showed poor linear growth between birth and full-term PCA. Weight gain after the initial postnatal weight loss consists of gain in fat-free mass. At full-term PCA, preterm infants were stunted. When compared with full-term new born infants matched for body weight and gestational age, preterm infants had more body fat and a higher percentage of body fat.


[Liver dystrophy in disseminated herpes simplex infection in pregnancy].
The reported case of an unsuccessful treatment with acyclovir of herpes simplex virus hepatitis in a young patient, during pregnancy, demonstrates the necessity of an early diagnosis with the consequence of an early therapy. If serum antibodies are not evident, the presumptive diagnosis is based upon the histological demonstration of inclusion bodies in liver biopsy specimens. With the DNA-in-situ hybridisation technique, differentiation of the type of virus infection is possible in a short time. Hence, consideration should be taken that a biopsy of the liver should be done before the coagulation system breaks down due to hepatic necrosis. The risk of the liver biopsy seems to be low compared with the high morbidity and mortality of mother and child in systemic herpes simplex virus hepatitis.


Pharmacokinetics and pharmacokinetic/pharmacodynamic relationships for angiotensin-converting enzyme inhibitors.
The pharmacokinetic (PK) properties and the pharmacokinetic/pharmacodynamic (PK/PD) relationships for the angiotensin-converting enzyme (ACE) inhibitors (ACEIs), such as enalaprilat, benazeprilat, imidaprilat and ramiprilat, differ from those of conventional drugs. This is because of their immediate and saturable binding to an ACE pool which is partly circulating (and contributing to the measured plasma concentration), and partly noncirculating (tissular), being anchored to the endothelium of vessels and not measurable by the analytical technique. A physiologically based model is required to allow appropriate interpretation of the different phases of the disposition curve of ACEI. The protracted terminal phase observed for all ACEIs is not a conventional elimination phase but a phase dependent on ACEI dissociation from ACE. In contrast, the phase which reflects ACEI elimination (and which is interpreted as a distribution phase for a conventional drug) has a short half-life, thus explaining the absence of drug accumulation during repeated dosing and mild kidney failure. ACE inhibition is the surrogate endpoint generally selected for establishing a PK/PD relationship and for simulating dosage regimen scenarios in order to decide on the appropriate dosage regimen for ACEIs.


An intervention to preschool children for reducing screen time: a randomized controlled trial.
Screen time, defined as time spent watching television, DVDs, or videos or playing computer or video games, has been related to serious health consequences in children, such as impaired language acquisition, violent behaviour, tobacco smoking and obesity. Our aim was to determine if a simple intervention aimed at preschool-aged children, applied at the health maintenance visits, in the primary care setting, would be effective in reducing screen time. We used a two group randomized controlled trial design. Two- to 6-year-old children and their parents were randomly assigned to receive an intervention to reduce their screen time, BMI and parental report of aggressive behaviour. At the end of the intervention we made home visits at 2, 6 and 9 months and the parents completed questionnaire. Parents in the intervention group reported less screen time and less aggressive behaviour than those in the control group but there were no differences in BMI z scores. This study shows that a preschool-based intervention can lead to reductions in young children's television/video viewing.


EPR, IR and electronic spectral studies on Mn(II), Co(II), Ni(II) and Cu(II) complexes with a new 22-membered azamacrocyclic [N4] ligand.
The complexes of transition metal ions with an azamacrocyclic tetradentate nitrogen donor [N4] ligand viz. 2,6,12,16,21,22-hexaaza;3,5,13,15-tetramethyltricyclo[15.3.1.1(7-11)] docosa;1(21),2,5,7,9,11(22),12,15,17,19-decaene (L) have been synthesized. All the complexes were found to have general composition M(L)X2 [where M = manganese(II), cobalt(II), nickel(II) and copper(II) and X = Cl- & NO3-]. All the complexes are characterized by the elemental analysis, molar conductance measurements, magnetic susceptibility measurements, mass, 1H NMR, IR, electronic, EPR spectral and cyclic voltammetric studies. An octahedral geometry was assigned for Mn(II), Co(II) and Ni(II) complexes and tetragonal for Cu(II) complexes. The biological actions of the ligand and complexes have been screened in vitro against many bacteria and pathogenic fungi to study their comparative capacity to inhibit the growth.


Lithium incorporation in the fibroblasts of manic-depressives.
Lithium incorporation in cultured human skin fibroblasts was measured in a group of 10 manic-depressives and 10 controls. This system was believed to eliminate many of the sources of variability to which measurement of the lithium ratio in erythrocytes (RBCs) is subject. A fibroblast lithium ratio calculated from 1-hr lithium incorporation studies correlated highly with an in vitro RBC lithium ratio in medication-free controls. Manic-depressives and controls did not differ in lithium incorporation or fibroblast lithium ratio, leading to the conclusion that the lithium ratio is probably not a good measure for differentiating the two populations.


Prostaglandin E1 reduces the frequency of rejection after heart transplantation.
This retrospective study was carried out to evaluate the effect of prostaglandin E1 on the frequency of rejection in 36 heart transplant recipients who survived orthotopic heart transplantation for 60 days or longer. The therapy for both groups was the same except group 1 (n = 12) was given PGE1 for 6 to 14 days. Indication for the PGE1 was right ventricular mismatch or failure. The prostaglandin administration started during the transplantation procedure. The dosage was 28 to 64 ng/kg/min and was tapered down from 14.7 to 32 ng later. No major side effects related to PGE1 have been observed. During the first 60 days after heart transplantation, in the group treated with prostaglandin, rejection grade 2 or higher was evident in 0.91 biopsies/patient versus 2.2 in nontreated patients, (p less than 0.05). A prolonged interval free from rejection (p less than 0.05) was observed in the patients treated with prostaglandin.


The last 48 hours of life: a case study of symptom control for a patient taking a Buddhist approach to dying.
Caring for a patient dying of cancer can, at times, be extremely difficult. Sarah was 39 years old when she died, survived by her husband and two children aged 6 and 4 years. During the weeks leading up to her death, Sarah held extensive discussions with family and the multidisciplinary team. Her goal was to live the remainder of her last few hours as comfortable as possible and to die a "peaceful death". Terminal care is an important phase of life, one in which individuals have the right to expect quality of care to ensure that their death occurs with dignity. Sarah practised Buddhism on a daily basis. Issues of spirituality, serenity and peacefulness in dying were very important to her to ensure a good rebirth.


Health in Mersey--an exercise in community diagnosis.
The process of producing a community diagnosis for the Mersey Region is described. Such an exercise is recommended for its potency in agenda-setting, and establishing a frame of reference for health promotion within the context of the strategy of Health For All By The Year 2000.


Relationship between development of microvilli on tumor cells and growth or metastatic potential of tumor cells.
The present study was undertaken to elucidate the ultrastructural differences between tumor cell clones with high growth or highly metastatic potential and those with low growth or weakly metastatic potential. Transmission, scanning and immuno-electron microscopy revealed a remarkable variance of surface microvilli between these two types of tumor cell clones. Greater numbers of microvilli appeared on the tumor cells which possess high growth or highly metastatic potential than on those of tumor cells with low growth or weakly metastatic potential. In contrast, gap junctions and desmosomes were more occasionally seen on the weakly metastatic tumor cells than the highly metastatic tumor cells. Immuno-electron microscopy revealed that epidermal growth factor (EGF) receptor and c-neu oncogene product, which is closely related to the EGF-receptor, were positively stained on the microvilli of tumor cells with high growth potential, whereas the tumor cells with low growth potential showed almost no staining. Western blot analysis also revealed that in the tumor cells with high growth potential, positive expression of c-neu at 185 kDa was stronger than in the tumor cells with low growth potential. The findings suggest that increased numbers of microvilli are closely related to the growth and metastatic potential of tumor cells.


Optimization of staining conditions for microalgae with three lipophilic dyes to reduce precipitation and fluorescence variability.
When the fluorescence signal of a dye is being quantified, the staining protocol is an important factor in ensuring accuracy and reproducibility. Increasingly, lipophilic dyes are being used to quantify cellular lipids in microalgae. However, there is little discussion about the sensitivity of these dyes to staining conditions. To address this, microalgae were stained with either the lipophilic dyes often used for lipid quantification (Nile Red and BODIPY) or a lipophilic dye commonly used to stain neuronal cell membranes (DiO), and fluorescence was measured using flow cytometry. The concentration of the cells being stained was found not to affect the fluorescence. Conversely, the concentration of dye significantly affected the fluorescence intensity from either insufficient saturation of the cellular lipids or formation of dye precipitate. Precipitates of all three dyes were detected as events by flow cytometry and fluoresced at a similar intensity as the chlorophyll in the microalgae. Prevention of precipitate formation is, therefore, critical to ensure accurate fluorescence measurement with these dyes. It was also observed that the presence of organic solvents, such as acetone and dimethyl sulfoxide (DMSO), were not required to increase penetration of the dyes into cells and that the presence of these solvents resulted in increased cellular debris. Thus, staining conditions affected the fluorescence of all three lipophilic dyes, but Nile Red was found to have a stable fluorescence intensity that was unaffected by the broadest range of conditions and could be correlated to cellular lipid content.


Technical standards for tracheal tubes.
To provide an appropriate context for understanding the standards for tracheal tubes, this article first summarizes some of the historical highlights leading to the development of present-day tracheal tubes. It also describes the current manufacturing guidelines for tracheal tubes and the rationale for these standards.


Frying performance of palm-based solid frying shortening.
In order to evaluate the frying performance of palm-based solid frying shortening against standard olein, the fresh potato chips were fried in both frying media using an open fryer. After frying the chips for 40 h in an open batch fryer, it was found that the frying quality of palm-based solid frying shortening was better than standard palm olein in terms of Free Fatty Acid (FFA) values, Total Polar Content (TPC) and Total Polymeric Material (TPM). Solid shortening gave FFA, TPC and TPM values of 0.7, 15.3 and 2.67%, respectively, whilst standard palm olein gave values for FFA, TPC and TPM of 1.2, 19.6 and 3.10%, respectively. In terms of sensory mean scores, sensory panelists preferred the color of potato chips fried in solid shortening on the first day of frying, while on the third and fifth day of frying there were no significant differences (p < 0.05) in the sensory scores of fried products in both frying mediums. However, on the fifth day of frying, panelists gave higher scores in terms of taste, flavor and crispness for potato chips fried in solid shortening. These findings show that the palm-based solid shortening is better than palm olein when used for deep fat frying in terms of FFA values, total polar content and total polymeric material, especially for starch-based products such as potato chips. The result also shows that, in terms of sensory mean scores, after frying for 40 h, the sensory panelists gave higher scores in terms of taste, flavor and crispiness for potato chips fried in palm-based solid shortening.


Percutaneous endoscopic gastrostomy: nine years experience in a tertiary care centre in Pakistan.
To review the experience of percutaneous endoscopic gastrostomy (PEG) tube placement and its management in the last nine years, at a tertiary care center in Pakistan. All patients who underwent percutaneous endoscopic gastrostomy from January 1995 to January 2004 at Shifa International Hospital, Islamabad, were included in this study. The indications, technique, complications and follow up were reviewed. A total of 182 persons underwent this procedure. There were 118 (65.0%) males and 64 (35.0%) females. Age ranged from 55-86 years. One hundred seventy five (96.0%) patients had cerebro-vascular accident, five (2.75%) had Parkinson's disease and two (1.25%) malignancy. More than 99% procedures were successful and no procedure related mortality was noted. Mild PEG site infections were encountered in eighteen (9.8%) patients which were manageable with local treatment and oral antibiotics. Four (2.2%) patients had severe tube site infection and needed parenteral antibiotics. Tube dislodgement took place in five (2.75%) patients and had to be removed and reinserted. Thirty days follow up was uneventful with regard to the tube. Longest follow up was 736 days. Percutaneous endoscopic gastrostomy had proved a viable means of enteral nutrition in patients with neurological impairment. Complications were insignificant. However, patient and care giver's education could be improved for more effective tube management, and prevention of PEG insertion site infection.


Publisher Correction: Materials challenges for the Starshot lightsail.
In the version of this Perspective originally published, the titles of the references were missing; all versions have now been amended to include them.


Evidence of pitch processing in the N100m component of the auditory evoked field.
The latency of the N100m component of the auditory evoked field (AEF) is sensitive to the period and spectrum of a sound. However, little attention was paid so far to the wave shape at stimulus onset, which might have biased previous results. This problem was fixed in the present study by aligning the first major peaks in the acoustic waveforms. The stimuli were harmonic tones (spectral range: 800-5000 Hz) with periods corresponding to 100, 200, 400, and 800 Hz. The frequency components were in sine, alternating or random phase. Simulations with a computational model suggest that the auditory-nerve activity is strongly affected by both the period and the relative phase of the stimulus, whereas the output of the more central pitch processor only depends on the period. Our AEF data, recorded from the right hemisphere of seven subjects, are consistent with the latter prediction: The latency of the N100m depends on the period, but not on the relative phase of the stimulus components. This suggests that the N100m reflects temporal pitch extraction, not necessarily implying that the underlying generators are directly involved in this analysis.


Combining non-invasive brain stimulation with functional magnetic resonance imaging to investigate the neural substrates of cognitive aging.
As aging population is increasing, new methodologies to apprehend and enhance the mechanisms related to optimal brain function in advancing age become urgent. This review describes how the combined use of non-invasive brain stimulation (NIBS) with functional magnetic resonance imaging (fMRI) provides novel experimental data on the putative neurophysiological mechanisms underlying inter-individual differences in cognitive status among older adults, also further illuminating our understanding of theoretical models proposed within the cognitive neuroscience of aging literature. In addition, it explores published evidence of how this combined procedure entails the capacity to modify the activity and connectivity of specific brain networks in older adults, potentially leading to improvements in cognitive function and other measures reflecting mental health status. Although additional research is needed, combining NIBS with fMRI might provide innovative understanding of how fundamental brain plasticity mechanisms operate in advancing age, a knowledge that may be eventually used to refine more individually tailored approaches to promote brain health in aged populations.


Detection of protein-protein interaction by bioluminescence resonance energy transfer from firefly luciferase to red fluorescent protein.
We describe a novel homogeneous protein-protein interaction assay based on bioluminescence resonance energy transfer (BRET) from mutant firefly luciferase to red fluorescent protein (DsRed). The association of glutathione S-transferase (GST)-luciferase and protein G-DsRed, which was driven by the addition of anti-GST antibody, was successfully monitored by BRET.


Integration of various stacking processes in carrier ampholyte-based capillary electrophoresis.
Field-enhanced sample stacking, field-enhanced sample injection as well as electrokinetic supercharging have been successfully integrated in carrier ampholyte-based capillary electrophoresis. Through the analysis of different test sample mixtures, it has been shown that the carrier ampholyte-based background electrolytes, in spite of their very low conductivity, allow efficient online preconcentration of analytes by field-amplified techniques. Sensitivity enhancement factors of the same magnitude as those usually encountered with classical conductive background electrolytes have been obtained in such carrier ampholyte-based buffers. Depending on the online preconcentration method that has been integrated, sensitivity enhancement factors between 50 and several thousands have been reached.


The impact of childhood abuse among women with assault-related PTSD receiving short-term cognitive-behavioral therapy.
This study examined the effect of child sexual or physical abuse on brief cognitive-behavioral therapy treatments with adults with posttraumatic stress disorder (PTSD). We analyzed secondary data from two randomized controlled trials (Resick, Nishith, Weaver, Astin, & Feuer, 2002; Resick et al., 2008) that included women with PTSD who did or did not have child sexual abuse (CSA) or child physical abuse (CPA) histories to determine whether childhood abuse impacted dropout rate or reduction in PTSD symptoms. In Study 1, presence, duration, or severity of CSA was not associated with dropout; however, frequency of CSA significantly predicted dropout (OR = 1.23). A significant CPA Severity × Treatment Group interaction emerged such that CPA severity was associated with greater dropout for prolonged exposure (PE; OR = 1.45), but not cognitive processing therapy (CPT; OR = 0.90). Study 2 found no differences in dropout. Study 1, comparing CPT and PE among women who experienced at least 1 rape found no differences in outcome based on childhood abuse history (rp (2) s = .000-.009). Study 2, a dismantling study of CPT with women seeking treatment for adult or child sexual or physical abuse found that for those with no childhood abuse, CPT-C, the cognitive-only version of CPT, had an advantage, whereas both forms of CPT worked best for those with higher frequency of childhood abuse; the effect size was small.


Understanding the migratory orientation program of birds: extending laboratory studies to study free-flying migrants in a natural setting.
For many years, orientation in migratory birds has primarily been studied in the laboratory. Although a laboratory-based setting enables greater control over environmental cues, the laboratory-based findings must be confirmed in the wild in free-flying birds to be able to fully understand how birds orient during migration. Despite the difficulties associated with following free-flying birds over long distances, a number of possibilities currently exist for tracking the long distance, sometimes even globe-spanning, journeys undertaken by migrating birds. Birds fitted with radio transmitters can either be located from the ground or from aircraft (conventional tracking), or from space. Alternatively, positional information obtained by onboard equipment (e.g., GPS units) can be transmitted to receivers in space. Use of these tracking methods has provided a wealth of information on migratory behaviors that are otherwise very difficult to study. Here, we focus on the progress in understanding certain components of the migration-orientation system. Comparably exciting results can be expected in the future from tracking free-flying migrants in the wild. Use of orientation cues has been studied in migrating raptors (satellite telemetry) and thrushes (conventional telemetry), highlighting that findings in the natural setting may not always be as expected on the basis of cage-experiments. Furthermore, field tracking methods combined with experimental approaches have finally allowed for an extension of the paradigmatic displacement experiments performed by Perdeck in 1958 on the short-distance, social migrant, the starling, to long-distance migrating storks and long-distance, non-socially migrating passerines. Results from these studies provide fundamental insights into the nature of the migratory orientation system that enables experienced birds to navigate and guide inexperienced, young birds to their species-specific winter grounds.


Estimation of the collective ionizing dose in the Portuguese population for the years 2011 and 2012, due to nuclear medicine exams.
In 2009-2010 a Portuguese consortium was created to implement the methodologies proposed by the Dose Datamed II (DDM2) project, aiming to collect data from diagnostic X-ray and nuclear medicine (NM) procedures, in order to determine the most frequently prescribed exams and the associated ionizing radiation doses for the Portuguese population. The current study is the continuation of this work, although it focuses only on NM exams for the years 2011 and 2012. The annual frequency of each of the 28 selected NM exams and the average administered activity per procedure was obtained by means of a nationwide survey sent to the 35 NM centres in Portugal. The results show a reduction of the number of cardiac exams performed in the last two years compared with 2010, leading to a reduction of the annual average effective dose of Portuguese population due to NM exams from 0.08 mSv ± 0.017 mSv/caput to 0.059 ± 0.011 mSv/caput in 2011 and 0.054 ± 0.011 mSv/caput in 2012. Portuguese total annual average collective effective dose due to medical procedures was estimated to be 625.6 ± 110.9 manSv in 2011 and 565.1 ± 117.3 manSv in 2012, a reduction in comparison with 2010 (840.3 ± 183.8 manSv). The most frequent exams and the ones that contributed the most for total population dose were the cardiac and bone exams, although a decrease observed in 2011 and in 2012 was verified. The authors intend to perform this study periodically to identify trends in the annual Portuguese average effective dose and to help to raise awareness about the potential dose optimization.


Randomised trials in surgery: the burden of evidence.
A randomised controlled trial (RCT) is considered the hierarchical peak of evidence-based medicine and a general demand for any result to be evaluated by RCTs has evolved. Yet, many advances in operative surgery do not result from RCTs and many controversies remain without an RCT being conducted. A randomised comparison of laparoscopic versus open liver resection has recently been called for. Using such a trial and others as examples, we examine the limitations of randomised design in skill-dependant interventions. Surgical procedures are skill-dependant, constantly developing, irreversible and traumatising. Additionally, placebo control is usually unethical and adequate blinding difficult or impossible to accomplish. Under these circumstances, surgeon and patient participation will be problematic and the resulting data will tend to have low external validity. While some of these obstacles can be modified, others will remain. Nonrandomised, prospective cohort comparison has other weaknesses, but may add complementary data with good external validity. An alternative hierarchy of evidence is warranted in this field.


Exogenous melatonin: morphology and kallikrein activity of male Syrian hamster submandibular gland.
Seven weeks of daily melatonin administration resulted in substantial reduction of convoluted duct cell granule population and kallikrein activity. Some reduction of intercalated duct cell granules was also observed. Testes weight and size was also dramatically reduced. All these changes were not observed after three weeks of melatonin injection.


Training in Morse code enhances involuntary attentional switching to acoustic frequency: Evidence from ERPs.
This study examined the possibility that learning Morse code could result in cortical changes in processing of physical acoustic features, as indexed by the mismatch negativity (MMN) and P3a components of the auditory event-related potential (ERP). ERPs were recorded in 9 subjects who were learning Morse code. The subjects were presented with auditory stimuli at 3 different times relative to their training (before, during and after). These stimuli were presented within an auditory 'oddball' paradigm, with repetitive standard stimuli interspersed by one of three infrequent deviant stimuli (duration, frequency or SOA). The data showed that there was a significant increase in the P3a only for frequency deviants as a function of training, whereas the MMN response was not affected by the training. These data are interpreted in terms of an attentional switching to unfamiliar changes that participants would not expect among the signals that they would grow to anticipate while receiving Morse code.


Histological alterations in tryptophan-deficient rainbow trout.
Tryptophan-deficient and nondeficient synthetic amino acid test diets were prepared using D, L-amino acids. The diets were fed to three groups of rainbow trout (Salmo gairdneri) for 8 weeks. Experimental control fish fed well and grew from 1.3 to 2.5 g. Deficient fish fed poorly and did not gain weight. Scoliosis was observed in the deficient fish after 1 week of feeding. Daily transitory scoliosis was noted in some fish. Histological studies of trypthophan-deficient scoliotic fish revealed hyperemia, disorganization of myomere septa, and protrusions of the fibrous matrix sheath, which invests the notochord. Abnormal deposition of calcium was noted in the kidney and the bony plates surrounding the notochord and sheath. Fish with mechanically induced scoliosis had disorganization of myomere septa, but did not have protrusions of fibrous matrix sheath, nor did they have abnormal calcium deposition in bone or kidney. Scoliotic fish returned to normal within 1 week upon replacement of tryptophan in the ration.


The criterion-referenced validity of the FITNESSGRAM Trunk-Extension test.
The purpose of this study was to test utility of different fitness field tests to predict self-reported low-back pain (LBP) in youth. A sample of 376 school aged (4th through 10th grade students) first completed a survey instrument designed to assess past events (and degree) of LBP. On subsequent days, participants completed a battery of different muscular fitness tests including the current FITNESSGRAM trunk extension test. Receiver operator characteristic curves (ROC) were used to test the utility of single and combined scores from various tests to predict self-reported LBP. The results show that the trunk extension test used in FITNESSGRAM has poor utility for predicting self-reported LBP. In girls, the sit-and-reach, the static curl-up test, and a composite score using static and dynamic curl-up scores had the highest Area Under the Curve (AUC=0.80, 0.71, and 0.79, respectively). Sensitivity (Se) values ranged from 75.0-85.7 while Specificity (Sp) ranged from 59.1-81.4. In boys, the dynamic curl-up test alone was the best predictor of LBP in high-school boys (AUC=0.75, Sensitivity=75.0 and Specificity=74.1). The reasonable Sensitivity values from the ROC analyses indicate that individual and aggregate indicators of musculoskeletal fitness can potentially identify girls that had LBP in the past. However, the low values for Specificity indicates that girls with "No LBP" can be misclassified as being at risk for LBP. The current FITNESSGRAM trunk extension test was not able to discriminate between students with and without LBP therefore, the utility of this test for fitness assessment in youth should be revisited.


Substrate (un)specificity of Arabidopsis NRT1/PTR FAMILY (NPF) proteins.
The conventional approach to categorizing transporters has been to class them according to their sequence homology, defining a 'family' (or a 'superfamily' if they are numerous), and according to their substrate specificity or selectivity. This general view is still relevant for some transporters, but it is being increasingly challenged. Here, we take the NRT1/PTR FAMILY (NPF) as one such example. NPF members do indeed display sequence and structural homologies with peptide transporter (PTR) proteins involved in the uptake of di- and tri-peptides in most other organisms. And in plants they were initially characterized as nitrate or peptide transporters. However, in recent years several other substrates have been identified, namely nitrite, chloride, glucosinolates, auxin (IAA), abscisic acid (ABA), jasmonates (JAs), and gibberellins (GAs). Some of these transporters are even capable of transporting more than one different substrate (e.g. nitrate/auxin, nitrate/ABA, nitrate/glucosinolates, or GA/JA). In this review, we give an overview of the substrate-specificity of the Arabidopsis NPF.


Developing a visualized patient-centered, flow-based and objective-oriented care path of cardiac catheterization examination.
It has been known that visualization is a user-preferred and more meaningful interface of information systems. To reduce the anxiety and uncertainty of patients, we transformed the sophisticated process of cardiac catheterization into visualized information. The Microsoft Visio 2003 and Excel 2003 with the VBA automation tool were used to design a process flow of Cardiac Catheterization. The results show the technical feasibility and potentials helpful for patient to realize the nursing process of cardiac catheterization.


Linkage and association analysis of candidate genes in rheumatoid arthritis.
To test for linkage and association to rheumatoid arthritis (RA) in multiplex families for polymorphic markers in candidate gene loci. Loci including the cytokine cluster on 5q31.1 and IL10, both previously investigated in RA, were included along with several other genes including ICAM-1, cMYC, the cytokine cluster on 17q11.2 and IL1RA. One hundred eighty-five multiplex RA families were genotyped for 11 microsatellite markers close to candidate genes. Markers showing evidence of linkage and/or association to RA were tested in a further cohort of families (n = 99). A single microsatellite marker in the GSTM4 gene showed some evidence of linkage, LOD 1.6 (p = 0.006). However, there was no evidence of excess allele sharing in the second cohort of families tested. There was also evidence of association to RA, using the transmission disequilibrium test for a dinucleotide repeat in the IRF gene in the cytokine cluster on 5q31.1; this was not replicated in a second cohort of families. Our results do not provide evidence of a role for these genes in RA susceptibility.


Plasma human hepatocyte growth factor concentrations in patients with biliary obstruction.
It has been suggested that human hepatocyte growth factor (hHGF) maintains the growth and viability of hepatocytes and biliary epithelial cells. The purpose of this study was to determine plasma hHGF concentrations in patients with obstructive jaundice and to correlate these findings with clinical outcome. The study included 22 patients who had biliary obstruction and underwent percutaneous transhepatic biliary drainage. The plasma concentrations of hHGF, standard liver function tests, daily bile flow and the half-life of serum total bilirubin were measured following the drainage. Plasma hHGF concentrations were significantly higher in patients with biliary obstruction compared with a control group (P<0.01). The plasma hHGF concentrations correlated with white cell count, prothrombin time and bilirubin half-life (P<0.05), but not with the values from other liver function tests. Seven patients who died within 3 months after biliary drainage had significantly higher concentrations of plasma hHGF than the 15 patients who survived for at least 3 months (P<0.05). The patients who experienced a poor outcome also had lower bile flows and prolonged bilirubin half-lives compared with the survivors (P<0.05). The plasma hHGF concentrations decreased significantly after biliary drainage in the survivors (P<0.01), but not in the patients with a poor outcome. These results suggest that systemic inflammation and the hepatic dysfunction caused by obstructive jaundice cause an increase in the plasma concentrations of hHGF. In addition, the plasma concentrations of hHGF may be a predictor of poor outcome in jaundiced patients.


Berberine derivative, Q8, stimulates osteogenic differentiation.
Berberine has been implicated to be involved in maintaining bone health due to its anti-oxidative and osteogenic properties. However, low potency and low bioavailability limit the clinical development of the drug. To overcome these obstacles, we previously synthesized a compound, Q8, which is a structural homolog of berberine. The present study examined the pharmacological functions of Q8 to evaluate its potential use in bone regeneration with respect to osteoblast differentiation. Here, we report that Q8 enhanced BMP4-induced alkaline phosphatase (ALP) activity and transcription from the ALP promoter. In addition, Q8 suppressed the expression and activity of PPARγ (a known negative regulator of osteogenesis due to its stimulatory effects on adipogenesis and its role as an adipogenic transcription factor), which in turn increases β-catenin expression in the nucleus, and ultimately promotes osteoblast differentiation. Meanwhile, Q8 reversed the inhibitory effects of the PPARγ agonist, rosiglitazone, on osteoblast differentiation. This study demonstrated that Q8 promotes osteoblast differentiation via inhibition of PPARγ and the enhancement of osteoblast function by Q8 may contribute to the prevention for osteoporosis.


Relationship of megakaryocyte size at diagnosis to chemotherapeutic response in children with acute nonlymphocytic leukemia.
Small megakaryocytes are frequently seen in patients with acute nonlymphocytic leukemia (ANLL). In this study, median megakaryocyte diameters were determined in marrow biopsy specimens of 32 children at diagnosis of ANLL and related to platelet count and chemotherapeutic response. The association between median megakaryocyte size and time-to-failure was striking. Seven of 9 patients with median megakaryocyte diameters greater than 20 microns remain in continuous complete remission for more than 3 yr, whereas 20 of 23 patients with smaller median megakaryocyte diameters failed therapy within 15 mo (p = 0.002). By Cox-regression analysis, megakaryocyte size had independent prognostic value (p less than 0.001), surpassing that of spleen size, the only other feature having significant association with time-to-failure. Megakaryocyte size at diagnosis may be useful for predicting the likelihood of prolonged complete remission in ANLL.


Attenuation correction of thallium SPECT using differential attenuation of thallium photons.
The greatest limitation of 201Tl for the diagnosis of coronary artery disease remains the high soft-tissue attenuation of its low energy photons. However, thallium also emits a smaller number of higher energy photons. Since photons of higher energy undergo less attenuation, it was postulated that the amount of attenuation could be ascertained from the ratio of the low-to-high energy photon counts. A planar phantom was used to derive a regression equation relating attenuation to the count ratio of the low and high energy peaks. A three-dimensional heart phantom was constructed and SPECT images were obtained in air and water. Application of the attenuation correction algorithm to the SPECT images of the phantom in water produced images quantitatively similar to that obtained in air. We conclude that by using differential photon attenuation, correction of 201Tl SPECT using a single order post-processing technique is feasible. This technique may allow for more accurate analysis of thallium myocardial perfusion scintigraphy.


[Investigation of reduction of exposure dose in digital mammography: relationship between exposure dose and image processing].
In digital mammograms, granularity is an important image property for the detection of microcalcifications and masses. Therefore, we investigated the relationship between the conditions of various exposure doses and the detectability of RMI156 phantom images with and without image processing for the reduction of exposure dose. The images are processed with Gaussian filter and unsharp-masking filters to evaluate the effects on image properties by using the digital Wiener spectrum (WS) presampled modulation transfer function (MTF). In addition, observer performance tests for the detectability of microcalcifications and masses are performed. With Gaussian filtering, the WS value decreased to 50% at 2.0 cycles/mm and the detectability score of masses increased 80% and 12%, on 1.34 mGy and 2.62 mGy, respectively (p<0.05). With unsharp-masking (7 x 7 pixels), the MTF value increased to 126% at 2.0 cycles/mm, and the detectability of microcalcification to 32% and 5%, on 1.34 mGy and 5.28 mGy, respectively (p<0.05) compared with the original image. The optimal dose of simulated lesions with unsharp masking became 5.25 mGy. The unsharp masking could reduce 37% of the exposure dose without a loss of detectability of microcalcifications and masses.


Smart Starch-Poly( N-isopropylacrylamide) Hybrid Microgels: Synthesis, Structure, and Swelling Behavior.
In this study, we present hybrid microgels made of starch nanoparticles (SNPs) and poly( N-isopropylacrylamide) [p(NIPAM)]. SNPs were formed through nanoprecipitation. Hybrid microgels were prepared by surfactant-free precipitation polymerization (SFPP) or in the presence of surfactant precipitation polymerization (PP) at different NIPAM/SNP ratios. Dynamic light scattering results of hybrid microgels synthesized by SFPP revealed changes in volume phase transition temperature according to SNP amount, where the increase in the hydrophilic content caused small shifts in the lower critical solution temperature (LCST), reaching nearly 35 °C. Colloidal stability was improved with the SNP content, leading to increased stability because of the hydroxyl groups. Small-angle X-ray scattering indicates a core-shell structure above the LCST, where SNPs chains cover a p(NIPAM) core. Swelling curves experimentally obtained were analyzed using the Flory-Rehner model, where the interaction parameter (χ) has been modeled either by a series expansion of the swelling ratio or by a Hill-like equation for a cooperative thermotropic transition.


Direct detection of Campylobacter jejuni in chicken cecal contents by PCR.
Campylobacter jejuni in chicken feces was detected by PCR and Southern blot hybridization (SBH). The detection limits of C. jejuni in chicken feces were 34,000 cells by PCR and 340 cells by SBH. Some cecal contents of chickens up to 3 weeks old were C. jejuni positive by SBH whereas all of them were negative by PCR. Two of 51 cecal contents of 18-day-old chicken embryos were C. jejuni positive by PCR and SBH; but, C. jejuni were not isolated from the samples by conventional culture with selective enrichment.


Isomerization of herpes simplex virus 1 genome: identification of the cis-acting and recombination sites within the domain of the a sequence.
Previous studies have shown that the a sequence located at the termini and at the junction between the L and S components is the site-specific, cis-acting sequence mediating the inversions of herpes simplex virus 1 DNA. We constructed mutated a sequences, inserted them into the thymidine kinase gene, and recombined them into the L component of the viral genome. Deletion of Uc or Ub domains of the a sequence did not affect inversions, whereas the deletion of direct repeat #4 (DR4) drastically reduced their frequency. Deletion of both direct repeat #2 (DR2) and DR4 abolished inversions. Recombinational events leading to inversions appear to occur through DR2, and possibly DR4. These results complement previous studies showing that most of one DR1 sequence can also be dispensed with and are consistent with the hypothesis that DR4 and possibly DR2 are the cis-acting sites for the inversions mediated by the a sequence.


Expression of Stromal Caveolin- 1 May Be a Predictor for Aggressive Behaviour of Breast Cancer.
Caveolin-1 (Cav-1) is well known as a principal scaffolding protein of caveolae which are specialized plasma membrane structures. The role of Cav-1 in tumorigenesis of breast cancers is relatively less studied. The aim of the present study is to describe the biological roles of Cav-1 in breast cancers considering its contrasting dual functions as an oncogene and as a tumor suppressor. This study included 71 females with breast cancer who had been histopathologically diagnosed in Private Gunes Pathology Laboratory between the years 2007, and 2012. The mean age is 52.48 ± 12.8 years. Patients were followed up for a mean period of 47.97 ± 20.48 months. We didn't determine Cav-1 positive tumor cells. In 36 cases (50.7%), there were stromal expressions of Cav-1. In the statistical analysis, there was a statistically significant correlation between Cav-1 expression and ER (p = 0.033), metastasis (p = 0.005), lymphatic invasion (p = 0.000), nodal metastasis (p = 0,003), perinodal invasion (p = 0.003), metastasis (p = 0.005) and survival (p = 0.009). We found that Cav-1 expression is associated with tumor size, histological grade, lymph node involvement. Accordingly, we have suggested that Cav-1 may be a predictive biomarker for breast cancer.


Ultrasound perfusion imaging of small stroke involving the thalamus.
Ultrasound (US) perfusion imaging of ischemic stroke has mainly been applied to large middle cerebral artery infarction. We investigated whether small stroke involving the thalamus can also be detected. Phase inversion harmonic imaging (PIHI) was applied to patients with small infarctions involving the thalamus (maximal longitudinal infarct diameter less than 3 cm). PIHI was performed from both the left and right side in axial diencephalic planes. Infarct size and location as well as perfusion properties (MTT maps) were known from MRI. US perfusion parameters were derived from the signal enhancement time course (bolus kinetics, SonoVue for peak-signal increase and time-to-peak. Seventeen patients (52 +/- 11 years, 24% female) with 18 strokes (16 unilateral, 1 bilateral) were included. Six US examinations (18%) were inadequate for analysis due to an insufficient transtemporal bone window. US perfusion depicted 90 % of infarcts with a longitudinal diameter of more than 2 cm. Infarcts with a longitudinal diameter of less than 2 cm were hardly identified. PIHI allows identification of a small infarction involving the thalamus subject to infarct size.


[Helicobacter spp. infections in chronic liver damage].
Liver is a key organ responsible for organism’s homeostasis. A proper function of this organ is crucial for detoxification of metabolic products and regulation of metabolic processes of macromolecules (proteins, lipids, carbohydrates). The most important infectious factors, leading to liver damage, are primary hepatotropic viruses, particularly those causing chronic inflammation of the organ (HBV, HCV, HDV), which may subsequently cause cirrhosis and/or primary hepatocellular carcinoma. There has been a growing interest in Helicobacter spp. liver infections as a potential factor promoting injury of the organ towards hepatocellular carcinoma. The association between hepatocellular carcinoma and the presence of Helicobacters in the liver has been well documented in animal models (Helicobacter hepaticus versus liver cancer in mice). Some reports also indicate similar association in humans, where the presence of Helicobacter antigens in patients with liver cancer is detected more often in comparison to healthy or chronically infected population. Although the molecular mechanisms underlying such a phenomenon are not well known, the knowledge on this subject has considerably increased during recent years. The review presents data on the association between the presence of Helicobacter spp. in the liver and injuries of the organ, as well as the role that is played by the bacteria in chronic liver diseases.


Dependence- and Disability-Free Life Expectancy Across Eight Low- and Middle-Income Countries: A 10/66 Study.
The objective of this study was to estimate healthy life expectancies in eight low- and middle-income countries (LMICs), using two indicators: disability-free life expectancy (DFLE) and dependence-free life expectancy (DepFLE). Using the Sullivan method, healthy life expectancy was calculated based on the prevalence of dependence and disability from the 10/66 cohort study, which included 16,990 people aged 65 or above in China, Cuba, Dominican Republic, India, Mexico, Peru, Puerto Rico, and Venezuela, and country-specific life tables from the World Population Prospects 2017. DFLE and DepFLE declined with older age across all sites and were higher in women than men. Mexico reported the highest DFLE at age 65 for men (15.4, SE = 0.5) and women (16.5, SE = 0.4), whereas India had the lowest with (11.5, SE = 0.3) in men and women (11.7, SE = 0.4). Healthy life expectancy based on disability and dependency can be a critical indicator for aging research and policy planning in LMICs.


Fetal liver position and perinatal outcome for congenital diaphragmatic hernia.
Despite advances in postnatal care, patients born with a congenital diaphragmatic hernia (CDH) suffer substantial morbidity and mortality. The present study was undertaken to determine the prognostic influence of prenatally-diagnosed liver herniation in the hemithorax in fetuses with CDH. The medical records of 48 patients evaluated for a prenatally-diagnosed left CDH were retrospectively reviewed. Patients were analysed according to the position of the liver by prenatal ultrasound; 32 fetuses had a major portion of the liver herniated into the left hemithorax ('liver up') and 16 had an intra-abdominal liver ('liver down'). Liver position was determined using colour-flow Doppler ultrasonography. There were two fetal deaths in the liver-up group and one in the liver-down group. The liver-up group more frequently required extracorporeal membrane oxygenation (ECMO) support (53 per cent) compared with the liver-down group (19 per cent). Postnatal survival was significantly less in the liver-up group (43 per cent) vs. the liver-down group (93 per cent). Fetuses with congenital diaphragmatic hernia and liver herniated into the hemithorax have a much worse prognosis than similarly afflicted fetuses without liver herniation. Prenatal ultrasonographic diagnosis of congenital diaphragmatic hernia allows for preparation for a critically ill newborn and aids in prenatal family counselling.


Do patients who self-harm consult their general practitioner soon after hospital discharge? A cohort study.
Deliberate self-harm (DSH, attempted suicide) is one of the most common reasons for emergency hospital admission in Great Britain. Approximately 20 % of patients repeat self-harm in the 12 months after admission. The GP's role in DSH aftercare and the prevention of repeat episodes is unclear. The data were obtained from a 12-month follow-up of a series of 968 consecutive patients from 49 practices who attended an accident and emergency (A&E) department in Bristol or Bath, UK, following an episode of self-harm between 26(th) May 1997 and 1(st) March 1999. Information on consultation patterns were available for 681 (70 %) of the patients. Two hundred and fourteen (31 %) of these consulted their GP in the week following the episode, 360 (53 %) within 4 weeks. Of the subjects, 44 % were discharged directly from A & E; these patients were more likely to consult their GP in the 4 weeks after the episode. Over the 12-month follow-up, 117 (17 %) attended hospital for a repeat episode of DSH; 9 % of these repeats occurred within 1 week and 28 % within 4 weeks of the index event. Although few (2 out of 11 patients--18 %) of those repeating in the first week after the index episode consulted their GP prior to repeating, 50 % (11/22) of those who repeated in the 1-4 weeks after an episode did so. Consultation patterns indicate that most people who deliberately self-harm consult their GP soon after the episode. This consultation may provide an opportunity for preventing repeat DSH and suicide.


Infrared methods for high throughput screening of metabolites: food and medical applications.
Chemical and physiological properties are related to individual or bioactive compounds such as essential oils, terpenoids, flavonoids, volatile compounds and other chemicals which are present in natural products in low concentrations (e.g. ppm or ppb). For many years, classical separation, chromatographic and spectrometric techniques such as high performance liquid chromatography (HPLC), gas chromatography (GC), liquid chromatography (LC) and mass spectrometry (MS) have been used for the elucidation of isolated compounds from different matrices. Hence, the use of standard separation, chromatographic and spectrometric methods was found useful in chemical and both plant and animal physiology studies, for fingerprinting and comparing natural and synthetic samples, as well as to identify single active compounds. It has been generally accepted that a single analytical technique will not provide sufficient visualization of the metabolome, hence holistic techniques are needed for comprehensive analysis. In the last 40 years near infrared (NIR) spectroscopy became one of the most attractive and used methods of analyzing agricultural related products and plant materials which provide simultaneous, rapid and non-destructive quantitation of major. This technique has been reported to determine other minor compounds in plant materials such as volatile compounds and elements. The aim of this short review is to describe some recent applications of NIR spectroscopy combined with multivariate data analysis for high throughput screening of metabolites with an emphasis on food and medical applications.


Reactivity of urinary bladder smooth muscle in guinea pigs to acetylcholine and carbachol--participation of acetylcholinesterase.
The authors examined the influence of acetylcholinesterase inhibitor (neostigmine) on the in vitro reactivity of urinary bladder smooth muscle (UBSM) in guinea pigs. The aim of the present study was to determine the participation of pharmacokinetic properties of acetylcholine and carbachol in different UBSM reactivity to these mediators. In vitro method of organ baths was used and reactivity of UBSM strips to cumulative doses of acetylcholine and carbachol was tested before and after the incubation with neostigmine (10(-4) mol.l(-1)). Neostigmine caused a significant increase of UBSM reactivity to acetylcholine. The UBSM reactivity to acetylcholine was significantly higher at concentrations of 10(-5) and 10(-4) mol.l(-1) compared to carbachol at the same concentrations. These findings indicate that in addition to different mediator affinity to muscarinic receptors and to their different intrinsic activity, the pharmacokinetic properties of acetylcholine and carbachol also participate in UBSM reactivity.


Projection-type integral imaging system using multiple elemental image layers.
A projection-type integral imaging system is proposed using multiple elemental image layers obtained from a single projector. In a conventional projection-type integral imaging system, only one display mode among real, virtual, and focused modes can be displayed selectively with a single projector. Plural projectors must be used for the generation of multiple elemental image layers. However, in the proposed method, the real and the virtual modes can be displayed simultaneously by generating multiple elemental image layers within the depth of field of a single projector. To embody the proposed method, the system specifications, such as the focal lengths of lenses and the distance between components, must be designed carefully. In this paper, we define and calculate the system factors and present the design role of the system. The feasibility of the proposed method is demonstrated with experimental results.


Expression of stromelysin 1 in human astrocytoma cell lines.
In a wide variety of tumor types, the expression of stromelysin 1 which is one of the matrix metalloproteinases (MMPs) has been shown to correlate with tumor invasion. However, little is known about the distribution of stromelysin in human brain tumors. We have previously shown that a correlation exists between the type IV collagenases, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 transcripts and in vitro invasiveness among 7 human astrocytoma cell lines. In the present study, we analyzed the expression of stromelysin 1 among the same panel of human astrocytoma cell lines and human fibroblasts by northern blot analyses and in situ hybridization. Northern blot analysis demonstrated that SF-126 and U87 MG expressed high level stromelysin 1 transcripts. Following heat shock stimulation, the stromelysin 1 transcript was up-regulated in U87 MG astrocytoma cells. In situ hybridization analysis showed specific intracytoplasmic localization of mRNA for stromelysin in these astrocytoma cell lines. By casein zymography, we have determined that both SF-126 and U87 MG secreted stromelysin 1 protein. We conclude that stromelysin 1 is expressed by certain human astrocytoma cell lines, and this study confirms the importance of continuing to characterize the proteolytic enzyme profile of these tumors to fully understand the molecular mechanisms involved in astrocytoma invasiveness.


The importance of width/length ratios of maxillary anterior permanent teeth in esthetic rehabilitation.
The aim of this study was to investigate the importance of the width/length (W/L) ratio of maxillary anterior permanent teeth in anterior esthetic rehabilitation. Digital photographs were taken of the anterior teeth for each participant (approximately 20 years old). A maxillary impression was taken with irreversible hydrocolloid and cast in die stone under vacuum. The widest mesiodistal width and incisogingival length of the tested teeth were measured. The data were submitted to analysis of variance, which showed significant statistical differences within each parameter (P< .05). The width and length measurements varied between maxillary anterior teeth in the following or der: central incisors > canines > lateral incisors. Maxillary central incisors displayed the largest W/L ratio (85%), maxillary lateral incisors (LI) displayed the smallest W/L ratio (79%), and canines displayed the intermediate W/L ratio (83%). These dimensions have a positive effect on the final restoration; therefore, it is suggested that the specific width, length, and W/L ratio should be used in esthetic rehabilitations of maxillary anterior teeth.


Suppression of phorbol-12-myristate-13-acetate-induced tumor cell invasion by apigenin via the inhibition of p38 mitogen-activated protein kinase-dependent matrix metalloproteinase-9 expression.
Apigenin has special interest for the development of chemopreventive agents against cancer because it is a widely distributed plant flavonoid that has antitumor properties. In this study, we investigated the apigenin effects on the protease-mediated invasiveness in human metastatic cancer cell lines Caski, SK-Hep1, and MDA-231. We found that apigenin markedly inhibits the phorbol-12-myristate-13-acetate (PMA)-induced increase in MMP-9 expression and activity in several cancer cell lines. These effects of apigenin are dose-dependent and correlate with the suppression of MMP-9 mRNA expression levels. PMA caused about a 5-fold induction in MMP-9 promoter activity, which was also suppressed by apigenin treatment in Caski cells. We found that apigenin could inhibit PMA-induced phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), which was involved in the down-regulation of the expression of matrix metalloproteinase-9 (MMP-9) at mRNA levels. Furthermore, the treatment of inhibitors specific for p38 MAPK (SB203580) to Caski cells caused the reduction of MMP-9 expression. Restoration of p38 expression partly increased PMA-induced MMP-9 secretion blocked by apigenin treatment in Caski cells. These results showed apigenin might inhibit the invasion and migration abilities of Caski cells by reducing the MMP-9 expression through suppressing the p38 MAPK signaling pathway. These findings indicate that apigenin might be a useful strategy for controlling metastasis and the invasiveness of tumors.


A home visitation program welcomes home first-time moms and their infants.
This article describes a creative maternal and infant home visiting program for first-time parents. Two-year outcomes indicate the program improved parents' infant safety knowledge, positively affected the mother's decision to breastfeed, and promoted infant primary care visits in a cost-effective way.


Artifact-free deconvolution in light field microscopy.
The sampling patterns of the light field microscope (LFM) are highly depth-dependent, which implies non-uniform recoverable lateral resolution across depth. Moreover, reconstructions using state-of-the-art approaches suffer from strong artifacts at axial ranges, where the LFM samples the light field at a coarse rate. In this work, we analyze the sampling patterns of the LFM, and introduce a flexible light field point spread function model (LFPSF) to cope with arbitrary LFM designs. We then propose a novel aliasing-aware deconvolution scheme to address the sampling artifacts. We demonstrate the high potential of the proposed method on real experimental data.


Representational neglect and navigation in real space.
Topographical orientation relies on several cognitive strategies adopted by humans to move within the environment. In the present study, we investigate whether mental representation disorders affect specific cognitive mechanisms subserving human orientation. In order to differentiate distinct cognitive mechanisms involved in topographical orientation, we created a human version of the well-known "Morris Water Maze" and tested left and right brain damaged patients in a place-learning task. The test required the subjects to explore an experimental room in which no visual cues were present, find a target location, and then reach it in different conditions. The ability to memorize target locations in short- and long-term memory was also assessed. We found that all participants were able to reach the target location by using idiothetic cues (vestibular inputs, motor efferent copy, etc.). On the other hand, when starting position changed and re-orientation was necessary to reach the target location, in order to compute a new trajectory, only patients affected by representational neglect got lost. These results provide the first neuropsychological evidence of involvement of mental representation in a specific cognitive process allowing humans to reach a target place from any location in the environment.


[Guidelines for diagnosis and treatment of constipation in Mexico. C) Medical and surgical treatment].
There are multiple therapeutic options for the management of constipation, from lifestyle modifications to the use of laxatives and in extreme cases surgery. To establish the clinical guidelines for diagnosis and treatment of chronic constipation in Mexico we conducted a review of the literature regarding medical and surgical treatments for chronic constipation and have made recommendations based on evidence. Low water consumption, physical inactivity and low intake of fiber are conditions associated with chronic constipation, but the evidence to prove these associations is scarce. Bolus forming agents are useful in the management of constipation with normal colonic transit and defecation without dissynergia. Evidence supports the use of lactulose (IB) and polyethylene glycol (IA) as the most safe and effective agents in the long term in adults. The use of stimulant laxatives (docusate, picosulfate, senna) is recommended only for short periods. Tegaserod is an agonist of 5-HT4 receptors and there are many clinical trials supporting its effectiveness in the management of functional constipation (IA). However "their cardiovascular safety has been questioned recently. Biofeedback therapy is the gold standard in the management of constipation associated with pelvic floor dyssynergia. Surgical treatment is reserved for extreme cases of colonic inertia. The treatment of constipation should be based on the underlying pathophysiological mechanisms and the selection of drugs must be made according to the scientific evidence.


[Magnetic resonance imaging : Recent studies on biological effects of static magnetic and high‑frequency electromagnetic fields].
During the last few years, new studies on biological effects of strong static magnetic fields and on thermal effects of high-frequency electromagnetic fields used in magnetic resonance imaging (MRI) were published. Many of these studies have not yet been included in the current safety recommendations. Scientific publications since 2010 on biological effects of static and electromagnetic fields in MRI were researched and evaluated. New studies confirm older publications that have already described effects of static magnetic fields on sensory organs and the central nervous system, accompanied by sensory perceptions. A new result is the direct effect of Lorentz forces on ionic currents in the semicircular canals of the vestibular system. Recent studies of thermal effects of high-frequency electromagnetic fields were focused on the development of anatomically realistic body models and a more precise simulation of exposure scenarios. Strong static magnetic fields can cause unpleasant sensations, in particular, vertigo. In addition, they can influence the performance of the medical staff and thus potentially endanger the patient's safety. As a precaution, medical personnel should move slowly within the field gradient. High-frequency electromagnetic fields lead to an increase in the temperature of patients' tissues and organs. This should be considered especially in patients with restricted thermoregulation and in pregnant women and neonates; in these cases exposure should be kept as low as possible.


Effects of respirators on performance of physical, psychomotor and cognitive tasks.
Possible work decrements caused by respirator usage were examined. A battery of physical, psychomotor and cognitive tasks was used to investigate the effects of respirator wear on 12 subjects. A repeated measures experimental design was used to study the effects of three types of respirators: a disposable dust mask; an air purifying half-mask; and a full-face airline mask. Performance while wearing a mask was compared to the control condition without a respirator. The results from the physical work task of riding a bicycle ergometer indicated approximately a 10% increase in oxygen consumption when subjects wore half and full-face masks in comparison to when they performed the tasks without a mask. The results indicate that wearing the respirators did not have a significant effect on the performance of cognitive tasks but did affect significantly the performance of psychomotor tasks such as steadiness of work performance and movements requiring accurate control for positioning of objects.


Decisional Guidance Tool for Antibiotic Prescribing in the Skilled Nursing Facility.
To derive weighted-incidence syndromic combination antibiograms (WISCAs) in the skilled nursing facility (SNF). To compare burden of resistance between SNFs in a region and those with and without protocols designed to reduce inappropriate antibiotic use. Retrospective analysis of microbial data from a regional laboratory. We analyzed 2484 isolates collected at a regional laboratory from a large mixed urban and suburban area from January 1, 2015, to December 31, 2015. A total of 28 regional SNFs (rSNFs) and 7 in-network SNFs (iSNFs). WISCAs were derived combining Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, and reports restricted to fluoroquinolones, cefazolin, amoxicillin clavulanate, and trimethoprim/sulfamethoxazole. Pooling the target isolates into WISCAs resulted in an average of 28 of 37 achieving a number greater than 30 with an average of 50 isolates (range = 11-113; >97% urinary). Significant differences were found in antibiotic susceptibility between grouped rSNF data and iSNF data of 75% vs 65% (2.76-11.77; P = .002). The susceptibilities were higher in iSNFs with active antibiotic reduction protocols compared with iSNFs without protocols and rSNFs (effect size = .79 vs .67 and .65, respectively) (I2 = 93.33; P < .01). Susceptibilities to cefazolin (95% vs 76%; P < .001) and fluoroquinolones (72% vs 64%; P = .048) were significantly higher in iSNFs with active urinary tract infection protocols as compared with iSNFs without antibiotic reduction protocols. These results suggest that WISCAs can be developed in most SNFs, and their results can serve as indicators of successful antibiotic stewardship programs.


Diagnosis, Epidemiology, and Management of Hypertension in Children.
National guidelines for the diagnosis and management of hypertension in children have been available for nearly 40 years. Unfortunately, knowledge and recognition of the problem by clinicians remain poor. Prevalence estimates are highly variable because of differing standards, populations, and blood pressure (BP) measurement techniques. Estimates in the United States range from 0.3% to 4.5%. Risk factors for primary hypertension include overweight and obesity, male sex, older age, high sodium intake, and African American or Latino ancestry. Data relating hypertension in childhood to later cardiovascular events is currently lacking. It is known that BP in childhood is highly predictive of BP in adulthood. Compelling data about target organ damage is available, including the association of hypertension with left ventricular hypertrophy, carotid-intima media thickness, and microalbuminuria. Guidelines from both the United States and Europe include detailed recommendations for diagnosis and management. Diagnostic standards are based on clinic readings, ambulatory BP monitoring is useful in confirming diagnosis of hypertension and identifying white-coat hypertension, masked hypertension, and secondary hypertension, as well as monitoring response to therapy. Research priorities include the need for reliable prevalence estimates based on diverse populations and data about the long-term impact of childhood hypertension on cardiovascular morbidity and mortality. Priorities to improve clinical practice include more education among clinicians about diagnosis and management, clinical decision support to aid in diagnosis, and routine use of ambulatory BP monitoring to aid in diagnosis and to monitor response to treatment.


Foreseeing the future of mutualistic communities beyond collapse.
Changing conditions may lead to sudden shifts in the state of ecosystems when critical thresholds are passed. Some well-studied drivers of such transitions lead to predictable outcomes such as a turbid lake or a degraded landscape. Many ecosystems are, however, complex systems of many interacting species. While detecting upcoming transitions in such systems is challenging, predicting what comes after a critical transition is terra incognita altogether. The problem is that complex ecosystems may shift to many different, alternative states. Whether an impending transition has minor, positive or catastrophic effects is thus unclear. Some systems may, however, behave more predictably than others. The dynamics of mutualistic communities can be expected to be relatively simple, because delayed negative feedbacks leading to oscillatory or other complex dynamics are weak. Here, we address the question of whether this relative simplicity allows us to foresee a community's future state. As a case study, we use a model of a bipartite mutualistic network and show that a network's post-transition state is indicated by the way in which a system recovers from minor disturbances. Similar results obtained with a unipartite model of facilitation suggest that our results are of relevance to a wide range of mutualistic systems.


Pyro-phototronic nanogenerator based on flexible 2D ZnO/graphene heterojunction and its application in self-powered near infrared photodetector and active analog frequency modulation.
Even though 2D ZnO has been utilized for enhanced self-powered sensing by strain modulation due to its piezoelectric property, study on utilizing the pyroelectric property of ZnO remains unexplored. The piezoelectric property of 2D ZnO works on mechanical strain, which disrupts the structure of ZnO leading to the failure of the device. For a pyroelectric nanogenerator, the temperature difference can be triggered by an external light source, which does not disrupt the ZnO structure and also avoids the need for physical bending/pressing, as in the case of a piezoelectric nanogenerator. This work represents the first demonstration of the fabrication of a flexible 2D ZnO/Gr pyro-phototronic diode where the pyro-potential generated in the 2D ZnO due to the near infrared (NIR) illumination adds to or subtracts from the built-in electric field of the heterojunction and modulates the depletion region of the heterojunction thereby enabling bias-free operation. Furthermore, the variation in the depletion width of the heterojunction was utilized as a variable capacitor in the frequency modulator, wherein, with the increasing intensity, the frequency of oscillations increased from 9.8 to 10.42 MHz. The work presented provides an alternative approach for a self-powered NIR photodetector and the utilization of the same at circuit level, having potential applications in the fields of optothermal detection, electronic tuning circuits, etc.