Patient characteristics and the therapist as predictors of depressed patients' outcome expectation over time: A multilevel analysis.
Objective: Although there is an established link between patients' early positive outcome expectation for and their actual improvement from therapy, there is little research on patients' change in outcome expectation across therapy and both patient and therapist correlates of early outcome expectation level and change. The present study examined: (i) the overall trajectory of change in patients' outcome expectation through cognitive-behavioral therapy (CBT) for depression; (ii) patient characteristics as predictors of both initial outcome expectation and change in outcome expectation; and (iii) between-therapist effects in outcome expectation change. Method: Depressed patients (N = 143) received a brief course of CBT. Outcome expectation was measured at screening, pretreatment, session 7, and session 14. Results: Outcome expectation linearly increased from screening to session 14. When controlling for other patient characteristics at intake, having previous depressive episodes was negatively associated with initial outcome expectation and higher well-being was positively associated with initial outcome expectation. When controlling for early alliance and early symptom change, outcome expectation change was predicted by previous depressive episodes. Finally, therapist effects emerged in outcome expectation over time. Conclusions: Various depressed patients' characteristics predict initial outcome expectation level and change, with significant between-therapists' differences related to outcome expectation change.


Expanded microporous polytetrafluoroethylene (PTFE) grafts in contaminated wounds: experimental and clinical study.
Autogenous vein graft is regarded as an ideal arterial substitute for its long-term patency and relative resistance to infection. A clinical instance of life-threatening hemorrhage from an infected disrupted vein graft stimulated a study in dogs, comparing vein and PTFE graft performance in wounds contaminated with S. aureus and E. coli cultured from the patient's wound. Infective disruption of vein wall occurred in three of ten animals resulting in exsanguination and death. Host artery disruption at PTFE suture line occurred in one of ten animals. Thrombosis of graft and host artery in this animal precluded hemorrhage and death. This led to favorable clinical experiences with PTFE grafts in contaminated wounds of 22 trauma patients. It is concluded that PTFE is better assurance against disruption and hemorrhage than vein graft in contaminated, potentially infected sites. PTFE may be used preferentially as a vascular substitute in trauma patients provided that all traditional surgical safeguards and principles are followed.


A temporal interpolation approach for dynamic reconstruction in perfusion CT.
This article presents a dynamic CT reconstruction algorithm for objects with time dependent attenuation coefficient. Projection data acquired over several rotations are interpreted as samples of a continuous signal. Based on this idea, a temporal interpolation approach is proposed which provides the maximum temporal resolution for a given rotational speed of the CT scanner. Interpolation is performed using polynomial splines. The algorithm can be adapted to slow signals, reducing the amount of data acquired and the computational cost. A theoretical analysis of the approximations made by the algorithm is provided. In simulation studies, the temporal interpolation approach is compared with three other dynamic reconstruction algorithms based on linear regression, linear interpolation, and generalized Parker weighting. The presented algorithm exhibits the highest temporal resolution for a given sampling interval. Hence, our approach needs less input data to achieve a certain quality in the reconstruction than the other algorithms discussed or, equivalently, less x-ray exposure and computational complexity. The proposed algorithm additionally allows the possibility of using slow rotating scanners for perfusion imaging purposes.


Individual- and neighborhood-level socioeconomic status and risk of aggressive breast cancer subtypes in a pooled cohort of women from Kaiser Permanente Northern California.
Low socioeconomic status (SES) has been associated with a higher risk of aggressive breast cancer (BC) subtypes, but few studies have examined the independent effects of both neighborhood-level socioeconomic status (nSES) and individual-level SES measures. This study included 5547 women from the Pathways and Life After Cancer Epidemiology cohorts who were diagnosed with invasive BC. Generalized estimating equation models were used to examine associations of nSES (a composite score based on income, poverty, education, occupation, employment, rent, and house value) and individual-level SES (income and education) with BC subtypes: luminal B (LumB), Her2-enriched (Her2-e), and triple-negative breast cancer (TNBC) relative to luminal A (LumA). Models controlled for age, race, nativity, stage, days from diagnosis to survey, and study cohort and simultaneously for nSES and individual-level SES. In fully adjusted models, low nSES was significantly associated with the LumB (odds ratio for quartile 1 vs quartile 4 [ORQ1vQ4 ], 1.31; 95% confidence interval [CI], 1.11-1.54; P for trend = .005) and TNBC subtypes (ORQ1vQ4 , 1.32; 95% CI, 1.02-1.71; P for trend = .037) relative to LumA. Conversely, individual education was significantly associated with only the Her2-e subtype (odds ratio for high school degree or less vs postgraduate, 1.68; 95% CI, 1.03-2.75; P for trend = .030) relative to LumA. Individual income was not significantly associated with any BC subtype. nSES and individual-level SES are independently associated with different BC subtypes; specifically, low nSES and individual-level education are independent predictors of more aggressive BC subtypes relative to LumA.


Ultrasonographic and Clinical Characteristics of Schwannoma of the Hand.
The purpose of this study was to report the ultrasonographic findings and clinical features of schwannoma of the hand. We enrolled 8 patients who were initially diagnosed with ganglion by ultrasonography but finally with schwannoma by a tissue biopsy. We retrospectively analyzed the ultrasonographic findings of eight patients including echogenicity, internal homogeneity, posterior enhancement, internal vascularity, and clinical manifestations such as the occurrence site, tenderness, Tinel's sign, and paresthesia before the surgery. The occurrence sites were as follows: two cases on the thenar area, one case on the second web space, three cases on the third web space, one case on the radiovolar aspect of the proximal phalanx of the index finger, and one case on the radiovolar aspect of the proximal phalanx of the middle finger. Four patients suffered from tenderness and pain on presentation, and all patients had pain around the mass before presentation. Tinel's sign was present without paresthesia in one case. Ultrasonography revealed cystic lesions showing clear margins in all cases, and two of them had acoustic enhancement without internal flow. It may not be easy to diagnosis schwannoma of the hand with ultrasonography alone when the lesion is small because of the similarity to the ultrasonographic findings of ganglion. Therefore, it is necessary to consider the possibility of schwannoma if a mass near the digital nerve or cutaneous nerve branch is accompanied by dull pain and tenderness.


Contribution to the fauna of the genus Meroplius Rondani, 1874 (Diptera, Sepsidae) of the Australasian/Oceanian region.
Flies of the genus Meroplius Rondani, 1874 (Diptera: Sepsidae) of the Australasian and Oceanian regions, which includes 3 species, are reviewed. Generic and species descriptions and a key for the determination of species are given, and distribution data are summarized. One species, Meroplius timikana sp. nov. is described as new to science.


LKB1 loss cooperating with BRAF V600E promotes melanoma cell invasion and migration by up-regulation MMP-2 via PI3K/Akt/mTOR pathway.
The serine/threonine kinase LKB1, act as a tumor suppressor, has been reported in several sporadic cancers. However, how the loss of LKB1 promotes melanoma invasion and metastasis remains incompletely understood. In this study, we inactivated LKB1expression by RNA interference in BRAF mutation and wild type melanoma cells respectively. We found LKB1 inactivation cooperate with BRAF V600E lead to melanoma cells more aggressive by a series of experiments including wound scratch test, Transwell assay. While single alteration, either LKB1 loss or BRAF V600E, fails to enhance melanoma cells invasion ability. Mechanistically, LKB1 loss synergism with BRAF V600E resulted in the activation of the PI3K/Akt/mTOR signaling pathway and significant up-regulation expression of MMP-2. In addition, LKB1 expression in human melanoma tissues was negatively associated with MMP-2 expression in the presence of BRAF V600E. Thus, our findings indicate a probable explanation on LKB1 function as a tumor suppressor in melanoma and a new therapeutic strategy for melanoma by targeting on BRAF and LKB1 together.


Dentine hypersensitivity and the placebo response. A comparison of the effect of strontium acetate, potassium nitrate and fluoride toothpastes.
A considerable number of varied agents are apparently effective in the treatment of dentine hypersensitivity. In particular, the literature supports the efficacy of strontium, potassium and fluoride containing toothpastes. This study was a double-blind, randomised, parallel group comparison of three products, namely strontium- and potassium-based desensitising toothpastes both containing fluoride, and a conventional fluoride toothpaste. A total of 131 subjects entered a 4-week wash-in phase using the conventional fluoride toothpaste, of whom 120 entered a 6-week treatment phase. Sensitive teeth were evaluated at wash-in baseline, treatment baseline and after 2 and 6 weeks use of the treatment pastes. Dentine hypersensitivity was assessed with tactile and cold air stimuli together with an overall subjective assessment. Analysis of the findings was performed using non-parametric statistical methods. Of the original 120 subjects, 112 completed the trial. All 3 toothpaste groups showed reductions in sensitivity over the 6 weeks; however, no significant differences were found between the three products at any given time. Interestingly, there was no significant change in sensitivity between wash-in baseline and treatment baseline for the cold air stimulus with the fluoride-only-based paste. However, for the group using the same fluoride toothpaste, there was significant improvement between wash-in baseline and week 6, and treatment baseline and week 6 for this stimulus, suggesting a substantial placebo effect occurred. There is a need for further investigation of a wash-in period and examination of the placebo effect when evaluating dentine hypersensitivity trials.


Risk factors for glioma in adults: a case-control study in northeast China.
A case-control study of risk factors for glioma in adults was carried out in Heilongjiang province in northeast China. Between September 1989 and May 1995, 218 histologically confirmed cases of glioma requiring surgery for tumor removal (139 astrocytoma glioma and 79 other glioma) and 436 controls with non-neoplastic and non-neurological disease were recruited and personally interviewed in the wards of six major hospitals. Controls were matched by sex, age, and area of residence. Occupational, lifestyle, and medical information was obtained through a standardized questionnaire. Use of liquor was associated with cancer risk. Compared with males who never drank liquor, males with total lifetime liquor consumption of less than 1000 liters had an adjusted odds ratio (OR) of 1.60 (95% CI: 0.89-2.88) and for more than 1000 liters, 2.73 (95% CI: 1.06-7.08). Statistically significant associations were also found for diseases related to the brain (OR: 5.75; 95% CI: 1.08-30.47) and trauma to the head requiring medical attention (OR: 4.09; 95% CI: 2.51-10.31). Increased consumption of vegetables and of fruit were each associated with decreased glioma risk. Compared with lowest quartile intake, adjusted risks associated with highest quartile intake were 0.51 (95% CI: 0.29-0.89) for total vegetables and 0.28 (95% CI: 0.16-0.51) for total fruit.


Lithium chloride attenuates root resorption during orthodontic tooth movement in rats.
Root resorption is a common side effect of orthodontic treatment. In the current study, lithium chloride (LiCl), a Wnt signaling activator, was examined to determine its effect on root resorption. In total, 10 Sprague Dawley rats were randomly allocated into the experimental group (EG) and control group (CG). Each group consisted of five subjects. By using closed nickel-titanium coil springs, a 50-g force was applied between the upper incisors and the maxillary right first molars in order to mimic orthodontic biomechanics in the EG and CG for 14 days. During the 14 days, the EG rats were gavage-fed 200 mg/kg LiCl every 48 h. Next, digital radiographs were captured using a micro-computational tomography scanner. The movement of the maxillary first molars and the root resorption area ratio were measured electronically on the digital radiographs. The outcomes were analyzed using ANOVA. Following 14 days of experimental force application, all rats had spaces of varying sizes between the first and second right maxillary molars. The average distance measured in the CG was slightly higher than in the EG, however, the difference was not found to be statistically significant (P=0.224). Root resorption craters were observed in the groups following the experiment. Rough cementum areas were observed on the mesial surface of the distobuccal and distopalatal roots. The mean root resorption area ratio of CG was significantly greater than EG (P<0.05). Results of the present study indicate that LiCl can attenuate orthodontically induce root resorption during orthodontic tooth movement. The effect of LiCl on tooth movement is insignificant.


The neuronal transport mechanism for noradrenaline is not influenced by the ATP analogue ATP gamma S.
Noradrenaline is taken up in noradrenergic neurones via a desipramine-sensitive transport system (uptake1). There are reports which describe the activity of uptake1 being increased by extracellular ATP and ATP gamma S. This was attributed to a protein kinase-mediated mechanism. We reevaluated this phenomenon since a modulation of uptake1 by extracellular ATP would be of great physiological relevance. In clonal rat pheochromocytoma cells (PC12) we determined the kinetic parameters, Km and Vmax, of noradrenaline transport in the absence and presence of ATP gamma S. The addition of 0.1 mumol/L ATP gamma S had no effect on initial rates of specific noradrenaline transport. Only a slightly increased non-specific noradrenaline flux in the presence of ATP gamma S could be observed. On the basis of our results, there is no evidence for the modulation of the uptake1 carrier by ATP gamma S.


[Infections with Mycobacterium tuberculosis and MOTT (Mycobacteria other than tuberculosis) in HIV infected and AIDS patients].
AIDS is characterized by a variety of opportunistic infections and malignant tumours. Tuberculosis occurs 500 times more often in HIV-infected patients than in patients with normal immunological function. In contrast to tuberculosis, which is diagnosed before the 1st AIDS defining disease, MOTT-infections are complications of late stage HIV-disease. The occurrence of drug-resistant strains of mycobacterium tuberculosis is a problem to be solved by the public health services. In contrast in MOTT-infections therapeutic problems exist.


Efficient training of RBF networks for classification.
Radial Basis Function networks with linear outputs are often used in regression problems because they can be substantially faster to train than Multi-layer Perceptrons. For classification problems, the use of linear outputs is less appropriate as the outputs are not guaranteed to represent probabilities. We show how RBFs with logistic and softmax outputs can be trained efficiently using the Fisher scoring algorithm. This approach can be used with any model which consists of a generalised linear output function applied to a model which is linear in its parameters. We compare this approach with standard non-linear optimisation algorithms on a number of datasets.


The role of radical surgery in the management of CEAP C5/6 and lipodermatosclerosis.
Aim Analysis of the radical removing of the dermatosclerotic tissues and ulcer(s) with perforator veins dissection as well as local wound and standard compression treatment of CEAP C5/6 stage in a prospective comparative cohort study. Primary endpoint is to compare the results of the one-year follow-up regarding quality of life, vein clinical severity score, and ulcer healing process. Secondary endpoint is the precise presentation of the surgical technique. Tertiary endpoint is to demonstrate the photo-documented results of the postoperative wound treatment protocol. Method Clinical and statistical comparison of radical surgery versus solely wound care and compression in a cohort of 15 patients in each group (Groups 1, 2). In Group 1, radical removing of the dermatosclerotic pannicule and leg ulcer, perforator vein dissection, great saphenous vein, or small saphenous vein was performed. Quality of life , pain intensity, vein clinical severity score and patients' load capacity were compared. The tissue oxygen saturation changes were monitored via near infra-red spectroscopy. Results Both groups were statistically comparable. Wound healing in the operated group was 100% versus 60% in the second one, the difference was significant, p = 0.006. The quality of life: 45.33 versus 36.8, p < 0.001, intensity of leg restless and pain: 2.28 versus 5.3, p < 0.001, changes of vein clinical severity score: 5.27 versus 20.93, p < 0.001, changes of tO2sat: 19.00 versus 6.07 in the upper third of the leg p < 0.001, proved significantly better in group 1 compared to 2. Load capacity was significantly better in group 1 than 2 at the end of the study. The average wound healing time was 113 days in group 1. Conclusion The radical surgery provides significantly better results, considering quality of life, vein clinical severity score, load capacity than the conservative treatment in this study.


Influence of D-galactosamine and alpha-naphthylisothiocyanate on the activities of some intestinal enzymes.
The activities of lactase, sucrase, maltase and gamma-glutamyl transferase (gamma-GT) were determined in homogenates of rat jejunal mucosa 24 h after acute administrations of D-galactosamine (GALN) (1.855 mmol/kg; i.p. injection) and alpha-naphthyl-isocyanate (ANIT) (0.540 mmol/kg; given by gastric tube). The animals were fasted either 24 h or 72 h prior to sacrifice. In rats fasted only 24 h, GALN treatment resulted in a pronounced decrease in lactase and in a moderate elevation of sucrase and maltase. ANIT clearly reduced lactase and, to a lesser extent, sucrase, while it increased maltase. Seventy-two hour fasting has a modifying role. All disaccharidase activities tended to decrease, except for maltase in the ANIT treated group, where an increase was recorded. gamma-GT showed no significant changes after either GALN or ANIT treatment in rats fasted 24 h. However, the 72-hour food deprivation diminished it in ANIT intoxication. It is obvious that the intestinal enzymes are influenced by the hepatic damage produced by GALN and ANIT.


[Diet counseling for hypertensive patients. What measures make sense?].
The leading principles of diet and lifestyle in the treatment of hypertension are identical to those applicable to elevated LDL cholesterol. The following measures or recommendations apply: fewer saturated fatty acids, weight reduction, more exercise, more fruit and vegetables, alcohol--if at all--strictly in moderation, no smoking. Patients with hypertriglyceridemia should give greater preference to vegetables rather than fruits with their higher content of fructose. The effect on the blood pressure is greater the more of these principles are applied. As in the case of blood pressure-lowering drugs, the response of the individual patient to dietary measures also varies considerably. Nevertheless, lifestyle measures should definitely not be dismissed. Rather, the individual principles should be investigated for their efficacy.


Pathogens causing urinary tract infections in infants: a European overview by the ESCAPE study group.
Knowledge of the distribution spectrum of causative organisms and their resistance patterns has become a core requirement for the rational and effective management of urinary tract infections. In the context of a prospective trial on the use of antibiotic prophylaxis in infants with underling kidney malformations, we conducted an online survey among paediatric nephrologists on positive urine cultures (July 2010-June 2012) from both hospitalized and non-hospitalized infants under 24 months of age. We collected 4745 urine cultures (UCs) at 18 units in 10 European countries. Escherichia coli was the most frequent bacterium isolated from UCs; however, in 10/16 hospitals and in 6/15 community settings, E. coli was isolated in less than 50% of the total positive UCs. Other bacterial strains were Klebsiella, Enterococcus, Proteus and Pseudomonas not only from hospital settings. E. coli showed a high resistance to amoxicillin and trimethoprim and variable to cephalosporin. Nitrofurantoin had a good rate of efficacy, with 11/16 hospitals and 11/14 community settings reporting a resistance lower than 5%. E. coli is the most common organism causing UTIs in infants; however, other bacterial strains are frequently isolated. As a result, antibiotic prophylaxis should be more elastic and adaptable over time in order to guarantee maximum efficacy.


Inhibition of tissue factor activity reduces the density of cellular network formation in an in vitro model of angiogenesis.
Tissue factor (TF) is a transmembrane glycoprotein that was originally recognized for its ability to initiate the extrinsic pathway of coagulation. More recently, additional functions of TF in cellular signalling have emerged, notably the role of TF in vasculogenesis and angiogenesis. We have described previously the ability of a peptide derived from the apolipoprotein B100 (apoB100) moiety of low-density lipoproteins (KRAD14) to inhibit the procoagulant function of TF. In this study, we demonstrate the ability of the KRAD14 peptide to attenuate the density of cellular network structures of T24 cells grown on specialized matrix (Matrigel). In addition, an alternative inhibitor of TF activity, the TF8 5G9 antibody, also reduces the density of cellular network formation. Targeted use of a stable structural equivalent of the KRAD14 peptide may thus prove useful in the prophylactic treatment of diseases whose pathologies feature the formation of neovascular tissue, e.g. tumour growth and metastasis, rupture of atherosclerotic plaques and retinopathy secondary to diabetes.


Functional and morphologic outcomes of CAD/CAM-assisted versus conventional microvascular fibular free flap reconstruction of the mandible: A retrospective study of 25 cases.
Mandibular reconstruction using fibula free flap has been improved in the last decade with computer-aided design and computer-aided manufacturing (CAD/CAM) but any functional and aesthetic evaluation of their reattempts has been realized. Aim of this retrospective study is to compare functional and morphologic outcomes after mandibular reconstruction with fibula free flap using CAD/CAM or conventional peroperative shaping for mandible reconstruction. Moreover, we compared quality of life, patient and surgery characteristics in the two groups. We realized a monocentric retrospective analyzed of 25 cases of unilateral mandibular reconstruction divided in two groups, using CAD/CAM (12 patient) or conventional approach (13 patients) between April 2012 and March. Functional and aesthetic measurements were performed postoperatively. Mouth opening, laterotrusion and protrusion of the mandible seemed to be improved in CAD/CAM group compared with conventional group but did not differ significantly. Quality of life, bite force, masticatory ability, eating and chewing satisfaction, appearance and social activity satisfaction did not differ significantly in the two groups. Even if no superiority has been established for CAD/CAM group regarding functional and aesthetic outcomes, a prospective design of future studies and transdisciplinary approach should improve our data and their interpretations. Thus, the integration of virtual planning and guided surgery is definitely of significant value and must be considered in complex maxillofacial reconstructions.


Characterization of purine receptors in mouse thoracic aorta.
The contracting and relaxing effects of purines and UTP were investigated on rings of mouse thoracic aorta in vitro. UTP, ATP gamma S, and alpha-beta-Methyleneadenosine 5'triphosphate contracted rings with and without endothelium. On the contrary, adenosine, AMP, ADP, ATP, and 2-(methylthio)adenosine 5'-diphosphate had no effect on relaxed rings. When rings were tonically contracted by U46619 a thromboxane A2 analogue, ATP, ADP, ATP gamma S, 2-(methylthio)adenosine 5'-diphosphate, and UTP caused endothelium-dependent but not independent relaxations.I conclude that ATP acts on P2Y2 and P2Y1 receptors on the endothelial cells to cause endothelium-dependent relaxation. In this tissue, the relaxing effect of ATP dominates by endothelium-dependent ways when aorta rings are contracted by a stable thromboxane A2 analog. However receptors mediating contraction in response to purines and pyrimidines are present on smooth muscle cells. Indeed, the stimulation of P2Y receptors by UTP as well as the activation of P2X family receptors by ATP gamma S causes a contraction. The potential contractile effect of ATP seems masked by its hydrolysis by ectonucleotidases.


Comparative immunology of algal biliproteins.
The three spectroscopically distinct classes of phycobiliproteins characteristic of the Cyanophyta and Rhodophyta-phycocyanins, allophycocyanins, and phycoerythrins-share no common antigenic determinants detectable by the Ouchterlony double diffusion technique. Each class of phycobiliprotein, from both Cyanophyta and Rhodophyta, possesses a strong determinant common to all members of that class. With respect to an antiserum directed against a specific cyanophytan biliprotein, all heterologous biliproteins of the same class are immunologically identical, as shown by the fact that absorption with a given heterologous antigen simultaneously eliminates crossreactions with other heterologous antigens. A cryptophytan phycoerythrin was found to be immunologically unrelated to any of the cyanophytan or rhodophytan biliproteins examined.


Ca2+ release-activated Ca2+ channel blockade as a potential tool in antipancreatitis therapy.
Alcohol-related acute pancreatitis can be mediated by a combination of alcohol and fatty acids (fatty acid ethyl esters) and is initiated by a sustained elevation of the Ca(2+) concentration inside pancreatic acinar cells ([Ca(2+)]i), due to excessive release of Ca(2+) stored inside the cells followed by Ca(2+) entry from the interstitial fluid. The sustained [Ca(2+)]i elevation activates intracellular digestive proenzymes resulting in necrosis and inflammation. We tested the hypothesis that pharmacological blockade of store-operated or Ca(2+) release-activated Ca(2+) channels (CRAC) would prevent sustained elevation of [Ca(2+)]i and therefore protease activation and necrosis. In isolated mouse pancreatic acinar cells, CRAC channels were activated by blocking Ca(2+) ATPase pumps in the endoplasmic reticulum with thapsigargin in the absence of external Ca(2+). Ca(2+) entry then occurred upon admission of Ca(2+) to the extracellular solution. The CRAC channel blocker developed by GlaxoSmithKline, GSK-7975A, inhibited store-operated Ca(2+) entry in a concentration-dependent manner within the range of 1 to 50 μM (IC50 = 3.4 μM), but had little or no effect on the physiological Ca(2+) spiking evoked by acetylcholine or cholecystokinin. Palmitoleic acid ethyl ester (100 μM), an important mediator of alcohol-related pancreatitis, evoked a sustained elevation of [Ca(2+)]i, which was markedly reduced by CRAC blockade. Importantly, the palmitoleic acid ethyl ester-induced trypsin and protease activity as well as necrosis were almost abolished by blocking CRAC channels. There is currently no specific treatment of pancreatitis, but our data show that pharmacological CRAC blockade is highly effective against toxic [Ca(2+)]i elevation, necrosis, and trypsin/protease activity and therefore has potential to effectively treat pancreatitis.


Modulation of glycosaminoglycan addition in naturally expressed and recombinant human thrombomodulin.
The two major glycoforms of full-length human thrombomodulin (TM), one with (TM(CS+)) and one without (TM(CS-)) chondroitin sulfate (CS) were analyzed on Western blots of primary and transformed cells and in cells expressing recombinant TM. TM on the surface of Chinese hamster ovary and COS-7 cells is solely TM(CS-). Primary arterial endothelial cells (HAEC and HPAEC) express a greater fraction of TM with CS attached than venous cells (HUVEC). Human lung carcinoma cells (A549) express more TM(CS+) than primary cells and recombinant TM on human melanoma cells (CHL-1) occurs in two very high molecular weight forms of TM(CS+). We explored this variation in TM(CS+) with soluble recombinant TM in several cell lines and analyzed the ambiguous CS addition site in human TM by site-directed mutagenesis. Mutation of Ser474 to Ala blocks CS addition in Chinese hamster ovary and COS-7 cells but not CHL-1 cells which add CS to Ser472 and Ser474. Structure of the O-link domain affects partitioning into TM(CS+) since substituting with the decorin CS addition sequence, substituting all Ser and Thr except Ser474 with Ala, and deleting around the potential beta-turn all increase the ratio of TM(CS+) to TM(CS-). A combination of the decorin substitution and deletion of the remaining O-link domain yields the most TM(CS+).


Dissociative double photoionization of CO2 molecules in the 36-49 eV energy range: angular and energy distribution of ion products.
Dissociative double photoionization of CO(2), producing CO(+) and O(+) ions, has been studied in the 36-49 eV energy range using synchrotron radiation and ion-ion coincidence imaging detection. At low energy, the reaction appears to occur by an indirect mechanism through the formation of CO(+) and an autoionizing state of the oxygen atom. In this energy range the reaction leads to an isotropic distribution of products with respect to the polarization vector of the light. When the photon energy increases, the distribution of products becomes anisotropic, with the two ions preferentially emitted along the direction of the light polarization vector. This implies that the molecule photoionizes when oriented parallel to that direction and also that the CO(2)(2+) dication just formed dissociates in a time shorter than its typical rotational period. At low photon energy, the CO(+) and O(+) product ions separate predominantly with a total kinetic energy between 3 and 4 eV. This mechanism becomes gradually less important when the photon energy increases and, at 49 eV, a process where the two products separate with a kinetic energy between 5 and 6 eV is dominant.


Glycosyltransferase activities in Golgi complex and endoplasmic reticulum fractions isolated from African trypanosomes.
Highly enriched Golgi complex and endoplasmic reticulum fractions were isolated from total microsomes obtained from Trypanosoma brucei, Trypanosoma congolense, and Trypanosoma vivax, and tested for glycosyltransferase activity. Purity of the fractions was assessed by electron microscopy as well as by biochemical analysis. The relative distribution of all the glycosyltransferases was remarkably similar for the three species of African trypanosomes studied. The Golgi complex fraction contained most of the galactosyltransferase activity followed by the smooth and rough endoplasmic reticulum fractions. The dolichol-dependent mannosyltransferase activities were highest for the rough endoplasmic reticulum, lower for the smooth endoplasmic reticulum, and lowest for the Golgi complex. Although the dolichol-independent form of N-acetylglucosaminyltransferase was essentially similar in all the fractions, the dolichol-dependent form of this enzyme was much higher in the endoplasmic reticulum fractions than in the Golgi complex fraction. Inhibition of this latter activity in the smooth endoplasmic reticulum fraction by tunicamycin A1 suggests that core glycosylation of the variable surface glycoprotein may occur in this organelle and not in the rough endoplasmic reticulum as previously assumed.


The effects of a self-observation-based meditation intervention on acceptance or rejection of the other.
Research has demonstrated the many benefits of mindfulness training programmes for individual health and well-being. This study, however, explored whether mindfulness training might have effects on intergroup interaction. We tested the effects of a self-observation-based mindfulness course on several dimensions of acceptance of the other (i.e., non-judgement, non-reaction and observation). An initial study test a mindfulness course training (N = 197). A second study then tested its effect on intergroup relationships (N = 120). A control group was used in both studies, and the subjects were tested before and after the course. Results indicate that participation in the course favoured intergroup acceptance of the other and suggest that mindfulness training represents a useful educational method for reducing social discrimination.


Subclavian cannulation. Valuable dialysis access alternative.
The subclavian vein was used for temporary dialysis access in 67 patients. There were 733 dialysis treatments performed using a total of 87 catheters during the study period. The catheters were left in place for an average of 24.5 days per patient and 18.9 days per catheter. A mean of 10.9 dialysis treatments per patient, and 8.4 dialysis treatments per catheter were performed. Seven patients expired with their catheters indwelling. None of these deaths were related to the catheter. There were 21 associated catheter complications. Twelve of these catheter complications were corrected by changing the catheter over a guide wire. The technique for catheter insertion, proper catheter care including home care, and complications due to the catheters are discussed. Subclavian catheter dialysis access appears to be a valuable adjunct for dialysis and has replaced the use of Scribner shunts and repeated femoral catheterizations for temporary access in our institution.


The functional outcomes of coloanal and low colorectal anastomoses with reservoirs after low rectal cancer resections.
Nearly half of patients undergoing low anterior rectal cancer resection have a functional sequelae after straight coloanal or low colorectal anastomoses (SA), including low anterior rectal resection syndrome, which combines stool fragmentation, urge incontinence, and incontinence. SA are responsible for anastomotic leakage rates of 0 to 29.2 per cent. Adding a colonic reservoir improves the functional results while reducing anastomotic complications. These colonic reservoir techniques include the colonic J pouch (CJP), transverse coloplasty (TC), and side-to-end anastomosis (STEA) procedures. The aim of this literature review was to compare the functional outcomes of these three techniques from a high level of evidence. CJP with a 4- to 6-cm reservoir is a good surgical option because it reduces functional impairments during the first year, and probably up to 5 years, but is not always feasible. TC appears to perform as well as CJP, is achievable in over 95 per cent of patients, but still with some doubts about a higher anastomotic leakage rate and worse functional outcomes. STEA appears equivalent to CJP in terms of morbidity and even better functional outcomes. STEA, with a terminal side segment size of 3 cm, is feasible in the majority of nonobese patients, combines good functional results, has low anastomotic leakage rates, and is easy to complete.


Toxin-antitoxin operon kacAT of Klebsiella pneumoniae is regulated by conditional cooperativity via a W-shaped KacA-KacT complex.
Bacterial toxin-antitoxin pairs play important roles in bacterial multidrug tolerance. Gcn5-related N-acetyltransferase (GNAT) toxins inhibit translation by acetylation of aminoacyl-tRNAs and are counteracted by direct contacts with cognate ribbon-helix-helix (RHH) antitoxins. Our previous analysis showed that the GNAT toxin KacT and RHH antitoxin KacA of Klebsiella pneumoniae form a heterohexamer in solution and that the complex interacts with the cognate promoter DNA, resulting in negative autoregulation of kacAT transcription. Here, we present the crystal structure of DNA-bound KacAT complex at 2.2 Å resolution. The crystal structure revealed the formation of a unique heterohexamer, KacT-KacA2-KacA2-KacT. The direct interaction of KacA and KacT involves a unique W-shaped structure with the two KacT molecules at opposite ends. Inhibition of KacT is achieved by the binding of four KacA proteins that preclude the formation of an active KacT dimer. The kacAT operon is auto-regulated and we present an experimentally supported molecular model proposing that the KacT:KacA ratio controls kacAT transcription by conditional cooperativity. These results yield a profound understanding of how transcription GNAT-RHH pairs are regulated.


Role of mineral nutrition in minimizing cadmium accumulation by plants.
Cadmium (Cd) is a highly toxic heavy metal for both plants and animals. The presence of Cd in agricultural soils is of great concern regarding its entry into the food chain. Cadmium enters into the soil-plant environment mainly through anthropogenic activities. Compounds of Cd are more soluble than other heavy metals, so it is more available and readily taken up by plants and accumulates in different edible plant parts through which it enters the food chain. A number of approaches are being used to minimize the entry of Cd into the food chain. Proper plant nutrition is one of the good strategies to alleviate the damaging effects of Cd on plants and to avoid its entry into the food chain. Plant nutrients play a very important role in developing plant tolerance to Cd toxicity and thus, low Cd accumulation in different plant parts. In this report, the role of some macronutrients (nitrogen, phosphorus, sulfur and calcium), micronutrients (zinc, iron and manganese), and silicon (a beneficial nutrient) has been discussed in detail as to how these nutrients play their role in decreasing Cd uptake and accumulation in crop plants.


Taxonomy of lactic acid bacteria from spoiled, vacuum packaged vienna sausages by total soluble protein profiles.
To resolve the taxonomic status of sixty-one lactic acid bacteria isolated from spoiled, vacuum packaged vienna sausages, a computer assisted analysis of total soluble protein profiles was undertaken. Sixty-two% of the strains in the study were recovered in fourteen clusters at the 72% similarity level, indicating high degree of heterogeneity among the strains examined. Two clusters representing Leuconostoc species were the largest and most homogeneous, containing twenty strains between them. One cluster contained both typical Lactobacillus saké and Lactobacillus curvatus strains, indicating the inability of protein profiles to consistently differentiate between all strains of these two species. The presence of an independent Lactobacillus curvatus grouping and the clustering of some atypical strains with Lactobacillus saké isolates, however, indicated that the atypical strains may be closely related to Lactobacillus saké.


Beta-blocker treatment of dilated cardiomyopathy. Beneficial effect of carteolol in mice.
The effects of carteolol, a nonselective beta-adrenergic receptor blocker with intrinsic sympathomimetic activity, were compared with those of metoprolol in a murine model of viral myocarditis and dilated cardiomyopathy caused by encephalomyocarditis virus. In the acute experiment, BALB/c and DBA/2 mice were inoculated with encephalomyocarditis virus. BALB/c mice were then given carteolol at 1 (n = 10), 10 (n = 10), 30 (n = 11), or 100 mg/kg (n = 9) daily, and DBA/2 mice were given carteolol at 1 (n = 9) or 10 mg/kg (n = 9) daily starting the day of inoculation. Controls were given distilled water (n = 23 for BALB/c mice and n = 8 for DBA/2 mice). BALB/c mice were killed on day 7, and DBA/2 mice were killed on day 14. In the subacute experiment, DBA/2 mice were inoculated with the virus and then given carteolol at 1 (n = 12) or 10 mg/kg (n = 16), or distilled water (n = 27) daily, starting on day 14. Mice were killed on day 28. Virus replication, murine survival, heart weight to body weight ratio, and histopathological findings were similar in each group in the acute and subacute experiments. In the chronic experiment, DBA/2 mice were inoculated with the virus and were then given carteolol at 1 (n = 13) or 10 mg/kg (n = 9), metoprolol at 30 mg/kg (n = 9), or distilled water (n = 31) daily, starting on day 14. Mice were killed on day 104. Heart weight to body weight ratio and histopathological scores were significantly lower in mice given carteolol than in the infected control group. Furthermore, left ventricular cavity dimension, left ventricular wall thickness, and myocardial fiber diameter of the left ventricle were significantly reduced in mice given carteolol compared with the control group. Metoprolol did not cause any significant changes compared with the control group. This study suggests that carteolol prevents the development of myocardial lesions similar to those in dilated cardiomyopathy after myocarditis in the chronic stage.


High-risk sexual behaviours in young people experiencing a first episode of psychosis.
The sexual health of adults with schizophrenia is poorer than the general population; however, less is known about young people experiencing a first episode of psychosis (FEP). The aim of this study was to explore the high-risk sexual behaviours and sexual well-being indicators of a cohort of young people with FEP. Data collected from young people (15-24 years) with FEP attending the EPPIC service in Melbourne and participating in a physical health intervention were analysed. Baseline trial data collected on sexual health and high-risk behaviours, psychiatric symptomology, functioning, and substance use are presented by gender. Associations between symptomology and functioning with sexual behaviour are explored. A total of 69 young people were included in this study; mean age was 19.6 years (SD±2.8), 53.6% were male, 59.6% identified as heterosexual, and 21.7% were currently in a relationship. Within the cohort, 78.3% had ever been sexually active. Of these, 44.2% consistently used a condom at last sex act and 35.7% used barrier contraception consistently, 22.5% had previously been pregnant, and 18.6% had tested positive for an STI. Finally, young people were more likely to have been sexually active if they were currently using substances. These findings suggest that high rates of high-risk sexual behaviour remain an issue for young people experiencing a first episode of psychosis. Promoting sexual well-being and communication skills between sexual partners should be targeted to ensure that high-risk sexual health outcomes are mitigated as early as possible.


Iron acquisition through the bacterial transferrin receptor.
Transferrin is one of the sources of iron that is most readily available to colonizing and invading pathogens. In this review, we look at iron uptake by the bacterial transferrin receptor that is found in the families Neisseriaceae, Pasteurellaceae and Moraxellaceae. This bipartite receptor consists of the TonB-dependent transporter, TbpA, and the surface lipoprotein, TbpB. In the past three decades, major advancements have been made in our understanding of the mechanism through which the Tbps take up iron. We summarize these findings and discuss how they relate to the diversity and specificity of the transferrin receptor. We also outline several of the remaining unanswered questions about iron uptake via the bacterial transferrin receptor and suggest directions for future research.


Prediction and Prevention of Preterm Birth: A Prospective, Randomized Intervention Trial.
The study aimed to determine if a program of mid-trimester serum proteomics screening of women at low risk for spontaneous preterm birth (sPTB) and the use of a PTB risk-reduction protocol in those whose results indicated an increased risk of sPTB would reduce the likelihood of sPTB and its sequelae. Prospective comparison of birth outcomes in singleton pregnancies with mid-trimester cervical length ≥2.5 cm and at otherwise low risk for sPTB randomized to undergo or not undergo mid-trimester serum proteomics screening for increased risk of sPTB (NCT03530332). Screen-positive women were offered a group of interventions aimed at reducing the risk of spontaneous PTB. The primary outcome was the rate of sPTB <37 weeks, and secondary outcomes were gestational age at delivery, total length of neonatal stay, and NICU length of stay (LOS). Unscreened and screen-negative women received standard care. The adaptive study design targeted a sample size of 3,000 to 10,000 women to detect a reduction in sPTB from 6.4 to 4.7%. Due to limited resources, the trial was stopped early prior to data unblinding. A total of 1,191 women were randomized. Screened and unscreened women were demographically similar. sPTB <37 weeks occurred in 2.7% of screened women and 3.5% of controls (p = 0.41). In the screened compared with the unscreened group, there were no between-group differences in the gestational age at delivery, total length of neonatal stay, and NICU LOS. However, the NICU LOS among infants admitted for sPTB was significantly shorter (median = 6.8 days, interquartile range [IQR]: 1.8-8.0 vs. 45.5 days, IQR: 34.6-79.0; p = 0.005). Mid-trimester serum proteomics screening of women at low risk for sPTB and the use of a sPTB risk-reduction protocol in screen-positive patients did not significantly reduce the rate of sPTB compared with women not screened, though the trial was underpowered thus limiting the interpretation of negative findings. Infants in the screened group had a significantly shorter NICU LOS, a difference likely due to a reduced number of infants in the screened group that delivered <35 weeks. · Mid-trimester serum proteomics screening of women at low risk for sPTB and the use of a sPTB risk-reduction protocol in screen-positive patients did not significantly reduce the rate of sPTB, though the trial was underpowered.. · NICU LOS following sPTB was significantly shortened among women who underwent screening and risk-reduction management.. · The use of serum biomarkers may contribute to a practical strategy to reduce sPTB sequelae..


Alternative therapy in glaucoma management: is there any role?
Glaucoma is one of the leading causes of blindness worldwide. Various randomized controlled clinical trials have shown that lowering intraocular pressure (IOP) does reduce progression of primary open-angle glaucoma. However, there is lots of interest in nonpharmacological options that includes lifestyle adjustment and alternative and complementary therapy (ACT). At least 5% glaucoma population uses ACT. Various lifestyle activities like exercise and alcohol can reduce IOP by 1 to 2 mm Hg but would have small effect on glaucoma. The psychological stress can increase IOP. Hypothetically and few studies do show neuroprotective effect (or effect on ocular blood flow) of alcohol, Gingko biloba, bilberry, but the current evidence is weak for its routine use. We must also remember the side effects of 'medications' (e.g., marijuana, alcohol) before promoting as remedy for glaucoma. In current armamentarium of glaucoma management, ACT cannot substitute the conventional treatment available to lower IOP.


Developmental stage-dependent expression of an alpha2,8-trisialic acid unit on glycoproteins in mouse brain.
The monoclonal antibody mAb.A2B5 is a marker for the detection of oligodendrocyte progenitor cells that differentiate into type-2 astrocytes and oligodendrocytes. It is also a useful antibody for separating these cells from other lineage populations. The epitope of this antibody is considered to be the gangliosides GT3 and GQ1c. In this study, we sought to define more precisely the structure of the epitope. Accordingly, we chemically synthesized defined oligosialic acid structures linked to phosphatidylethanolamine and bovine serum albumin and used these to determine the antigenic specificity. mAb.A2B5 recognized the Neu5Acalpha2-->8Neu5Acalpha2-->8Neu5Acalpha--> structure on both glycolipids and glycoproteins. We then examined whether the mAb.A2B5 epitope exists on glycoproteins in developing mouse brains. Western blot analyses revealed the expression of four glycoproteins reactive with the mAb.A2B5, and their expression was dependent on the stage of neural development. All the immunoreactivity in these glycoproteins with mAb.A2B5 disappeared after sialidase treatment and were resistant to chloroform/methanol extraction. These epitopes were also detected in brain homogenates from both GD3 synthetase-null and GD3/GD2 synthetase double null mice. These findings show that the alpha2,8-trisialic acid (triSia) unit recognized by mAb.A2B5 resides not only on gangliosides but also on glycoproteins in developing mouse brain. We postulate that the triSia structure on glycoproteins may be involved in oligodendrocyte differentiation, similar to the case with the alpha2,8-triSia structure on gangliosides. Real time polymerase chain reaction analysis of the developmental expression of all known ST8Sia genes, which are responsible for the biosynthesis of alpha2,8-linked Sia residues, showed that ST8Sia III gene expression correlated with expression of the triSia epitope. We suggest that ST8Sia III is the principal sialyltransferase responsible for synthesis of the alpha2,8-triSia units on glycoproteins.


Rectal wall contractility in response to an evoked urge to defecate in patients with obstructed defecation.
The aim of this study was to examine rectal sensory perception and rectal wall contractility in response to an evoked urge to defecate and to identify differences between control subjects and patients with obstructed defecation. Twenty control patients (10 men; median age, 47 (range, 17-78) years) and 29 female patients with disabling obstructed defecation (median age, 48 (range, 18-70) years) entered the study. Under radiologic control, an infinitely compliant barostat balloon was inserted over a guide wire into the proximal part of the rectum. Additionally, a latex balloon was introduced into the distal part of the rectum. This latex balloon was inflated until an urge to defecate was experienced. Simultaneously, rectal wall contractility was assessed by measuring the variations in barostat balloon volume. These variations were expressed as percentage changes from baseline volume. By comparing controls and patients with obstructed defecation, a significant difference was found regarding mean distending volume required to elicit an urge to defecate (135 +/- 38 vs. 214 +/- 87 ml of air; P < 0.001, Mann-Whitney U-test). In all controls, the evocation of an urge to defecate induced a pronounced increase in rectal tone, proximal to the distal stimulating balloon. By comparing controls and patients, the increase in rectal tone was found to be significantly higher in control subjects (35 +/- 10 vs. 9 +/- 10 percent; P < 0.001). Twenty-five patients (86 percent) showed no or only minimum (<20 percent) increase in rectal tone during the perception of an urge to defecate. In 14 of these patients, the threshold for this perception was increased. Only four patients (14 percent) showed a relatively normal increase (>20 percent) in rectal tone. However, their threshold for perception was greatly increased. The assembly used in this study provides a useful tool for investigation of rectal evacuation. In all of our patients, obstructed defecation was associated with abnormal rectal sensory perception and/or altered rectal wall contractility.


Anti-Staphylococcal Calopins from Fruiting Bodies of Caloboletus radicans.
Three new and seven known calopins were isolated from Caloboletus radicans. The structures of the new cyclocalopins, 8-deacetylcyclocalopin B (1), cyclocalopin A-15-ol (2), and 12,15-dimethoxycyclocalopin A (3), were mainly elucidated by NMR and MS data analysis. The stereochemistry of 1-3 was assigned based on NOE correlations and coupling constants and by comparison of their CD spectra with those of similar known calopins. While 1-10 were inactive against two cancer cell lines, they displayed anti-staphylococcal activity against methicillin-resistant Staphylococcus aureus strains (MRSA) with MIC values of 16-256 μg/mL. Moreover, some calopins were active against the fish pathogen Enterococcus faecalis F1B1.


The evaluation of disability and its related factors among the elderly population in Kashan, Iran.
Recent literature indicates that developing countries in Asia are aging faster than other countries in the world and disability has become one of the greater public health concern in these countries. Pausity of published data on the elderly disability in Iran signifies the importance of this study designed to evaluate the disability and its related factors among the elderly population in Kashan, Iran during 2006-2007. A cross-sectional study is conducting on a multi-stage random sample of elderly people in Kashan ages 65 years and older. Volunteer participants were included by age 65 and older and excluded if they had the medical diagnosis of Alzheimer disease. The WHO DAS II was used as the generic disability measure in this survey. The original version of WHO DAS II was translated into Farsi according to the standardized guidelines for cross-cultural adaptation of health-related measures. Upon completion of data collection the descriptive statistics will compute all the variables. Chi-square, t-test analysis and ANOVA will be used to examine significant differences between the subgroups. This is the first research protocol to study disability among the Iranian elderly population. Presently, 80% of eligible subjects have been selected. The results of this study will help to develop more effective protocols to assist Iranian elderly population with disabilities.


Cytological and Molecular Characterization of ZmWAK-Mediated Head-Smut Resistance in Maize.
Head smut, caused by the fungal pathogen Sporisorium reilianum, poses a threat to maize production worldwide. ZmWAK, a cell wall-associated receptor kinase, confers quantitative resistance to head smut disease. Here, two near-isogenic lines (NILs), susceptible line Huangzao4 and its ZmWAK-converted resistant line Huangzao4R, were used to decipher the role of ZmWAK in head smut resistance. Cytological and molecular characterization in response to S. reilianum infection was compared between two NILs. Upon S. reilianum infection, the growth of pathogen hyphae was severely arrested in the ZmWAK-converted resistant line Huangzao4R, relative to its susceptible parental line Huangzao4. Infected cells exhibited apoptosis-like features in Huangzao4R and hyphae were sequestered within dead cells, whereas pathogen invasion caused autophagy in Huangzao4, which failed to prevent hyphal spreading. Integrated transcriptomic and metabolomic analysis indicated that ZmWAK functions as a hub in the trade-off between growth and defense, whereby ZmWAK promotes cell growth in the absence of the pathogen and switches to a defense response upon S. reilianum attack. These findings shed light on an elegant regulatory mechanism governed by ZmWAK in the trade-off between growth and head smut defense.


The value of somatostatin-receptor scintigraphy in newly diagnosed endocrine gastroenteropancreatic tumors.
Conventional imaging techniques do not routinely detect endocrine gastroenteropancreatic tumors preoperatively. The purpose of this study was to determine whether the new technique of somatostatin-receptor scintigraphy would improve the detection rate of these tumors before initial treatment. In a prospective study, 55 patients with a recent diagnosis of endocrine gastroenteropancreatic tumors (22 intestinal carcinoids, 17 gastrinomas, 10 nonfunctioning pancreatic tumors, and 6 insulinomas), were examined with somatostatin-receptor scintigraphy, computed tomography, and ultrasonography. Results of the three imaging modalities were compared with findings at surgical exploration. None of the insulinomas were localized by somatostatin-receptor scintigraphy, but 4 of 6 insulinomas were detected by computed tomography and ultrasonography. Of 17 gastrinomas, 9 were detected by somatostatin-receptor scintigraphy; computed tomography and ultrasonography localized only 7. Metastases from the gastrinoma were localized by somatostatin-receptor scintigraphy in all cases; computed tomography and ultrasonography detected metastases in only 6 of 9 patients. Nonfunctioning tumors could be localized by somatostatin-receptor scintigraphy, computed tomography, and ultrasonography in 4, 7, and 8 of 10 cases, respectively. Detection rate for corresponding metastases was the same for all three imaging techniques. Primary carcinoids were identified by somatostatin-receptor scintigraphy, ultrasonography, and computed tomography in 7, 8, and 11 of 22 cases, respectively. Extra-abdominal metastases were detected by somatostatin-receptor scintigraphy in only 7 of 19 patients. In patients with insulinomas, somatostatin-receptor scintigraphy is not indicated because none of the six tumors was imaged. This holds true for nonfunctional pancreatic endocrine tumors and their metastases because no advantage for somatostatin-receptor scintigraphy was found over computed tomography and ultrasonography. In contrast, somatostatin-receptor scintigraphy is superior to computed tomography and ultrasonography for determining the extent of the disease in patients with gastrinomas or carcinoids. The problem of detecting primary tumors in these patients is not solved by somatostatin-receptor scintigraphy.


Break-up of oil-in-water emulsions by electrochemical techniques.
Electrochemically-assisted technologies can be successfully applied to the treatment of oil-in-water (O/W) emulsions. In this work, it is studied the influence of the main parameters (electrical charge passed, pH, electrolyte, oil content and operation mode) in the efficiency of these processes, when aluminium electrodes are used. The pH was found to be the most significant parameter, and good removal efficiencies were only obtained for pHs in the range 5-9. The electrical charge passed was observed to be directly related to the aluminium supplied to the waste. For a given oil concentration it is required that a minimum electrical charge is passed to break-up the emulsion. Further increases in the electrical charge lead to increase in the COD removal. The influence of the oil concentration is related to that of the electrical charge passed: for a given dose of aluminium, the higher the oil content the lower the COD-removal efficiency. Likewise, to produce the break-up of the emulsion it is required a minimum dose of aluminium (electrical charge passed), lower doses do not attain the rupture of the emulsion. The type of electrolyte and its concentration were also found to influence the process efficiency. Better efficiencies were obtained in the treatment of chloride-containing wastes and for low concentration of electrolyte. The destabilization of the O/W emulsion was found to be favoured in the discontinuous operation mode. Bridging flocculation is a primary destabilization mechanism that can explain the experimental results obtained in this work.


Screening for Chlamydia trachomatis at a university health service.
Chlamydia trachomatis is the most common sexually transmitted infection in the United States. The aim of this study was to determine the prevalence of Chlamydia in college family planning patients and to identify diagnostic indicators associated with Chlamydia. A thorough history and physical examination was performed, including culture for gonorrhea, cancer (papanicolaou test), and Chlamydia trachomatis. Chlamydia occurred in 12.6% of 419 subjects. The lack of signs and symptoms and the possibility of inaccurate historical data limit the clinical predictability of chlamydial infections. Routine screening of college women is recommended.


MicroRNA-146a inhibition promotes total neurite outgrowth and suppresses cell apoptosis, inflammation, and STAT1/MYC pathway in PC12 and cortical neuron cellular Alzheimer's disease models.
This study aimed to explore the effect of microRNA (miR)-146a inhibition on regulating cell apoptosis, total neurite outgrowth, inflammation, and STAT1/MYC pathway in Alzheimer's disease (AD). PC12 and cortical neuron cellular AD models were constructed by Aβ1-42 insult. For the former model, nerve growth factor (NGF) stimulation was previously conducted. miR-146a inhibitor and negative-control (NC) inhibitor were transfected into the two cellular AD models, and then cells were named miR-inhibitor group and NC-inhibitor group, respectively. After transfection, cell apoptosis, total neurite outgrowth, supernatant inflammation cytokines, and STAT1/MYC pathway were detected. miR-146a expression was similar between PC12 cellular AD model and control cells (NGF-stimulated PC12 cells), while miR-146a expression was increased in cortical neuron cellular AD model compared with control cells (rat embryo primary cortical neurons). In both PC12 and cortical neuron cellular AD models, miR-146a expression was reduced in miR-inhibitor group compared with NC-inhibitor group after transfection. Furthermore, cell apoptosis was attenuated, while total neurite outgrowth was elevated in miR-inhibitor group compared with NC-inhibitor group. As for supernatant inflammatory cytokines, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-17 levels were lower in miR-inhibitor group than in NC-inhibitor group. Additionally, STAT1 and c-Myc mRNA and protein expressions were attenuated in miR-inhibitor group compared with NC-inhibitor group. In conclusion, miR-146a potentially represented a viable therapeutic target for AD.


[Biochemical aspects of lymphocyte metabolism. Immunomodulating role of cyclic nucleotides].
In the present review lymphocyte metabolism has been examined with particular reference to ion and molecule flux variations through cell membrane. Furthermore, mitogenic stimulations causes a tremendous increase of cellular metabolism with remarkable modifications of oxidative processes and synthesis rate of enzymes and structural proteins. Finally, the role of cyclic nucleotides in the regulation of some lymphocyte functions has been analyzed.


Thigh muscle fat fraction is independently associated with impaired glucose metabolism in individuals with obesity.
The aim of this study was to address the intramuscular adipose tissue (IMAT) accumulation in the lower extremities and further detect the relationship between adipose tissue (AT) distribution in the muscle and glucose metabolism in subjects with obesity. We conducted a cross-sectional study in 120 Chinese obese adults (80 male and 40 female) with BMI ≥ 28 kg/m2. MRI was applied to access the IMAT content in lower extremities. The oral glucose tolerance test was used to evaluate the glucose metabolism and insulin secretion in all individuals. The correlations between glucose metabolism and the fat content of the lower extremities were further assessed. Among 120 included subjects, 54 were classified as subjects with normal glucose tolerance (NGT) and 66 with impaired glucose regulation (IGR). We presented that those with IGR had higher fat accumulation in semitendinosus, adductor magnus, gracilis and sartorius than those with NGT (all P < 0.05). In sex-specific analyses, females have higher IMAT in adductor magnus than males (P < 0.001). Males with IGR had higher fat fraction of semitendinosus and sartorius than those with NGT (P = 0.020, P = 0.014, respectively). Logistic regression analyses revealed that IMAT content in semitendinosus was the independent factor of IGR in individuals with obesity after adjustment for age, gender, triglycerides, creatinine and albumin (odds ratio: 1.13, 95% CI: 1.02-1.26, P = 0.024). Increased adipose tissue accumulation in thigh muscles was associated with glucose dysregulation in patients with obesity. IMAT content in semitendinosus may serve as a possible risk factor for impaired glucose metabolism.


Gastric pull-up vs deltopectoral flap for reconstruction of the cervical esophagus.
Reconstruction of the cervical esophagus and pharynx after a total laryngopharyngectomy for patients with advanced hypopharyngeal cancer still remains a problem for surgeons. The results of two procedures, the tubed deltopectoral flap reconstruction and the gastric pull-up operation with pharyngogastric anastomosis, which are used in fulfilling postoperative deglutition requirements, were compared. There were nine patients in the gastric pull-up group and eight patients in the deltopectoral flap group. The groups were reasonably comparable with regard to age, sex, preoperative radiotherapy, and stage of tumor. Three of the patients in the gastric pull-up group were operated on for palliation alone. Average operation-to-swallow time was 12 days for the gastric pull-up groups and 90 days for the deltopectoral flap group. Reconstruction of the gullet with the stomach pull-up operations seems to be superior to the tubed deltopectoral flap. This is especially true if the operation is palliative because the patient is unlikely to survive more than one year after surgery.


Drug-Drug-Induced Akathisia: Two Case Reports.
Extrapyramidal side effects of psychotropic medicines are usually experienced by patients in the first few weeks of initiating therapy. Patients stabilized on these medications who present with distressing complaints akin to akathisia may be triggered by other factors. This report presents two cases of drug-drug-induced akathisia. Case A is a patient with schizophrenia who was being managed with risperidone 2 mg tablet daily for the past 3 years. She fell ill and reported to a nearby clinic where she was prescribed ciprofloxacin and artemether/lumefantrine tablets for the treatment of an infection and malaria. She presented 7 days later to her psychiatrist with complaints of restlessness, tremor, palpitations, insomnia, and resurgence of obsessive thoughts. Case B is a patient who was diagnosed with first-episode psychotic depression and admitted for 10 days. Her medications on admission were fluphenazine decanoate 25 mg depot injection once, olanzapine 10 mg tablet daily, and fluoxetine 20 mg capsule daily. On discharge, ciprofloxacin 500 mg tablet every 12 hours for 5 days and fluconazole 150 mg capsule once were added to her medications for the treatment of a urinary tract infection. She reported back to the hospital a day after discharge with complaints of restlessness, "seizures," tremor, abdominal discomfort, and weight gain. Both patients were diagnosed with akathisia using ICD-10 classification and the Barnes akathisia rating scale and managed with anticholinergics, benzodiazepines, and beta blockers. Other measures employed in managing the akathisia included reducing the dose of the antipsychotic and/or switching antipsychotics. Despite these management measures, the symptoms of akathisia persisted and only resolved after 4weeks. Upon the resolution of symptoms, Case A continued treatment on olanzapine 5 mg tablet daily and fluoxetine 20 mg capsule daily while Case B continued treatment on risperidone 2 mg tablet daily and fluoxetine 20 mg capsule daily. Using Naranjo's adverse drug reaction causality assessment scale, Medscape drug interaction checker, and literature review, a possible and probable case of drug-drug-induced akathisia was made for Case A and Case B. This report is to create more awareness about psychotropic-antimicrobial-induced akathisia. The information underpins the need for health professionals to consider adverse drug-drug interactions as the probable cause of extrapyramidal side effects experienced by patients on antipsychotics.


[Generation of transgenic mice expressing human lysozyme in mammary gland].
To evaluate the feasibility of generating animal mammary gland bioreactors expressing human lysozyme (hLYZ). The recombinant vector p205C3-hLYZ, as a result of connecting the hLYZ cDNA with the mammry gland expression vector p205C3, was used to generate transfer genic mice by microinjection. A total of 136 F0 mice were obtained, of which 7 (2 females and 5 males) and 4 (1 females and 3 males) were found to contain the transfer-gene by PCR and Southern blotting respectively. The results of Western blotting indicated that the expressed protein had the same molecular weight as that of normal hLYZ. From the F1 generation on, the mice mated only with their brothers or sisters and a colony of F7 transgenic mice was obtained. Among the offspring, the female transgenic mice maintained and expressed the transfer-gene stably with an expression level as high as 750 mg/L. The expressed protein had strong tissue specificity, and in addition to the mammary glands, some degree of ectropic expression in the spleens and intestines of the transgenic mice was confirmed by dot blotting assay. These data indicate that the mice mammary gland bioreactors expressing hLYZ have been successfully generated.


Clinical assessment of freezing of gait in Parkinson's disease from computer-generated animation.
The current 'gold standard' for clinical evaluation of freezing of gait (FOG) in Parkinson's disease (PD) is determination of the number of FOG episodes from video by independent raters. We have previously described a robust technique for objective FOG assessment from lower-limb acceleration. However, there is no existing method for validation of autonomous FOG measures in the absence of video documentation. In this study we compared the results of clinical evaluation of FOG from computer-generated animations (derived from body-mounted inertial sensors) during a timed up and go test with the 'gold standard' of clinical video assessment, utilizing a cohort of 10 experienced raters from four PD centers. Agreement between the 10 clinical observers for scoring of FOG from computer animations was more robust for the relative duration of freeze events (percent time frozen; intraclass correlation coefficient of 0.65) than number of FOG episodes, and was comparable with clinical evaluation of the patient from video (intraclass correlation coefficient 0.73). This result suggests that percent time frozen should be considered (along with number of FOG events) to better convey FOG severity. The ability of clinical observers to quantify FOG from computer-generated animation derived from lower-limb motion data provides a potential approach to validation of accelerometry-based FOG identification outside of the clinic.


Rescue left main coronary artery stenting for acute myocardial ischemia after coronary angiography in a 7-year-old girl with homozygous familial hypercholesterolemia.
Homozygous familial hypercholesterolemia (HFH), resulting from mutation of the low-density lipoprotein (LDL) receptor gene with subsequent defective catabolism of the LDL cholesterol, leads to premature atherosclerosis and coronary artery disease. We report a successful urgent stent implantation in a 7-year-old patient with HFH and a severe left main coronary artery stenosis, who presented critical acute myocardial ischemia immediately after left coronary angiography. Percutaneous transluminal coronary angiography with stent implantation allowed for rapid coronary flow reestablishment without sequelae. Aggressive lipid-lowering therapy with high doses statins and LDL-apheresis was maintained, together with lifelong antiaggregant acetylsalicylic treatment with good short-term patency of the stent at 1-year follow-up. In conclusion, coronary artery stent implantation may be considered as a valid rescue therapeutic alternative for pediatric patients with HFH and severe ostial coronary stenosis in case of emergency.


Positive and negative electrorheological response of alginate salts dispersed suspensions under electric field.
Electrorheological (ER) effects of alginic acid and alginate salts (Na(+) alginate, NH(4)(+) alginate, and Ca(2+) alginate) dispersed suspensions were investigated under DC electric fields. A noteworthy result is that the Ca(2+) alginate dispersed suspension showed negative electrorheological effects under electric fields while the other suspensions exhibited positive electrorheological effects. It is the first time that the negative ER effect is obtained with the biomacromolecule. Interestingly, at the DC electric fields, the electromigration of particles to two electrodes was observed in the negative ER fluid, while the particles-bridges formed between two electrodes in the case of the positive ER fluid. In conclusion, the specific salt type of biomacromolecules could be suitable ER particles for negative ER suspension. We believe that our study can present a new way for the development of the biocompatible and eco-friendly negative ER fluids.


Safe and efficient transgene expression in rat hepatocytes induced by adenoviral administration into the biliary tract.
We examined whether retrograde intrabiliary adenoviral administration could induce safe and efficient transgene expression in hepatocytes. We administered recombinant adenovirus carrying a reporter lacZ gene retrogradely into the common bile duct of rats and evaluated the transduction efficiency of the lacZ gene in the liver histochemically by X-gal staining, and also quantitatively by a chemiluminescent reporter gene assay. Retrograde administration of adenovirus into the common bile duct was shown to successfully induce transgene expression in the liver. Although transgene expression induced by intrabiliary adenoviral administration was observed predominantly at periportal areas, a considerable number of cells expressing the transgene were detectable even in lobular and centrilobular areas. Furthermore, histochemical analysis revealed that intrabiliary adenoviral administration resulted in gene transfer into hepatocytes, but not into biliary epithelial cells. Transgene expression in the liver was transient, and pathological and biochemical analyses revealed that hepatic damage caused by intrabiliary adenoviral administration was not substantial. The results demonstrated in the present study suggest that retrograde administration of adenovirus into the common bile duct can induce safe and efficient transgene expression in hepatocytes without causing considerable adverse effects, supporting the feasibility of adenovirus-mediated gene transfer into hepatocytes in clinical settings by means of endoscopic retrograde cholangiography.


Risk Assessment Considerations for Genetically Modified RNAi Plants: EFSA's Activities and Perspective.
Genetically modified plants (GMPs) intended for market release can be designed to induce "gene silencing" through RNA interference (RNAi). The European Food Safety Authority (EFSA) and other international risk assessment bodies/regulatory agencies have taken several actions to determine whether the existing risk assessment approaches for GMPs are appropriate for the risk assessment of RNAi-based GMPs or require complementary or alternative approaches. To our knowledge, at the international level, no dedicated guidelines have been developed for the risk assessment and regulation of RNAi-based GMPs, confirming that existing science-based risk assessment approaches for GMPs are generally considered suitable for RNAi-based GMPs. However, some specificities have been identified for the risk assessment of RNAi-based GMPs. Here, we report on some of these specificities as identified and addressed by the EFSA GMO Panel for the molecular characterisation, food/feed safety assessment and environmental risk assessment of RNAi-based GMPs, using the DvSnf7 dsRNA-expressing maize MON87411 as a case study.


PEGylated murine Granulocyte-macrophage colony-stimulating factor: production, purification, and characterization.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) regulates proliferation, differentiation, and function of hematopoietic progenitor cells. Aside from expansion of hematopoietic cells, GM-CSF has shown efficacy in other diseases, including Crohn's disease. While GM-CSF being clinically used in humans, the ability to perform mechanistic studies in murine models is difficult due to the limited availability and rapid clearance of murine GM-CSF in the peripheral blood. To address these issues, we efficiently expressed murine GM-CSF under the control of the AOX1 gene promoter in Pichia pastoris using the Mut(S) strain KM71H. We describe the unique conditions that are required for efficient production by high-density fermentation and purification of mGM-CSF protein. Recombinant mGM-CSF protein was purified by tangential flow ultrafiltration and preparative reverse phase chromatography. To address limited half life or rapid clearance in mice, recombinant murine GM-CSF was modified by lysine-directed polyethylene glycol conjugation (PEGylation). PEG-modified and unmodified proteins were characterized by amino terminus sequence analysis and matrix assisted laser desorption ionization time-of-flight mass spectrometry. Under the mild reaction conditions, the recombinant protein is efficiently modified by PEGylation on an average of 2-3 sites per molecule. In vivo treatment of mice with PEGylated mGM-CSF, but not the unmodified recombinant mGM-CSF, reproduces the potent colony stimulating effects of human GM-CSF in patients on myeloid progenitor populations, as assessed by FACs analysis. This simplified approach for the expression, purification, and modification of a biologically potent form of murine GM-CSF should facilitate the study of central mechanisms of action in murine disease models.


Hospital Acquired Pathogenic Escherichia coli from Clinical and Hospital Water Samples of Quetta Balochistan.
A study was conducted to determine the prevalence and drug resistance of Escherichia coli present in urinary tract infected patients and hospital drinking water. A total of eighty urine samples from clinically suspected patients and thirty tap water samples from hospital vicinity were collected and analyzed for the presence of E. coli. The isolates were preliminary identified based on morphological characteristics, biochemical test and further confirmed by polymerase chain reaction (PCR) using uidA primer. Isolates were subjected to antibiogram studies and analyzed for the presence of drug resistance (ESBL blaCTX-M-15, tetA, and TMP-SMX dfrA1) and pathogenicity associated pyelonephritis-associated pili (PAP) and Heat-labile (LT) toxin genes. Urine samples 19/80 (23.75%) and water samples 8/30 (26.7%) were found contaminated with E. coli. It was found that 12/19 (63%) bacterial isolates were extended spectrum beta-lactamase (ESBL) producers in clinical and 6/8 (75%) in water isolates whereas tetracycline resistance in clinical and water isolates was 11/19 (58%) and 6/8 (75%), respectively. The trimethoprim resistance gene was confirmed in 12/19 (63%) in clinical and 2/8 (25%) in water isolates. All the clinical and water isolates were found carrying pili PAP gene. It was concluded that the presence of drug resistant and pathogenic E. coli in clinical and water samples is extremely alarming for public health due to cross contamination and bacterial transfer from clinical samples to water and vice versa.


The occurrence of a phosphorylated glycosphingolipid in Aspergillus niger.
A novel type of water-soluble phosphorylated glycosphingolipid was isolated from Aspergillus niger by a simple procedure involving precipitation, DEAE-cellulose chromatography and preparative t.l.c. Besides ceramide and phosphorus it contains inositol, galactose, mannose and small amounts of glucosamine.


Glucocorticoid-regulated genes in eosinophilic esophagitis: a role for FKBP51.
Eosinophilic esophagitis (EE) involves marked accumulation of eosinophils in the esophageal mucosa that responds to swallowed fluticasone propionate (FP) in a subset of patients. We aimed to uncover the mechanism of action of swallowed FP in patients with EE by providing evidence for a topical effect in the esophagus by identifying a molecular signature for FP exposure in vivo. Global microarray expression profiles, immunofluorescence microscopy, and cell signaling in esophageal tissue and cell lines were analyzed. Thirty-two transcripts exhibited altered expression in patients who responded to swallowed FP treatment. Esophageal FK506-binding protein 5 (FKBP51) mRNA levels were increased (P < .05) in FP responders compared with those seen in control subjects and patients with untreated active EE. After FP treatment of esophageal epithelial cells, FKBP51 mRNA and protein levels were increased in a dose- and time-dependent manner by FP treatment in vitro. FP-induced FKBP51 was steroid receptor dependent because RU486 completely inhibited gene and protein induction. The half-life of FKBP51 mRNA was 16 to 18 hours independent of FP treatment. FKBP51 overexpression reduced FP action as assessed by FP inhibition of IL-13-induced eotaxin-3 promoter activity. Our results suggest that swallowed glucocorticoid treatment directly affects esophageal gene expression in patients with EE. In particular, increased FKBP51 transcript levels identify glucocorticoid exposure in vivo and distinguish FP responders from untreated patients with active EE and patients without EE. In addition, FKBP51 reduces glucocorticoid-mediated inhibition of IL-13 signaling in epithelial cells in vitro, suggesting that FKBP51 might influence FP responsiveness. We propose that esophageal FKBP51 levels have diagnostic and prognostic significance in patients with EE.


Incontinence after lateral internal sphincterotomy: anatomic and functional evaluation.
This study was designed to evaluate the anatomic and functional consequences of lateral internal sphincterotomy in patients who developed anal incontinence and in matched controls. The study includes 13 patients with anal incontinence after lateral internal sphincterotomy and 13 controls who underwent the same operation and were continent and satisfied with the results of the procedure. Patients underwent clinical evaluation, anorectal manometry, pudendal nerve terminal motor latency testing, and endoanal ultrasonography. Sphincterotomies were longer in incontinent patients (75 vs. 57 percent), but the resting pressure and length of the high-pressure zone were not different between groups. Surprisingly, maximum voluntary contraction was higher in incontinent patients than in continent controls (136 vs. 100 mmHg). Rectal sensation and pudendal nerve terminal motor latency were similar in both groups. The defect in the internal sphincter was wider in incontinent patients than in continent controls (17.3 vs. 14.4 mm), but these differences were not statistically significant. The thickness of the internal sphincter measured by endoanal ultrasound was identical in both groups, but the external sphincter was thinner in incontinent patients both at the site of the sphincterotomy (6.8 vs. 8.1 mm) and in the posterior midline (7.1 vs. 8.6 mm). Anal incontinence after lateral internal sphincterotomy is directly related to the length of the sphincterotomy. Whether secondary to preoperative sphincter abnormality or the result of lateral internal sphincterotomy, the external sphincter is thinner in incontinent patients than in continent controls.


Post-LASIK Ectasia: Twenty Years of a Conundrum.
Corneal ectasia has emerged as a serious complication of laser vision correction (LVC) procedures since the first report by Seiler in 1998. Thereby, its prevention has become a major concern for refractive surgeons. Ectasia occurs due to biomechanical decompensation of the stroma, which may be related to a severe impact on corneal structure (i.e., attempted treatment for high myopia) or the altered biomechanical properties preoperatively. The current understanding is that a combination from those factors determines stability or ectasia progression after LVC. Abnormal corneal topography has been the most important surrogate for lower biomechanical properties, but novel imaging technologies such as tomography and biomechanical assessment have proven to enhance the ability for detecting mild ectatic disease, such as in the eyes with normal topography from patients with clinical ectasia in the fellow eye. Bohac and associates in a retrospective case series analyzed data from 30,167 eyes from 16,732 documented ten eyes (0.033%) of seven patients that developed post-LASIK ectasia. This data supports the concept that the actual incidence of ectasia has decreased from 0.66% reported by Pallikaris in 2001. This has been the result of major development related to the advanced screening strategies. Nevertheless, mysterious cases of ectasia still challenge the field and stimulated research in this field. Ocular allergy and eye rubbing may be a factor that triggered ectasia in such series. Artificial intelligence (AI) and machine-learning algorithms may play a definitive role for further enhancing ectasia risk assessment. Reporting ectasia after LVC is needed.


Extensive analysis of lymphocyte subsets in normal subjects by three-color immunofluorescence.
In the present work, 30 normal controls were studied with 11 combinations of 3 monoclonal antibodies in order to define CD20, CD4, CD8, CD16 and CD56 subsets as well as their activation status. Our results indicated that among B cells, CD5- cells predominated (about 92%), the minor CD5+ fraction showed variations between individuals but sometimes was as high as 20% in B cells; the CD45RA+CD29- subset (naive cells) accounted for 31.56 +/- 10.03% in CD4 cells, as compared to CD4+CD29+CD45RA- (memory cells) (46.54 +/- 10.35%), while CD4+CD29+CD45RA+ (transition cells between naive and memory state) represented 9.6 +/- 5.3% as compared to double-negatives (12.3 +/- 5.24%). Some uncertainties persist in defining CD8 subsets. NK CD8 cells accounted for about 20% of total CD8 according to CD16 and CD56 expression. Cytotoxic T lymphocytes could be delineated by S6F1 (76.22 +/- 11.28% within CD8 cells), though this marker appeared to be expressed by both cytotoxic and NK cells. Phenotypic definition of suppressive CD8 cells remains uncertain despite the fact that suppressor activity was found among CD8 lymphocytes expressing CD11b and probably CD57. NK cells coexpressed CD16 and CD56 markers in about 5% of all lymphocytes, while NK cells expressing CD16 alone accounted about 6%. Exclusive expression of CD56 was found in about 5%. Finally, while activated cells characterized by DR expression represented about 4% of CD4 and 9% of CD8 cells, CD25 appeared to be poorly represented among CD4, CD8 and CD20.(ABSTRACT TRUNCATED AT 250 WORDS)


Pharmacokinetic modelling of the anti-malarial drug artesunate and its active metabolite dihydroartemisinin.
A four compartment mechanistic mathematical model is developed for the pharmacokinetics of the commonly used anti-malarial drug artesunate and its principle metabolite dihydroartemisinin following oral administration of artesunate. The model is structurally unidentifiable unless additional constraints are imposed. Combinations of mechanistically derived constraints are considered to assess their effects on structural identifiability and on model fits. Certain combinations of the constraints give rise to locally or globally identifiable model structures. Initial validation of the model under various combinations of the constraints leading to identifiable model structures was performed against a dataset of artesunate and dihydroartemisinin concentration-time profiles of 19 malaria patients. When all the discussed constraints were imposed on the model, the resulting globally identifiable model structure was found to fit reasonably well to those patients with normal drug absorption profiles. However, there is wide variability in the fitted parameters and further investigation is warranted.


Morphological and histological investigation of the conduction system in the equine atrial muscle sleeve of pulmonary veins.
Atrial fibrillation is the most common arrhythmia in horses causing poor performance. The role of pulmonary vein triggers in the pathogenesis has been identified in horses. Ablation methods have been investigated, but the available information on anatomical, histological and immunohistochemical assessment of the pulmonary vein ostia and the conduction system of the myocardial sleeve is still limited. The aim of the study was to describe the morphological properties of the myocardial sleeve in healthy horses. Cross-sectional. Eighty-three equine hearts were dissected. The number and diameters of pulmonary vein ostia were determined, and anatomical localisation was described. Fifty-eight tissue samples were collected for routine histology and 12 of these were used for immunohistochemistry (connexin 43, 45, S100, and tyrosine hydroxylase antibodies). The mean number of pulmonary vein ostia was 4.5 (4 veins: 46 horse, 5 veins: 31 horses, 6 veins: 6 horses). Diameters (mean ± SD) of the main ostia were as follows: vein I: 20.2 ± 7.0 mm, vein II: 32.7 ± 7.1 mm, vein III: 33.4 ± 5.9 mm, vein IV: 18.1 ± 4.5 mm. Diameters of supernumerary vein ostia varied between 3.0 and 28.0 mm (11.5 ± 5.5 mm). Early branching was found in 26 horses (31.3%) and 30 veins (vein I: 14, vein II: 9, vein III: 5, vein IV: 2). Histology confirmed the presence of a muscle sleeve composed of myocardial tissue in each pulmonary vein. S100 and TH positivity was detected in each vein, and it confirmed the presence of adrenergic and non-adrenergic nerve fibres within the myocardial sleeve. Cx43 and 45 positivity were also found in each vein indicating the presence of gap junctions. The effect of bodyweight on pulmonary vein dimensions is unknown. Future ablation techniques should consider that conductive tissue is present in the entire myocardial sleeve in all pulmonary vein ostia.


Tracheal and bronchial obstruction following cyanoacrylate aspiration in a toddler.
Cyanoacrylates are a common class of household substances used as adhesives and are commonly sold under brand names such as Super Glue, Krazy Glue, and others. We are reporting a case of accidental cyanoacrylate adhesive aspiration by a toddler complicated by tracheal and bronchial obstruction. A toddler ingested a low-viscosity cyanoacrylate product and developed a severe, persistent cough. Initial vital signs, oxygen saturation, lung sounds, and chest radiograph were unremarkable. Rigid bronchoscopy was performed and several pieces of glue were removed from both main stem bronchi. The child made a full recovery after a 10-day hospital stay. Cyanoacrylate ester polymers are hard, glassy resins that exhibit excellent adhesion to a variety of materials. Aspiration of these products is a poorly described clinical entity. The low viscosity of cyanoacrylate adhesive formulations makes aspiration of these products a rare but potentially life-threatening exposure. Management centers upon supportive care and consideration of rigid bronchoscopy for removal of adherent glue.


Rapid and specific electrochemical detection of prostate cancer cells using an aperture sensor array.
A rapid, simple and specific cancer cell counting sensor would allow for early detection and better disease management. We have developed a novel cell counting device that can specifically count 125 prostate cancer cells in both complex media with serum and a mixed cell population containing non-target cells within 15 min. The microfabricated glass chip with exposed gold apertures utilizes the anti-EpCAM antibody to selectively count prostate cancer cells via differential pulse voltammetry. The newly developed sensor exhibits excellent sensitivity and selectivity. The cells remain viable throughout the counting process and can be used for further analysis. This device could have utility for future applications in early stage cancer diagnosis.


TAK242 suppresses the TLR4 signaling pathway and ameliorates DCD liver IRI in rats.
Ischemia‑reperfusion injury (IRI) is a notable cause of tissue damage during surgical procedures and a major risk factor in graft dysfunction in liver transplantation. Livers obtained from donors after circulatory death (DCD) are prone to IRI and toll‑like receptor 4 (TLR4) serves a prominent role in the inflammatory response associated with DCD liver IRI. The present study was designed to investigate whether TAK242, a specific TLR4 inhibitor, improves hepatic IRI following a DCD graft and to investigate its underlying protective mechanisms. Male Sprague‑Dawley rats were randomized into 4 groups: Control, TAK242, DCD and DCD+TAK242 groups. Rats were pretreated with TAK242 or its vehicle for 30 min, then the livers were harvested without warm ischemia (control group and TAK242 group) or with warm ischemia in situ for 30 min. The livers were stored in cold University of Wisconsin solution for 24 h and subsequently perfused for 60 min with an isolated perfused rat liver system. Rat liver injury was evaluated thereafter. When compared with the DCD group, DCD livers with TAK242 pretreatment displayed significantly improved hepatic tissue injury and less tissue necrosis (P<0.05). Compared with DCD livers, mechanistic experiments revealed that TAK242 pretreatment alleviated mitochondrial dysfunction, reduced reactive oxygen species and malondialdehyde levels and inhibited apoptosis. Additionally, TAK242 significantly inhibited the IRI‑associated inflammatory response, indicated by the decreased expression of TLR4, interleukin (IL)‑1β, IL‑6 and cyclooxygenase 2 at the mRNA and protein levels (P<0.05). TAK242 ameliorates DCD liver IRI via suppressing the TLR4 signaling pathway in rats. The results of the present study have revealed that TAK242 pretreatment harbors a potential benefit for liver transplantation.


Quality and Effectiveness of a Pediatric Triage Training Program in a Guatemalan Public Hospital.
This study aimed to develop and implement an Emergency Triage Assessment and Treatment (ETAT) training program at a Guatemalan public hospital. Collaborators included Baylor College of Medicine/Texas Children's Hospital, the Guatemalan Ministry of Health, and the Pan American Health Organization. The ETAT is a World Health Organization program to teach pediatric assessment, triage, and initial management to health care workers in resource-limited settings. The Baylor College of Medicine/Texas Children's Hospital created ETAT training materials in Spanish (Clasificación, Evaluación y Tratamiento de Emergencias Pediátricas [CETEP]) and conducted a train-the-trainer course for Hospital Nacional Pedro Bethancourt (HNPB) health care leadership. The HNPB subsequently conducted local trainings using a modified curriculum. Midcourse modifications based on evaluations and focus groups included distribution of manuals before training and an adding a day to the course.Course quality was assessed using participant evaluations and comparing pretest and posttest scores. Effectiveness was defined as 90% concordance between triage levels assigned by participants and facilitators. A total of 249 health care workers were trained by 24 HNPB facilitators. Mean pretest and posttest scores were 55 and 70, respectively (P < 0.001). On a 4-point scale, participants rated overall course quality and effectiveness as 3.6. Mean pretest (49 vs 58, P = 0.002) and posttest scores (68 vs 72, P = 0.01) improved for groups trained after modifications, as did evaluations for course quality (3.4 vs 3.7, P < 0.001) and effectiveness (3.4 vs 3.8, P < 0.001). Triage levels were assigned with 95% concordance (confidence interval, 91.9-97.3) between participants and facilitators. Hospital Nacional Pedro Bethancourt experts conducted high-quality trainings with locally relevant CETEP (ETAT) material. Trainings were effective and well received. The pediatric emergency department at HNPB now uses a triage system based on CETEP (ETAT).


Trends in Diagnostic Imaging by Nonphysician Practitioners and Associations With Urbanicity and Scope-of-Practice Authority.
We aimed to assess the changing share of diagnostic imaging billed by NPPs and how such changes differ by urbanicity within the context of scope-of-practice (SOP) regulations and legislation. This retrospective cohort study used patient claims for diagnostic imaging studies spanning 2016-2020 from Optum Clinformatics Datamart datasets. Multivariable modeling determined the odds of patients receiving NPP-interpreted vs physician-interpreted imaging. Imaging rates and trends in proportions of NPP-billed claims were assessed by urbanicity and relative to other factors including SOP, imaging modality, and place of service. Of all identified imaging claims, 3,348,881 (3.0%) were attributed to NPPs, with the highest rates of NPP interpretations per 10,000 images occurring in rural and small-town areas. From 2016 to 2020, the rate of NPP-billed imaging increased from 257 to 331 claims per 10,000 beneficiaries (P = 0.004), observed across both metropolitan (240 to 315, P = 0.001) and micropolitan (367 to 436, P = 0.020) settings. Although rates in rural and small-town areas rose, the increase was not significant (330 to 392, P = 0.363). Rises in NPP imaging in metropolitan settings occurred in states with moderately restrictive (307 to 358, P = 0.008) and least restrictive (289 to 419, P = 0.004) SOP legislation. Rates of diagnostic imaging interpretation by NPPs are rising. Growth in recent years appears driven by metropolitan areas in states with less restrictive SOP regulations. Future work is necessary to assess the quality of and downstream costs related to increasing NPP-interpreted imaging.