Effect of ethanol and some alcoholic beverages on gastric emptying in humans.
There is a paucity of detailed and controlled studies on the action of ethanol and alcoholic beverages on gastric emptying in humans. This study was designed to compare the effect of beer, red wine, whisky and their comparable pure ethanol solutions on gastric emptying in a controlled and randomized investigation. On separate days, 10 healthy, fasted subjects received the following solutions, in random order, through a gastric tube: 500 mL beer, red wine, comparable pure ethanol solutions (4% and 10% v/v), glucose (5.5% and 11.4% w/v) and water, 125 mL whisky and 40% (v/v) ethanol (both followed by 125 mL water) and 250 mL water. Gastric emptying of the test solutions was assessed using ultrasonography of the antrum. As measured by ultrasonography of the antrum, half emptying times of the ethanol solutions (4%, 10% and 40% v/v) were significantly (P < 0.05) longer (22.6 +/- 4.8, 22.7 +/- 4.3 and 27.8 +/- 3.3 min, respectively, n=10) than those of water (14.6 +/- 1.9 min (500 mL) and 13.2 +/- 1.7 min (250 mL), respectively). The half emptying times of beer (39.3 +/- 4.3 min) and red wine (72.6 +/- 7.6 min) were significantly longer than those of the corresponding ethanol concentrations, whereas whisky was emptied at nearly the same rate (26.4 +/- 5.9 min) as 40% (v/v) ethanol. Emptying of glucose 5.5% and 11.4% (w/v) was significantly and dose dependently slower (29.7 +/- 4.5 and 64.8 +/- 8.9 min) than water. 1) Pure ethanol in concentrations of 4%, 10% and 40% (v/v) inhibits gastric emptying. 2) The inhibitory effect of beer and red wine, but not of whisky, is stronger than that of their comparable ethanol concentrations. 3) Caloric content and non-alcoholic ingredients in alcoholic beverages produced by fermentation (beer and wine), but not in those produced by distillation (whisky), are most likely responsible for this effect.


Omeprazole and Helicobacter pylori: temporary suppression rather than true eradication.
Twenty-four Helicobacter pylori (H. pylori)-positive patients were treated for 28 days with either 20 mg omeprazole o.m. (n = 12) or 40 mg omeprazole o.m. (n = 12). Clearance (absence of H. pylori at the end of or shortly after treatment) and eradication (absence of H. pylori 1 month after cessation of treatment) were assessed using the 14C-urea breath test. Observed clearance and eradication were: 20 mg omeprazole 3/12 and 0/12; 40 mg omeprazole 6/12 and 1/12 respectively. The effect on H. pylori is probably due to the change in gastric pH from acid to neutral, however it is insufficient to recommend the inclusion of omeprazole in regimens aimed at eradicating H. pylori.


[Empty sella syndrome in childhood].
6 cases of the primary empty sella syndrome, 5 boys and 1 girl aged from 1 to 22 years, are being treated. The patients became suspicious due to a deficiency of pituitary hormones, whereby a lack of growth hormone was most common. 5 patients were short of growth; in provocative tests all 6 children showed either a partial or a complete deficiency of growth hormone. 2 patients had secondary hypothyroidism, 2 hypogonadotropic hypogonadism. Sceletal maturation was retarded between 2/12 and 4 4/12 years in all cases. All patients underwent a skull roentgenogram. An enlargement of the sella turcica was found in the case of one boy only. The findings of the other 5 children were inconspicious. For all patients the diagnosis was testified by a cranial computer-tomography.


Persubstituted cyclodextrin-based glycoclusters as inhibitors of protein-carbohydrate recognition using purified plant and mammalian lectins and wild-type and lectin-gene-transfected tumor cells as targets.
Multivalent glycoclusters have the potential to become pharmaceuticals by virtue of their target specificity toward clinically relevant sugar receptors. Their application can also provide fundamental insights into the impact of two spatial factors on binding, i.e., topologies of ligand (branching mode, cluster presentation) and carbohydrate recognition domains in lectins. Persubstituted macrocycles derived from nucleophilic substitution of iodide from heptakis 6-deoxy-6-iodo-beta-cyclodextrin by the unprotected sodium thiolate of 3-(3-thioacetyl propionamido)propyl glycosides (galactose, lactose and N-acetyllactosamine) were prepared. The produced glycoclusters were first tested as competitive inhibitors in solid-phase assays. A plant toxin from mistletoe and an immunoglobulin G fraction from human serum were markedly susceptible. A nearly 400-fold increase in inhibitory potency of each galactose moiety in the heptavalent form relative to free lactose (217-fold relative to free galactose) was detected. Thus, these glycoclusters can efficiently interfere, for example, with xenoantigen-dependent hyperacute rejection. Among the tested galectins selected from this family of adhesion- and growth-regulatory endogenous lectins, the substituted beta-cyclodextrins acted as sensors to delineate topological differences between the two dimeric prototype proteins. The relatively strong reactivity with chimera-type galectin-3, a mediator of tumor metastasis, disclosed selectivity for glycocluster binding among galectins. Equally important, the geometry of ligand display (maxiclusters, bi- or triantennary N-glycans) made its mark on the inhibitory potency. To further determine the sensitivity of a distinct galectin presented on the cell surface and not in solution, we established a stably transfected tumor cell clone. We detected a significant response to presence of the multivalent inhibitor. This type of chemical scaffold with favorable pharmacologic properties might thus be exploited for the design of galectin- and ligand-type-selective glycoclusters.


[Treatment of hypertension in elderly patients].
Today indications for treatment of hypertension in older age are no longer contested, even if only systolic pressure is raised. The choice of the antihypertensive drug for elderly patients, however, depends on concomitant diseases. The diversity of the latter demands a judicious, individualized use of the available substances (diuretics, beta-blockers, calcium antagonists and ACE-inhibitors). In elderly patients as well, a marked reduction of the cardiovascular risk is achievable by pharmacotherapy. So far, however, such results have only been reported for the use of diuretics and beta-blockers, in purely systolic hypertension by diuretics exclusively; however smaller studies, suggest that comparably favorable results may be obtained with calcium antagonists.


Piety and the agnostic gay poet: Thom Gunn's biblical homoerotics.
Thom Gunn has relied on biblical stories throughout his writing career to carry gay-themed poems. Although he characterizes himself agnostic, it is difficult to reconcile this self-definition with the tenderness evident in his biblical poems, a tenderness that many would identify with a kind of piety. Two of these poems reflect Gunn's reaction to paintings by Caravaggio, "The Sacrifice of Isaac" and "The Conversion of St. Paul." For the former, Gunn seems to have intuited Caravaggio's fascination with the naked figure of Isaac who appears about to be sodomized by Abraham. For the Paul poem, Gunn chooses one of two Caravaggio paintings on the subject, the one which emphasizes Paul in a recumbent and vulnerable sexual position. Gunn has also written tenderly of the Virgin Mary and Christ. His poem "Lazarus Not Raised" is an unusual look at the New Testament Lazarus story from Lazarus's point of view as a dead man who is not particularly interested in coming back to life even though he is encouraged to do so by a bevy of male friends. In recent years Gunn has continued to use biblical flavors in his verse, maintaining all the time his agnosticism.


Phosphate binding by natural iron-rich colloids in streams.
Phosphorus (P) in natural waters may be bound to iron (Fe) bearing colloids. However, the natural variation in composition and P binding strength of these colloids remain unclear. We related the composition of "coarse colloids" (colloids in the 0.1-1.2 μm size range) in 47 Belgian streams to the chemical properties of the streamwater. On average, 29% of the P in filtered (<1.2 μm) samples of these streams is present in coarse colloids. The concentration of Fe-rich colloids in streams decreases with increasing water hardness and pH. The P bearing colloids in these streams mostly consist of Fe hydroxyphosphates and of Fe oxyhydroxides with surface adsorbed P, which is underpinned by geochemical speciation calculations. In waters with molar P:Fe ratios above 0.5, only a minor part of the P is bound to coarse colloids. In such waters, the colloids have molar P:Fe ratios between 0.2 and 1 and are, therefore, nearly saturated with P. Conversely, in streams with molar P:Fe ratios below 0.1, most of the P is bound to Fe-rich colloids. Equilibration of synthetic and natural Fe and P bearing colloids with a zero sink reveals that colloids with low molar P:Fe ratios contain mostly nonlabile P, whereas P-saturated colloids contain mostly labile P which can be released within 7 days. Equilibration at a fixed free orthophosphate activity shows that the Fe-rich colloids may bind only limited P through surface adsorption, in the range of 0.02-0.04 mol P (mol Fe)(-1). The P:Fe ratios measured in naturally occurring Fe and P bearing colloids is clearly higher (between 0.05 and 1). These colloids are therefore likely formed by coprecipitation of P during oxidation of Fe(II), which leads to the formation of Fe hydroxyphosphate minerals.


Scanning electron microscopy study of the adhesion of Prevotella nigrescens to the dentin of prepared root canals.
The purpose of this study was to evaluate the effect of the presence or absence of amorphous, irregular smear layers on the adhesion of Prevotella nigrescens, to the dentin of the root canal by using scanning electron microscopy (SEM). Human incisors extracted within 7 days, with no cavities, no fractures, and no evidence of calcification of the canal, were selected. After cutting the crown portion at the CEJ, root canal preparation was undertaken by using a modified crown-down technique with Profile and Gates Glidden drills. Ten milliliters of physiologic saline solution (groups 1 and 4), 10 ml of 3.5% NaOCl (groups 2 and 5), or 10 ml of NaOCl and 10 ml of 0.5 M EDTA (groups 3 and 6) were used as irrigation solution while preparing the canal. After vertical sectioning and ethylene oxide gas sterilization, samples (groups 1, 2, and 3) were immersed in brain-heart infusion broth with yeast extract, hemin, and menadione, inoculated with P. nigrescens (ATCC 33563), and incubated for 3 h at 37 degrees C. All samples were prepared for and observed with SEM. The data were analyzed by using t test and one-way ANOVA. Smear layer was observed to cover the entire root canal surface after root canal preparation. Smear layer was removed and the entrances of dentinal tubules opened widely after applying 3.5% NaOCl and 0.5 M EDTA. A significantly greater number of bacteria were found to adhere to those teeth in which a smear layer was present (p < 0.05). Given that the smear layer produced during root canal preparation promoted adhesion and colonization of P. nigrescens to the dentin matrix, it might also increase the likelihood of canal reinfection.


Successful treatment of HTLV-1-related overlap syndrome using tacrolimus.
A 56-year-old HTLV-I-positive woman, initially diagnosed as having Sjögren's syndrome, presented with muscle weakness, myalgia, face erythema and leg edema. Based on the presence of various autoantibodies, the diagnosis of overlap syndrome (dermatomyositis/Sjögren's syndrome) was made. Treatment with high-dose corticosteroid plus cyclosporine improved her symptoms. However, three months after the start of these treatments, exacerbation of myositis occurred. A muscle biopsy revealed prominent perivascular accumulation of mononuclear cells with perifascicular atrophy, which were consistent with dermatomyositis. Tacrolimus, which was substituted for cyclosporine led to marked improvement of the myositis symptoms.


Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease.
The autosomal recessive lpr and gld genes induce in mice multiple autoantibodies and the progressive accumulation of large numbers of non-malignant CD4- CD8- T lymphocytes. The clinical syndromes and immune abnormalities associated with these two nonallelic genes are nearly identical and are also highly dependent on background genes. MRL/lpr mice are particularly severely affected, and they develop a syndrome that is serologically and pathologically similar to human systemic lupus erythematosus (SLE). Abnormal cell marker expression in the aberrant lpr T lymphocytes includes surface antigens normally associated with activated T cells or even with B cells, and it occurs along with enhanced expression of certain oncogenes. The lpr gene results in intrinsic abnormalities of both T and B lymphocytes, yet its location and product are unknown. The gld gene is located on chromosome 1; its product is also unknown. Although many immunological abnormalities are known, the mechanism whereby these two genes induce autoimmunity and lymphoproliferation remains obscure. Further studies of mice bearing these mutant genes are certain to yield insights into systemic autoimmunity and the control of lymphocyte proliferation.


Interaction of heparin and protamine in presence of overdosage: in vitro study.
Heparin is used for anticoagulation during cardiopulmonary bypass. After weaning from bypass, protamine is administered to neutralize the effects of heparin and thus reestablish hemostasis. Rotational thrombelastometry has been shown to discriminate between heparin and other impairing effects on coagulation. We analyzed the interaction of heparin and protamine under different conditions of overdosage in an in-vitro trial. Blood samples were taken from 17 healthy volunteers, separated, and spiked in vitro with heparin, protamine for heparin neutralization, an overdosage of protamine, and two dosages of re-heparinization to evaluate heparin effects under the condition of protamine overdosage. All samples were analyzed in a standard ROTEM rotational thromboelastometry device after intrinsic activation with and without addition of heparinase. Coagulation time, maximum clot firmness, and clot formation time were recorded. Heparin led to prolongation of coagulation and clot formation times in the test without heparinase. Adequate protamine addition normalized the test, and overdosage of protamine led to significant prolongation of both times. Addition of heparin in the presence of protamine overdosage normalized these parameters. We reconfirmed that the ROTEM device enables discrimination of the effects heparin and protamine on coagulation and detection of the coagulation-impairing effects of protamine overdosage. Furthermore, we were able to show a positive effect on coagulation times by heparin in the presence of protamine overdosage. Because this was an in-vitro study, these findings need to be confirmed in vivo, requiring further research.


Nuclear receptor agonists stimulate release of arachidonic acid from rat liver cells.
Release of arachidonic acid (AA) from rat liver cells is stimulated after a 6 h incubation with compounds that are members of the nuclear receptor superfamily, including vitamin D(3), clofibrate, 22(R) OH cholesterol, farnesol, progesterone, testosterone, 17beta-estradiol, hydrocortisone, 3,3'5 triiodothyronine, juvenile hormone III, WY14643, L -thyroxine, the tyrosine analog of thiazolidinediones, GW7845, tamoxifen, hydroxytamoxifen, 17alpha-estradiol and D -thyroxine. Squaline, lanosterol, cholesterol and the 17beta-estradiol antagonist, ICI-182,780, do not stimulate. ICI-182,780 inhibits the release stimulated by 17beta-estradiol, vitamin D(3), 22(R) OH cholesterol, celecoxib or indomethacin. Actinomycin D abolishes the release stimulated by 15-deoxy-delta(12,14) PGJ(2), but is less effective at inhibiting the release stimulated by all of the agonists listed above as well as the release stimulated by 9-cis retinoic acid, all trans -retinoic acid, the thiazidinedione, ciglitazone and the non-steroidal anti-inflammatory drugs, indomethacin and celecoxib. Based on the effects of the 17beta-estradiol antagonist, ICI-182,780, the release of AA appears to be a membrane effect and may not be mediated by the classical estrogen receptors. From the results obtained with actinomycin D, some stimulations may require transcription.


Strain and strain rate echocardiography.
Strain and strain rate echocardiography is an emerging technique for assessing myocardial systolic and diastolic function. It is envisioned that this modality could change the quantitative assessment of regional wall motion and improve the accuracy and reproducibility of test readings. Myocardial strain and strain rate can detect inducible ischemia and at earlier stages than visual estimation of wall motion or wall thickening parameters. Changes in systolic strain rate and strain have potential to discriminate between different myocardial viability states. Measurement of diastolic rate of deformation can differentiate physiologic from pathologic hypertrophy, and restrictive from constrictive cardiomyopathy. This article reviews basic principles and current experimental and clinical applications of strain and strain rate echocardiography.


The relationship among child weight status, psychosocial functioning, and pediatric health care expenditures in a medicaid population.
To examine the association between weight status and health service use, while considering the influence of psychosocial functioning and demographic variables. Two hundred child-parent dyads were recruited from pediatric primary care clinics and completed measures of height, weight, and questionnaires assessing psychosocial functioning. Claims and expenditure data over a 12-month retrospective period were extracted from the Medicaid claims database. Children who were obese incurred greater health service use and expenditures than children who were of a healthy weight, even after controlling for psychosocial functioning and other demographic variables. Children who were overweight (but not obese) did not have differing levels of claims or expenditures than their healthy weight peers. Understanding the impact of pediatric obesity on long-term expenditures is critical. These results provide some indication of the financial savings that might be achieved if obese children were supported to achieve a healthier weight status.


[Comparative analysis of methods evaluating ergonomic risks].
The authors demonstrated appropriateness of some subjective methods evaluating strain in workers engaged into road building and determined work hardiness categories, considering peculiarities of individual methods. Calculations using empiric equations covered energy consumption during workers' dynamic activities. Empiric equations were proved to point to higher energy consumption, if compared to results of experimental methods. Objective evaluation of work hardiness involved heart rhythm monitoring through a device transforming heart rate into metabolic energy, kcal/min.


Hybrid Quantum Dot Light-Emitting Diodes for White Emission Using Blue Phosphorescent Organic Molecules and Red Quantum Dots.
Hybrid quantum dot light-emitting diodes (QLEDs) with no buffer layer were developed to achieve white emission using red quantum dots by spin-coating, and blue phosphorescent organic molecules by thermal evaporation. These unique bichromatic devices exhibit two distinct electroluminescent peaks with similar intensities at 10.5 V. For white emission, these hybrid QLEDs present a maximum luminance of 6195 cd/m2 and a current efficiency of 2.02 cd/A. These results indicate that the unique double emission layers have the potential for bright and efficient white devices using fewer materials.


Aspirin for the Primary Prevention of Cardiovascular Disease: Time for a Platelet-Guided Approach.
Aspirin protects against atherothrombosis while increasing the risk of major bleeding. Although it is widely used to prevent cardiovascular disease (CVD), its benefit does not outweigh its risk for primary CVD prevention in large population settings. The recent United States Preventive Services Task Force guidelines on aspirin use to prevent CVD reflect this clinical tradeoff as well as the persistent struggle to define a population that would benefit from prophylactic aspirin therapy. Past clinical trials of primary CVD prevention with aspirin have not included consideration of a biomarker relevant to aspirin's mechanism of action, platelet inhibition. This approach is at odds with the paradigm used in other key areas of pharmacological CVD prevention, including antihypertensive and statin therapy, which combine cardiovascular risk assessment with the measurement of mechanistic biomarkers (eg, blood pressure and LDL [low-density lipoprotein]-cholesterol). Reliable methods for quantifying platelet activity, including light transmission aggregometry and platelet transcriptomics, exist and should be considered to identify individuals at elevated cardiovascular risk due to a hyperreactive platelet phenotype. Therefore, we propose a new, platelet-guided approach to the study of prophylactic aspirin therapy. We think that this new approach will reveal a population with hyperreactive platelets who will benefit most from primary CVD prevention with aspirin and usher in a new era of precision-guided antiplatelet therapy.


Capecitabine inhibits epithelial-to-mesenchymal transition and proliferation of colorectal cancer cells by mediating the RANK/RANKL pathway.
Colorectal cancer (CRC) is the third most prevalent malignancy globally. Capecitabine is an important form of chemotherapy for colorectal cancer. The present study aims to investigate the underlying mechanism of action of the drug in CRC cells. In the present study, 50 pairs of CRC and adjacent normal tissues were collected, and CRC cell lines (SW480, SW620, HT29, LOVO and HCT116) and NCM460 colonic epithelial cells were also purchased and used. Western blotting was used to measure the expression levels of proteins involved in the receptor activator of nuclear factor-κB (RANK)/receptor activator of nuclear factor-κB ligand (RANKL) pathway and epithelial-to-mesenchymal transition (EMT), including RANK, RANKL, osteoprotegerin (OPG), E-cadherin, vimentin and N-cadherin. Proliferation and migration were measured using MTT, Cell Counting Kit-8, EdU, Transwell and wound healing assays, respectively. In the present study, it was found that the RANK/RANKL pathway was activated in cancer tissues and cells. Additionally, it was observed that capecitabine treatment reduced the protein expression of RANK, RANKL and OPG in HT29 cells, suggesting that capecitabine has a repressive effect on the RANK/RANKL pathway. Furthermore, functional experiments revealed that the proliferative ability and the EMT process observed in HT29 cells were inhibited after they were treated with capecitabine or transfected with si-RANK. Rescue assays were then performed, which revealed that the promotion of RANK via transfection of cells with 50 nM pcDNA3.1-RANK reversed the inhibitory effects of capecitabine on HT29 cell proliferation and EMT. These findings suggest that the regulatory role of capecitabine is at least partially mediated through the RANK/RANKL pathway in colorectal cancer. The present study demonstrated that capecitabine-induced repression of CRC is exerted by inhibiting the RANK/RANKL pathway, where this new mechanism potentially provides a novel therapeutic target.


Detection of Mycobacterium tuberculosis and rifampicin resistance by Xpert® MTB/RIF assay among presumptive tuberculosis cases at Jimma University Medical Center, Southwest Ethiopia.
Rapid diagnosis of tuberculosis (TB) and detection of drug resistance are very important for timely and appropriate management of patients. Xpert MTB/RIF assay is approved for use in TB and rifampicin-resistance diagnosis. However, data are limited on the impact of Xpert MTB/RIF assay under routine clinical settings with a heterogeneous group of patients and sample types in Ethiopia. A retrospective study was carried out in 2220 presumptive TB cases at Jimma University Medical Center. Data were gathered from the registration logbook using formatted data extraction tools and double entered to epidata version 3.1 and further transported to SPSS version 20 for analysis. Associations were determined using the Chi-square test and P-value <0.05 was considered statistically significant. Of 2220 cases enrolled, 1665 (75%) were adults and the remaining 555 (25%) were children aged less than 14 years. The majority, 1964 (88.46%), had pulmonary manifestation and 256 (11.54%) had extrapulmonary involvements. The overall, frequency of Mycobacterium tuberculosis (MTB) was 9.3% (206/2220), among this 10.27% (171/1665) and 6.3% (35/555) were adults and children, respectively. M. tuberculosis was detected from 171 (8.75%) of pulmonary patients and 35 (13.28%) of extrapulmonary manifested patients. Out of 206 M. tuberculosis positive cases, 7(3.4%) were rifampicin-resistant: four from pulmonary tuberculosis (PTB) patients and three from EPTB patients. In the Chi-square test, the age group of 15-24 years, previous history of TB, pus/lymph node sample, and being HIV positive were significantly associated with TB positivity by Xpert MTB/RIF (P-value <0.001). These data suggest that the overall frequency of M. tuberculosis and rifampicin resistance was found to be relatively low compared to the previous reports in Ethiopia. Nevertheless, better diagnostic tools and approaches are still vital to halt the burden of TB and drug-resistant TB in the country.


Infrequent alterations of the p15, p16, CDK4 and cyclin D1 genes in non-astrocytic human brain tumors.
While several genetic alterations associated with the evolution of the astrocytomas have been identified, the molecular basis of non-astrocytic brain tumors has remained largely unknown. In this study, p15, p16, CDK4 and cyclin D1 genes were analyzed in 69 nonastrocytic human brain tumors, including 17 oligodendrogliomas, 16 medulloblastomas/primitive neuroectodermal tumors (PNETs), 14 ependymomas and 22 meningiomas. Southern blot analysis of DNA from frozen samples showed no homozygous deletions in p15 or p16 genes in any of these tumors. No mobility shift was found by PCR-single-strand conformation polymorphism (PCR-SSCP) analysis in exons 1 and 2 of the p15 gene and exons 1 and 2 of the p16 genes, except for one oligodendroglioma. Direct sequencing of DNA from this tumor showed a G --> A transition at nucleotide 436 (codon 140) in exon 2 of the p16 gene, which is a common polymorphism. Southern blot analyses revealed no amplification of CDK4 and cyclin D1 genes in any of the neoplasms analyzed. In contrast to astrocytic brain tumors, which show frequent loss of the p16 gene and amplification of the CDK4 gene, alteration of these genes appears to be rare in other neoplasms of the human nervous system.


Dosage of neuromuscular electrical stimulation: is it a determinant of upper limb functional improvement in stroke patients?
To investigate the predictors related to upper extremity functional recovery, with special emphasis on neuromuscular electrical stimulation dose-response in patients after stroke. Ninety-five patients with stroke who received a 4-week neuromuscular electrical stimulation intervention. Prospective predictive analysis. The change score of the Action Research Arm Test (ARAT) was used as the main outcome. Baseline subject characteristics, stroke-related data, and intervention-related data were collected. Multiple linear regression analysis was applied to identify the potential predictors related to main outcome. The regression model revealed that the initial Fugl-Meyer upper limb score was the most important predictor for ARAT change score post-test, followed by time since stroke onset and location of stroke lesion. At 2-month follow-up, the neuromuscular electrical stimulation dosage became a significant determinant in addition to the above predictors. Initial motor severity and lesion location were the main predictors for upper limb functional improvement in stroke patients. Neuromuscular electrical stimulation dosage became a significant determinant for upper limb functional recovery after stroke at 2-month follow-up. More intensive neuromuscular electrical stimulation therapy during early rehabilitation is associated with better upper limb motor function recovery after stroke.


Attenuation by atenolol of myocardial acidosis during ischemia in dogs: contribution of beta-1 adrenoceptors to myocardial acidosis.
Coronary artery occlusion produces myocardial acidosis, which can be attenuated by propranolol or sotalol. The present study was undertaken to determine which beta adrenoceptors, beta-1 or beta-2, contribute to the ischemic myocardial acidosis. Dogs anesthetized with pentobarbital were used. In the first series of experiments, blood flow in the left anterior descending coronary artery was reduced by an occluder to about one-third of the original flow. Myocardial pH was measured by means of a micro pH electrode inserted into the left anterior descending coronary artery area at the depth of about 8 mm. The myocardial pH decreased from 7.44 to 7.55 to 6.73 to 6.89, 30 min after partial occlusion being the time immediately before an i.v. injection of drugs. Atenolol (1 mg/kg) attenuated significantly the decrease in myocardial pH that had been induced by partial occlusion, whereas IPS 339 (360 micrograms/kg) and ICI 118,551 (300 micrograms/kg) did not. The pH effect of atenolol was confirmed even in the paced heart. In the second series of experiments, the antagonistic action of these drugs on the isoproterenol-induced increase in heart rate and myocardial contractile force and the decrease in diastolic blood pressure was investigated. By this experiment, it was confirmed that atenolol has the beta-1 adrenoceptor antagonistic action, and the IPS 339 and ICI 118,551 have the beta-2 antagonistic action. These results suggest that the activation of beta-1 adrenoceptors contribute to the myocardial acidosis during ischemia.


Association of frailty with regional sagittal spinal alignment in the elderly.
The degenerative changes in the spine of the frail elderly gradually exacerbate the alignment of the spine as the degeneration progresses. This study was conducted to assess the relationship between frailty and spine sagittal alignment measured in terms of global, cervical, thoracic, and lumbo-pelvic parameters. In total, 101 patients aged 75 years and older hospitalized for spine surgery were prospectively enrolled. We evaluated spinal sagittal parameters by dividing them into global (C7 sagittal vertical axis [SVA] and T1 pelvic angle [T1PA]), cervical (the C2-7 Cobb angle, Jackson line, and C2-7 plumb line), thoracic (thoracic kyphosis [TK]), and lumbo-pelvic (pelvic tilt [PT] and pelvic incidence minus lumbar lordosis value [PI-LL]). Patient characteristics; the Fatigue, Resistance, Ambulation, Illness, Loss of Weight (FRAIL) scale; and sagittal spinal parameters were included in the analysis. Multiple regression analysis was performed to identify associations between the FRAIL scale and sagittal spinal parameters. The FRAIL scale showed correlations with global sagittal parameters (C7 SVA [β = 0.225, p = 0.029] and T1PA [β = 0.273, p = 0.008]) and lumbo-pelvic parameters (PT [β = 0.294, p = 0.004] and PI-LL [β = 0.323, p = 0.001). Cervical and thoracic parameters were not directly associated with the FRAIL scale. LL and PI-LL were associated with TK, and TK was associated with cervical parameters (the C2-7 Cobb angle, Jackson line and C2-7 plumb line). In conclusion, frailty status could be an important factor that influences sagittal spinal alignment in the elderly. In this study, it was found that frailty mainly affected the balance of lumbo-pelvic alignment, and consequently affected the balance of the whole spine.


In-group defense, out-group aggression, and coordination failures in intergroup conflict.
Intergroup conflict persists when and because individuals make costly contributions to their group's fighting capacity, but how groups organize contributions into effective collective action remains poorly understood. Here we distinguish between contributions aimed at subordinating out-groups (out-group aggression) from those aimed at defending the in-group against possible out-group aggression (in-group defense). We conducted two experiments in which three-person aggressor groups confronted three-person defender groups in a multiround contest game (n = 276; 92 aggressor-defender contests). Individuals received an endowment from which they could contribute to their group's fighting capacity. Contributions were always wasted, but when the aggressor group's fighting capacity exceeded that of the defender group, the aggressor group acquired the defender group's remaining resources (otherwise, individuals on both sides were left with the remainders of their endowment). In-group defense appeared stronger and better coordinated than out-group aggression, and defender groups survived roughly 70% of the attacks. This low success rate for aggressor groups mirrored that of group-hunting predators such as wolves and chimpanzees (n = 1,382 cases), hostile takeovers in industry (n = 1,637 cases), and interstate conflicts (n = 2,586). Furthermore, whereas peer punishment increased out-group aggression more than in-group defense without affecting success rates (Exp. 1), sequential (vs. simultaneous) decision-making increased coordination of collective action for out-group aggression, doubling the aggressor's success rate (Exp. 2). The relatively high success rate of in-group defense suggests evolutionary and cultural pressures may have favored capacities for cooperation and coordination when the group goal is to defend, rather than to expand, dominate, and exploit.


Close juxtapositions between luteinizing hormone-releasing hormone-immunoreactive neurons and corticotropin-releasing factor-immunoreactive axons in the human diencephalon.
Gonadal functions are modulated by corticotropin-releasing factor (CRF) in the rat via direct suppression of LH-releasing hormone (LHRH) release. Although there is evidence of direct morphological contacts between the LHRH and CRF-immunoreactive (-IR) structures in the rat hypothalamus, little is known about the morphological base of CRF-influenced LHRH release in man. Thus, we studied the distribution of the CRF-IR and LHRH-IR systems in the human diencephalon and revealed putative CRF-LHRH juxtapositions using double label immunohistochemistry. LHRH-IR cells were present mainly in the infundibular region and the medial preoptic area. CRF-IR neuronal structures were observed in the periventricular area, paraventricular nucleus, infundibular region, and median eminence. CRF-LHRH juxtapositions were found mainly in the infundibulum and median eminence. Few juxtapositions were detected in the medial preoptic area. In these regions, black diaminobenzidine/silver-labeled CRF-IR fibers abutted fusiform brown diaminobenzidine-labeled LHRH neurons, usually forming multiple contacts. Examination of semithin sections of these close associations with the aid of oil immersion revealed no cleft between CRF-IR nerve terminals contacting LHRH-IR structures. These findings suggest that the juxtapositions between the LHRH-IR and CRF-IR neurons may be functional synapses forming the morphological substrate of the CRF-controlled LHRH secretion. Moreover, the wide distribution of CRF-IR elements suggests that CRF controls other diencephalic functions as well.


The social service divide: service availability and accessibility in rural versus urban counties and impact on child welfare outcomes.
An empirical study of 75 counties in a state found that social services are more available and accessible in urban versus rural counties, signaling a need for public policy addressing service allocation. The study also found a relationship between the accessibility of intensive family preservation services and reentry into foster care, a child welfare outcome. Implications for achieving outcomes affecting safety, permanence, and well-being of children are discussed.


Application of New Energy Thermochromic Composite Thermosensitive Materials of Smart Windows in Recent Years.
Thermochromic smart windows technology can intelligently regulate indoor solar radiation by changing indoor light transmittance in response to thermal stimulation, thus reducing energy consumption of the building. In recent years, with the development of new energy-saving materials and the combination with practical technology, energy-saving smart windows technology has received more and more attention from scientific research. Based on the summary of thermochromic smart windows by Yi Long research groups, this review described the applications of thermal responsive organic materials in smart windows, including poly(N-isopropylacrylamide) (PNIPAm) hydrogels, hydroxypropyl cellulose (HPC) hydrogels, ionic liquids and liquid crystals. Besides, the mechanism of various organic materials and the properties of functional materials were also introduced. Finally, opportunities and challenges relating to thermochromic smart windows and prospects for future development are discussed.


Parameter free evaluation of SN2 reaction rates for halide substitution in halomethane.
We estimate the kinetic constants of a series of archetypal SN2 reactions, i.e., the nucleophilic substitutions of halides in halomethane. A parameter free, multiscale approach recently developed [Campeggio et al., Phys. Chem. Chem. Phys., 2020, 22, 3455] is employed. The protocol relies on quantum mechanical calculations for the description of the energy profile along the intrinsic reaction coordinate, which is then mapped onto a reaction coordinate conveniently built for the reactive process. A Kramers-Klein equation is used to describe the stochastic time evolution of the reaction coordinate and its velocity; friction is parameterized using a hydrodynamic model and Kramers theory is used to derive the rate constant of the reaction. The method is here applied to six SN2 reactions in water at 295.15 K, which differ in the nucleophile and the leaving group. The computed reaction rates are in good agreement with the experimental data and correlate well with the trends observed for the activation energies.


9-(2-Hy-droxy-6-oxocyclo-hex-1-en-1-yl)-2,3,4,9-tetra-hydro-1H-xanthen-1-one.
In the xanthene ring system in the title compound, C19H18O4, the 4H-pyran ring has a maximum deviation of 0.110 (2) Å from planarity and the cyclo-hexene ring exhibits a puckered conformation [puckering parameters Q T = 0.452 (3) Å, θ = 57.0 (4) and ϕ = 131.7 (4)°]. The cyclo-hexene ring attached to the xanthene system adopts an envelope conformation, with the middle of the three methylene C atoms as the flap atom. In the crystal, O-H⋯O and C-H⋯O hydrogen bonds form infinite chains of R 1 (2)(6) ring motifs along [100] with the xanthene groups arranged in an alternating zigzag manner.


Recent advances in the application of CE to forensic sciences, an update over years 2009-2011.
The present article reviews and comments the applications of capillary electrophoresis in the different areas of forensic sciences covering the time from the second half of 2009 until the first part of 2011, being the latest update of previous reviews covering the years from 2001 to 2009. Numerous articles reporting applications of capillary electrophoresis to analytical problems of potential interest for the forensic researchers and scientists can be found in the most qualified journals of analytical chemistry, analytical biochemistry, pharmacology, toxicology, laboratory medicine, human genetics, etc. However, the present review has been focused on discussing only the most relevant examples of analytical applications of capillary electrophoretic and electrokinetic techniques published in the following fields: (i) illicit and abused drugs, (ii) ions and small molecules of forensic interest, (iii) proteins and peptides of forensic interest, (iv) dyes and inks, (v) forensic DNA. The present review collects and comments on 60 references.


Influence of direction of body weight change on pattern of gonadotropin secretion in ovariectomized beef heifers of equivalent body weight.
Our hypothesis was that alterations in pattern of gonadotropin secretion induced by level of dietary energy intake are dependent on direction of BW change. Beef heifers were assigned to one of two treatments 21 d after ovariectomy: 1) increasing followed by decreasing BW (I-D; n = 9) or 2) decreasing followed by increasing BW (D-I; n = 9). Heifers assigned to the I-D treatment received 15.4 Mcal ME/d (HE) from wk 0 to 8 followed by 4.3 Mcal ME/d (LE) from wk 9 to 16. Heifers assigned to the D-I treatment received the LE diet for the initial 8 wk followed by the HE diet for the subsequent 8 wk. At 2-wk intervals blood samples were collected at 10-min intervals for 11 h to determine the pattern of secretion and(or) concentration of gonadotropins in circulation (LH and FSH) and pituitary responsiveness to administration of 750 ng and 50 micrograms of LHRH. Frequency of LH pulses increased (P less than .05) in a quadratic fashion with increasing ADG in heifers in both treatment groups. Amplitude of LH pulses decreased (P less than .05) in a linear fashion with increasing ADG in heifers in both treatment groups and magnitude of this decline was greater (P less than .05) in heifers receiving the D-I treatment. Amplitude of response to 750 ng of LHRH decreased (P less than .05) in a linear fashion with increasing ADG in heifers receiving the D-I treatment but was unrelated to changes in ADG (P greater than .05) in heifers receiving the I-D treatment. When heifers in both treatment groups attained similar BW (P greater than .05; wk 14), amplitude of LH pulses, responsiveness to 750 ng of LHRH and mean concentration of FSH in serum were higher (P less than .05) in heifers receiving the I-D than in heifers receiving the D-I treatment. Thus, we accept the hypothesis that alterations in pattern of gonadotropin secretion in heifers fed diets with a low energy content are dependent on direction of BW change.


Simultaneous Detection of Multiple Salmonella Serovars from Milk and Chicken Meat by Real-Time PCR Using Unique Genomic Target Regions.
A novel genomic and plasmid target-based PCR platform was developed for the detection of Salmonella serovars Heidelberg, Dublin, Hadar, Kentucky, and Enteritidis. Unique genome loci were obtained through extensive genome mining of protein databases and comparative genomic analysis of these serovars. Assays targeting Salmonella serovars Hadar, Heidelberg, Kentucky, and Dublin had 100% specificity and sensitivity, whereas those for Salmonella Enteritidis had 97% specificity and 88% sensitivity. The limits of detection for Salmonella serovars Heidelberg, Kentucky, Hadar, Enteritidis, and Dublin were 12, 9, 40, 13, and 5,280 CFU, respectively. A sensitivity assay was also performed by using milk artificially inoculated with pooled Salmonella serovars, yielding a detection limit of 1 to10 CFU/25 mL of milk samples after enrichment. The minimum DNA detected using the multiplexed TaqMan assay was 75.8 fg (1.53 × 101 genomic equivalents [GE]) for Salmonella Heidelberg, 140.8 fg (2.8 × 101 GE) for Salmonella Enteritidis, and 3.48 pg (6.96 × 102 GE) for Salmonella Dublin. PCR efficiencies were 89.8% for Salmonella Heidelberg, 94.5% for Salmonella Enteritidis, and 75.5% for Salmonella Dublin. Four types of 30 pasteurized milk samples were tested negative by culture techniques and with a genus-specific Salmonella invA gene PCR assay. Among 30 chicken samples similarly tested, 12 (40%) were positive by both culture and the invA PCR. Testing of these 12 samples with the serovar-specific PCR assay detected single and mixed contamination with Salmonella Kentucky, Salmonella Enteritidis, and Salmonella Heidelberg. Five unique primers were designed and tested by multiplex conventional PCR in conjunction with the use of the multiplex TaqMan assay with three of the primers. The diagnostic assays developed in this study could be used as tools for routine detection of these five Salmonella serovars and for epidemiological investigations of foodborne disease outbreaks.


A consortium-based research education program for residents.
With growing pressures to consolidate and reorganize health care delivery systems, graduate medical education (GME) consortia can draw faculty from affiliated members to assemble educational programs. The authors report on consortium-based research education seminars of a quality that many residency programs would be unable to develop and support on their own. Drawing a diverse faculty from consortium members and area universities, the OHEP Center for Medical Education's annual Research Workshop Series focuses on the design of research projects; data analysis and hypothesis testing; and written and oral presentation of scientific research. Each spring, OHEP sponsors a research forum in which the best research projects from consortium members are presented by the resident-researchers, who compete for recognition and prize money. Further, of the 128 presentations made thus far at the annual OHEP Research Forum, 25% were subsequently published. The consortium's research education program has been well received by residents, is cost-effective, and is an integral component of the research curricula of many area residency programs. Including research training in GME provides residents an opportunity to become more competitive for fellowship, faculty, and leadership positions.


Spatial organization of neck and vestibular reflexes acting on the forelimbs of the decerebrate cat.
EMG recording was used to study the spatial organization of vestibular and tonic neck reflexes acting on forelimb and shoulder muscles of the decerebrate cat. Neck reflexes were studied in preparations with intact labyrinths as well as those with acute or chronic labyrinthectomies. Reflexes were described by response vectors whose orientation component is aligned with the optimal excitatory direction of tilt or head rotation. A muscle's vector orientation remained reasonably stable over a period of hours, although there was sometimes drift at the beginning or end of an experiment. Orientation of muscle response vectors did not change systematically with stimulus frequency of 0.05-2.0 Hz. For vestibular reflexes this is so, although their dynamics are consistent with convergent input from semicircular canals and otolith organs. Regardless of the preparation, a consistent reflex pattern emerged. Vestibular reflexes are characterized by response vector orientation near ear-down roll. Neck vector orientation lies in the opposite direction from the vestibular vector but typically lies further from the roll plane: Nose-up pitch is excitatory for the shoulder muscles supra- and infraspinatus, and for the medial and lateral heads of triceps, whereas nose-down pitch excites the long head of triceps. Our results generally agree with the pattern proposed by Roberts (28) for neck reflexes but disagree in part with his proposed pattern of vestibular reflexes; we did not see the expected consistent excitation by nose-down pitch.


Nursing, unionization, and caste: the lessons of local 6456.
A recent union drive by the faculty at the University of Illinois at Chicago sparked controversy among academic nurses in the College of Nursing. Background on the union drive and the history of nursing labor organizing is provided to demonstrate the fit of union representation for nurses in all settings today, including academia.


Effects of Quality, Intensity, and Duration of Light Breaks during a Long Night on Dormancy in Blue Spruce (Picea pungens Engelm.) Seedlings.
Blue spruce (Picea pungens Engelm.) seedlings grow continuously when exposed to photoperiods exceeding 16 hours and enter dormancy within 4 weeks under photoperiods of 12 hours or less. Dormancy was prevented under 12-hour photoperiods by 2-hour light breaks of red light (1.70 muw/cm(2) at 650 nm) or high intensity white light (2,164.29 muw/cm(2) at 400 to 800 nm) given in the middle of the 12-hour night, and by continuous low intensity white light (204.76 muw/cm(2) at 400 to 800 nm). Two-hour light breaks of far red light (1.80 muw/cm(2) at 730 nm), red light followed by far red light, or low intensity white light were not effective in delaying dormancy. The results imply that the phytochrome system mediates the photoperiodic control of dormancy in blue spruce seedlings. The similarity of results obtained using the low intensity, long duration as against the high intensity, short duration light treatments suggests that the law of reciprocity applies in this response.


Rationally Designed Three-Layered TiO2 @amorphous MoS3 @Carbon Hierarchical Microspheres for Efficient Potassium Storage.
Amorphous MoS3 has been an attractive electrode material for sodium-ion batteries and lithium-sulfur batteries. However, the potassium storage capability of amorphous MoS3 remains unreported. Herein, the construction of hybrid hierarchical microspheres composed of amorphous MoS3 nanosheets dual-confined with TiO2 core, and nitrogen-doped carbon shell layer (denoted as TiO2 @A-MoS3 @NC) via a self-templating method, combined with a low-temperature sulfurization process as a new anode material for potassium-ion batteries (PIBs), is reported. Benefitting from the unique structural merits including unique 1D chain structure, disordered arrangement of atoms and a large number of defects of amorphous MoS3 , more active heterointerfacial sites, effectively mitigated volume change, good electrical contact, and easy K+ ion migration, the TiO2 @A-MoS3 @NC microspheres exhibit excellent potassium-storage performance with high specific capacity, superior rate capability, and cycling stability.


Mucin in the dermis: a case of tender tumors.
We present an original case report of a 45-year-old woman with a five-month history of sporadic, tender, nodules present on the right upper abdomen, bilateral dorsal wrists, right upper arm, and left flank. Biopsy revealed a mild perivascular infiltrate, increased dermal mucin, and no significant increase in fibroblasts. Presentation and histology were most consistent with nodular lichen myxedematosus (NLM), a rare primary mucinosis. Only four previous cases are reported in the literature to our knowledge. Management of NLM and other subtypes of lichen myxedematosus is not well described. Our patient failed systemic steroids and was unable to tolerate hydroxychloroquine, but subsequently improved with oral methotrexate. This suggests that methotrexate may be of benefit for NLM.


The prognostic importance of BCR-ABL transcripts in Chronic Myeloid Leukemia: A systematic review and meta-analysis.
Chronic Myeloid Leukemia (CML) is characterized by the overproduction of BCR-ABL, a tyrosine kinase with constitutive activity, in which the majority of CML patients have e13a2 or e14a2 transcripts. Reckoned the possible associations between the hematologic and molecular features of the disease, a profound understanding of different aspects of this neoplasm would be provided. The authors implemented a systematic literature search, utilizing the terms published articles or internationally accepted abstracts from PubMed, Embase, Medline, Cochrane library before January 2019. Weighted mean proportion and 95 % confidence intervals (CIs) of CML prevalence calculated using a fixed-effects and a random-effects model. Statistical heterogeneity was evaluated using the I2 statistic. 34 studies for a total of 54,034 Patients were selected and included in the review. Results revealed that compared to e13a2 group, the overall estimated prevalence is much higher in the e14a2 (39 % and 54 %, respectively). Besides, the overall estimated prevalence ratio of male to female was higher in the e13a2 group in comparison to e14a2 (1.08 and 0.856 respectively). The overall estimated prevalence of dual transcription of e13a2/e14a2 was 1.11 %, and male/female overall estimated prevalence ratio was 1.18. This meta-analysis of CML patients demonstrated the e14a2 as the more common transcript type. Usually, the e14a2 transcript is prevalent in females, whereas e13a2 and dual transcription of e13a2/e14a2 are more common in men. These data explicate that the differences in proportion are not by chance. This is crucial, as the transcript type is a variable suspected to be of prognostic importance for the treatment-related response, the outcome of treatment, and the rate of treatment-free remission.


Recent developments in the epidemiology of epilepsy.
Epidemiological incidence data are important to determine those who are at risk of epilepsy and to understand the aetiology of the condition. A number of studies have been reported recently, which allow comparisons across populations. There appears to be geographical variation in the incidence of epilepsy, with a higher incidence in rural South America than in developed countries: no large scale incidence studies have yet been carried out in Africa or Asia. A consistent pattern suggesting that the onset of epilepsy occurs at the extremes of life has also been shown. Although a number of factors are often identified as causes of epilepsy, studies have identified a definitive aetiology in only one-third of all newly diagnosed cases. Epidemiological studies have, however, confirmed the importance of postnatal insults and quantified the risk. Family history may also be considered a risk factor for epilepsy in epidemiological terms.


Primary Aldosteronism: The Next Five Years.
The management of primary aldosteronism is widely varied within various published guidelines, with very little in the way of data supporting the choice of one variation over others. Current estimates of prevalence are probably accurate for aldosterone producing adenoma, but fall very short of that for bilateral adrenal hyperplasia. Discovery at the level of basic science has proven illuminating over the past 6 years in terms of unilateral disease and both somatic and germline mutations, with much less focus on the much more common bilateral disease; Attempts at harmonization have begun - for example, criteria for complete/partial/absent cure after adrenalectomy for unilateral disease; again focus on bilateral disease is muted. A number of possibilities are suggested as agenda for active consideration and change, across a wide range of areas - referral patterns, screening, confirmation and lateralization, what will be needed is discussion and agreement, to fill the lacunae within the current guidelines. Those involved will want to change to make such an agenda possible.


[Physicians should increase focus on poor medicine adherence among chronically ill patients].
Non-adherence to medicine is common in patients with chronic diseases, contributing to significant worsening of disease, increased mortality and health expenditure. Methods of measuring adherence include self report, prescription refill rates, biomarkers, electronic monitoring and therapeutic outcomes. Yet, no "gold standard" for assessing adherence and no consensus on what is an acceptable level exist. Physicians should be aware of non-adherence and, although it may not always be identical with the evidence-based regimen, they can facilitate good adherence by simplifying regimens and adapting treatments to the patient's lifestyle and preferences.


Recent State of Wearable IMU Sensors Use in People Living with Spasticity: A Systematic Review.
Spasticity is a disabling characteristic of neurological disorders, described by a velocity-dependent increase in muscle tone during passive stretch. During the last few years, many studies have been carried out to assess spasticity using wearable IMU (inertial measurements unit) sensors. This review aims to provide an updated framework of the current research on IMUs wearable sensors in people living with spasticity in recent studies published between 2017 and 2021. A total of 322 articles were screened, then finally 10 articles were selected. Results show the lack of homogenization of study procedures and missing apparatus information in some studies. Still, most studies performed adequately on measures of reporting and found that IMUs wearable data was successful in their respective purposes and goals. As IMUs estimate translational and rotational body motions, we believe there is a strong potential for these applications to estimate velocity-dependent exaggeration of stretch reflexes and spasticity-related characteristics in spasticity. This review also proposes new directions of research that should be challenged by larger study groups and could be of interest to both researchers as well as clinicians. The use of IMUs to evaluate spasticity is a promising avenue to provide an objective measurement as compared to non-instrumented traditional assessments.


Regional Lymphatic Inclusion in Orthotopic Hindlimb Transplantation: Establishment and Assessment of Feasibility in a Rodent Model.
The lymphatic system may play an important role in local immunomodulation in vascularized composite allotransplantation (VCA). Currently, there is no standardized VCA model that includes the regional draining lymphatic tissue. The aim of this study was to develop a rapid and efficient orthotopic hindlimb transplantation model in rats that included the draining lymphatic basin to permit further evaluation of the lymphatic system's role in VCA. Thirty transplantations from Brown Norway rats to Lewis rats were performed. To include the regional lymphatic tissue, the superficial epigastric vessels were preserved to allow retrieval of the corresponding inguinal lymph nodes, including the inguinal fat pad, with the hindlimb. A cuff technique was used for the vein, whereas the conventional microsurgical technique was used for the arterial anastomosis. Vascular patency was confirmed through laser Doppler analysis at postoperative day 1 and histological analysis after euthanasia. The presence and vascularization of the inguinal lymph nodes were verified with indocyanine green lymphoscintigraphy at the time of transplantation. Mean total ischemia time was 69 ± 24 minutes, and mean recipient operation time was 80 ± 19 minutes. Overall transplant survival rate was 93.3%. Laser Doppler analysis showed vascular (technical) success, indocyanine green lymphoscintigraphy confirmed the presence of lymph nodes and the histological analysis revealed patent anastomoses. We successfully developed an experimental orthotopic hindlimb transplantation model in rats that includes the draining inguinal lymphatic basin, which is an important asset in further research on lymphatic tissue and its role in VCA.


Involvement of poly(ADP-ribose) polymerase-1 and XRCC1/DNA ligase III in an alternative route for DNA double-strand breaks rejoining.
The efficient repair of DNA double-strand breaks (DSBs) is critical for the maintenance of genomic integrity. In mammalian cells, the nonhomologous end-joining process that represents the predominant repair pathway relies on the DNA-dependent protein kinase (DNA-PK) and the XRCC4-DNA ligase IV complex. Nonetheless, several in vitro and in vivo results indicate that mammalian cells use more than a single end-joining mechanism. While searching for a DNA-PK-independent end-joining activity, we found that the pretreatment of DNA-PK-proficient and -deficient rodent cells with an inhibitor of the poly(ADP-ribose) polymerase-1 enzyme (PARP-1) led to increased cytotoxicity of the highly efficient DNA double-strand breaking compound calicheamicin gamma1. In addition, the repair kinetics of the DSBs induced by calicheamicin gamma1 was delayed both in PARP-1-proficient cells pretreated with the PARP-1 inhibitor and in PARP-1-deficient cells. In order to get new insights into the mechanism of an alternative route for DSBs repair, we have established a new synapsis and end-joining two-step assay in vitro, operating on DSBs with either nuclear protein extracts or recombinant proteins. We found an end-joining activity independent of the DNA-PK/XRCC4-ligase IV complex but that actually required a novel synapsis activity of PARP-1 and the ligation activity of the XRCC1-DNA ligase III complex, proteins otherwise involved in the base excision repair pathway. Taken together, these results strongly suggest that a PARP-1-dependent DSBs end-joining activity may exist in mammalian cells. We propose that this mechanism could act as an alternative route of DSBs repair that complements the DNA-PK/XRCC4/ligase IV-dependent nonhomologous end-joining.


Expression and regulatory network of long noncoding RNA in rats after spinal cord hemisection injury.
Long noncoding RNAs (lncRNAs) participate in a variety of biological processes and diseases. However, the expression and function of lncRNAs after spinal cord injury has not been extensively analyzed. In this study of right side hemisection of the spinal cord at T10, we detected the expression of lncRNAs in the proximal tissue of T10 lamina at different time points and found 445 lncRNAs and 6522 mRNA were differentially expressed. We divided the differentially expressed lncRNAs into 26 expression trends and analyzed Profile 25 and Profile 2, the two expression trends with the most significant difference. Our results showed that the expression of 68 lncRNAs in Profile 25 rose first and remained high 3 days post-injury. There were 387 mRNAs co-expressed with the 68 lncRNAs in Profile 25. The co-expression network showed that the co-expressed genes were mainly enriched in cell division, inflammatory response, FcγR-mediated cell phagocytosis signaling pathway, cell cycle and apoptosis. The expression of 56 lncRNAs in Profile2 first declined and remained low after 3 days post-injury. There were 387 mRNAs co-expressed with the 56 lncRNAs in Profile 2. The co-expression network showed that the co-expressed genes were mainly enriched in the chemical synaptic transmission process and in the signaling pathway of neuroactive ligand-receptor interaction. The results provided the expression and regulatory network of the main lncRNAs after spinal cord injury and clarified their co-expressed gene enriched biological processes and signaling pathways. These findings provide a new direction for the clinical treatment of spinal cord injury.


Separated after birth.
Bioethics has developed against a backdrop of increased concern for human and civil rights, including the rights of patients to decide about their own treatment. The recent case of Laleh and Ladan Bijani, the twenty-nine-year old Iranian conjoined twins who died in a Singapore hospital on Jul 8, after more than fifty hours of surgery aimed at separating them, highlights the tensions between respect for patient autonomy and professional medical judgment.


Perforation due to ileocaecal salmonellosis.
A 54-year old male patient was admitted with a tentative diagnosis of biliary pancreatitis. After 3 days, he developed an acute abdomen with a pneumoperitoneum. A laparotomy was performed: multiple perforations of the terminal ileum and a necrotic gallbladder were found. A right hemicolectomy with 30 cm of the terminal ileum and a cholecystectomy were carried out. At the same time, positive blood cultures for Salmonella typhi were obtained and this confirmed the diagnosis of ileal perforation due to salmonella typhi infection. This case illustrates that Salmonella typhi infection can be a surgical problem in the western countries.


Carcinoma of the nasal cavity--results of primary and adjuvant radiotherapy.
Carcinomas of the nasal cavity are uncommon and the reported experience with radiotherapy is scarce. From 1969-1984, 62 patients with carcinoma of the nasal cavity received radiotherapy as all or part of initial treatment at the Mallinckrodt Institute of Radiology, Washington University Medical Center. Epidermoid carcinoma was the most common histologic subtype, occurring in 46 cases (73%), undifferentiated carcinoma in 10 cases (16%), and adenoid cystic carcinoma in 6 cases (10%). Minimum follow-up was 2.1 years, maximum 16.9 years, and the median was 6.9 years. Relapse-free survival and overall actuarial survival at 5 years were 47% and 52%, respectively; at 10 years, they were 42% and 32%, respectively. Of 35 recorded deaths, 16 were due to the nasal cavity carcinoma, 17 to intercurrent disease, 2 to postoperative complications. Survival was not significantly affected by histology (epidermoid vs undifferentiated), site, nodal status or treatment (radiotherapy alone vs radiotherapy + surgery). Local control was correlated significantly with tumor extent (p less than 0.04) and marginally with treatment (p = 0.15). Elective neck irradiation was not given. Nodal failure occurred in 10/52 patients (19%) with initially N0 necks. Of four patients presenting with N1 disease, one failed in the untreated contralateral neck.


Serotonin transporter activity and serotonin concentration in platelets of patients with irritable bowel syndrome: effect of gender.
In the past decade, a strong argument has been built for the role of serotonin (5HT) and the serotonin transporter (SERT) in irritable bowel syndrome (IBS). However, it is still not clear how SERT contributes to this clinically heterogeneous disease. The present study addressed this issue by implementing platelet (plt) markers of SERT activity in the assessment protocol. Fasting blood samples of 149 (51 male/98 female) subjects with Rome II and III defined IBS subtypes, and 163 healthy control subjects (CSs; 75 male/88 female) were analyzed for platelet 5HT concentration and 5HT uptake activity [maximum uptake rate (V (max)) and affinity constant (K (m))]. Gender had a significant impact on platelet markers of SERT activity. Male IBS patients showed significantly lower median V (max) and K (m) values than the male CS (V (max) 1.706 vs. 2.148 nmol/10(9) plts x min, P < 0.001; K (m) 346 vs. 410 nmol, P = 0.008) without any significant reduction in platelet 5HT concentration (362 vs. 394 ng/10(9) plts). On the other hand, V (max) values were not different between female IBS patients and female CS (1.642 vs. 1.741 nmol/10(9) plts x min), but platelet 5HT concentration was significantly lower in females with diarrhea-predominant IBS (363 vs. 435 ng/10(9) plts, P < 0.05). Although an absolute extrapolation from platelets to the gastrointestinal tissue does not appear to be justified, our findings demonstrated that the contribution of disturbed SERT activity to IBS is not uniform and is possibly gender-specific. The results suggest that an assessment of SERT function in platelets may help to elucidate the differences between IBS patients in response to drugs affecting the 5HT system.


Relationship of BRCA1 and BRCA2 mutations with cancer burden in the family and tumor incidence.
The aim of the present study is to analyze the relationship of the incidence of mutations in the two major genes BRCA1 and BRCA2 conferring risk of breast cancer (BC) and ovarian cancer (OC) with the cancer burden in families and with the presence and age of onset of BC/OC. We included 704 index patients (IP) and 668 family members of the IP who tested positive for BRCA1/BRCA2 who were studied in the Program of Genetic Counselling in Cancer of the Valencia Community (Spain). We found 129 IPs with deleterious mutations (18.3%), 59 in BRCA1 and 70 in BRCA2, detecting 396 mutations in this kindred. The incidence of mutations and their distribution between BRCA1 and BRCA2 showed a significantly uneven incidence among the family groups (P < 0.001). We found 179 tumors in the 396 mutation carriers (45%) and detected only 11 cancers among the 272 non-mutation carriers (P < 0.001). No differences in the tumor prevalence or the age of onset of cancer between the genes among the mutation carriers were found. The mutation carriers showed a 50% probability of having BC/OC at a median age of 49 years (95% CI 46-52 years) and 78% at the age of 70 years (95% CI: 71-85%). In conclusion the family burden of BC and OC is strongly associated with the incidence of BRCAs mutations and could foretell which of the two BRCAs genes is more likely to have mutations. Mutation carriers have a 50% risk of having BC/OC by the age of 50 years.


Modulation of infection-mediated migration of neutrophils and CXCR2 trafficking by osteopontin.
Osteopontin (OPN) is a pro-inflammatory protein that paradoxically protects against inflammation and bone destruction in a mouse model of endodontic infection. Here we have tested the hypothesis that this effect of OPN is mediated by effects on migration of innate immune cells to the site of infection. Using the air pouch as a model of endodontic infection in mice, we showed that neutrophil accumulation at the site of infection with a mixture of endodontic pathogens is significantly reduced in OPN-deficient mice. Reduced neutrophil accumulation in the absence of OPN was accompanied by an increase in bacterial load. OPN-deficiency did not affect neutrophil survival, CXCR2 ligand expression, or the production of inflammatory cytokines in the air pouch. In vitro, OPN enhanced neutrophil migration to CXCL1, whereas in vivo, inhibition of CXCR2 suppressed cellular infiltration in air pouches of infected wild-type mice by > 50%, but had no effect in OPN-deficient mice. OPN increased cell surface expression of CXCR2 on bone marrow neutrophils in an integrin-αv -dependent manner, and suppressed the internalization of CXCR2 in the absence of ligand. Together, these results support a model where the protective effect of OPN results from enhanced initial neutrophil accumulation at sites of infection resulting in optimal bacterial killing. We describe a novel mechanism for this effect of OPN: integrin-αv -dependent suppression of CXCR2 internalization in neutrophils, which increases the ability of these cells to migrate to sites of infection in response to CXCR2 ligands.


Animal models of chronic inflammatory arthritis.
The use of animals has been indispensable to the investigation of the etiology, pathophysiology, and treatment of juvenile arthritis. Because of ethical concerns about studying children, the difficulty of obtaining tissue, and the heterogeneous manifestations and protean course of chronic arthritis in childhood, the scope of potential research has been severely limited. This brief review summarizes a few of the animal models most commonly used in chronic inflammatory arthritis research: subcutaneous air pouch, antigen-induced (including arthritogenic infectious agent), and spontaneous models. In the spontaneous and antigen-induced animal models of arthritis, local and systemic immunoregulatory abnormalities clearly play a major role in the pathogenesis of arthritis. By elucidating the immune response to those antigens, as well as the role of genetics and environment, the pathogenesis of juvenile rheumatoid arthritis may be better understood. At the present time, however, the complexity of these models precludes more definitive interpretation and extrapolation to human diseases.


FBXO38 mediates PD-1 ubiquitination and regulates anti-tumour immunity of T cells.
Dysfunctional T cells in the tumour microenvironment have abnormally high expression of PD-1 and antibody inhibitors against PD-1 or its ligand (PD-L1) have become commonly used drugs to treat various types of cancer1-4. The clinical success of these inhibitors highlights the need to study the mechanisms by which PD-1 is regulated. Here we report a mechanism of PD-1 degradation and the importance of this mechanism in anti-tumour immunity in preclinical models. We show that surface PD-1 undergoes internalization, subsequent ubiquitination and proteasome degradation in activated T cells. FBXO38 is an E3 ligase of PD-1 that mediates Lys48-linked poly-ubiquitination and subsequent proteasome degradation. Conditional knockout of Fbxo38 in T cells did not affect T cell receptor and CD28 signalling, but led to faster tumour progression in mice owing to higher levels of PD-1 in tumour-infiltrating T cells. Anti-PD-1 therapy normalized the effect of FBXO38 deficiency on tumour growth in mice, which suggests that PD-1 is the primary target of FBXO38 in T cells. In human tumour tissues and a mouse cancer model, transcriptional levels of FBXO38 and Fbxo38, respectively, were downregulated in tumour-infiltrating T cells. However, IL-2 therapy rescued Fbxo38 transcription and therefore downregulated PD-1 levels in PD-1+ T cells in mice. These data indicate that FBXO38 regulates PD-1 expression and highlight an alternative method to block the PD-1 pathway.


Hemicortical allograft reconstruction after resection of low-grade malignant bone tumours.
Low-grade surface tumours of bone may theoretically be treated by hemicortical resection, retaining part of the circumference of the cortex. An inlay allograft may be used to reconstruct the defect. Since 1988 we have performed 22 hemicortical procedures in selected patients with low-grade parosteal osteosarcoma (6), peripheral chondrosarcoma (6) and adamantinoma (10). Restricted medullary involvement was not a contraindication for this procedure. There was no evidence of local recurrence or distant metastasis at a mean follow-up of 64 months (27 to 135). Wide resection margins were obtained in 19 patients. All allografts incorporated completely and there were no fractures or infections. Fractures of the remaining hemicortex occurred in six patients and were managed successfully by casts or by osteosynthesis. The functional results were excellent or good in all except one patient. Hemicortical procedures for selected cases of low-grade surface tumours give excellent oncological and functional outcomes. There was complete remodelling and fewer complications when compared with larger intercalary procedures. The surgery is technically demanding but gives good clinical results.


A new polymorph of succinylcholinium diiodide: comparison of succinylcholinium structures.
The title compound {systematic name: trimethyl[2-({4-oxo-4-[2-(trimethylazaniumyl)ethoxy]butanoyl}oxy)ethyl]azanium diiodide}, C(14)H(30)N(2)O(4)(2+)·2I(-), is a salt of the succinylcholinium cation. There is one formula unit in the asymmetric unit, represented by two anions and two halves of two cations which lie on centres of inversion. The component species are stabilized by electrostatic interactions, and C-H···I and C-H···O hydrogen bonds are also present.


The effect of limited aeration on swine manure phosphorus removal.
Two low level aeration schemes (intermittent vs. continuous) were investigated on a laboratory scale, in conjunction with swine manure pH adjustment using sodium hydroxide (1.0 M), for manure phosphorus (P) removal. According to the data, an 80% reduction in soluble P was observed when the manure pH was increased to 8. Both intermittent and continuous aeration treatments could raise manure pH above 8 with an airflow rate of 1 L/minute in a period of 15 days. A drastic increase in pH (about 1 unit) was observed for both aeration schemes within the first day of test, resulting in a 76% reduction in soluble P concentration in the liquid. It appeared that there is no difference in terms of P removal between the two aeration programs, suggesting that the intermittent aeration be preferred to save energy while still achieving the same level of P removal.


Dose and Timing of Prenatal Alcohol Exposure and Maternal Nutritional Supplements: Developmental Effects on 6-Month-Old Infants.
Fetal alcohol spectrum disorders are more common in disadvantaged populations. Environmental factors, like suboptimal nutrition, may potentiate the developmental effects of prenatal alcohol exposure. To evaluate the impact of micronutrients, including choline, on reduction of effects of exposure, we examined timing and dose of alcohol and effects of nutritional supplementation at two OMNI-Net sites in Western Ukraine that included high and low risk individuals. Alcohol-using and nondrinking women were randomized to one of three multivitamin/mineral supplement groups: none, multivitamins/minerals (MVM), and multivitamin/minerals plus choline. Children (N = 367) were tested at 6 months with the Bayley Scales of Infant Development (2nd ED) yielding standard scores for Mental Development Index (MDI), Psychomotor Development Index (PDI) and Behavior. Generalized linear modeling was used: (1) for factorial analysis of effects of alcohol group, multivitamin/minerals, and choline supplementation; and (2) to examine the relationship between amount and timing of alcohol (ounces of absolute alcohol/day [ozAA/day] peri-conception and on average in the second trimester) and MVM supplementation on developmental outcomes while controlling sex, social class, and smoking. MDI was significantly impacted by peri-conceptual alcohol dose (X2(1), p < .001) with more alcohol associated with lower scores and males more negatively affected than females (X2(1), p < .002). Micronutrient supplementation had a protective effect; those receiving supplements performed better ([Formula: see text], p < .005). The PDI motor scores did not differ by group but were affected by peri-conceptual alcohol dose (X2(1), p < .04). Multivitamin/mineral supplementation can reduce the negative impact of alcohol use during pregnancy on specific developmental outcomes.


[Culture and psychiatry: connections or contributions?].
Fifteen years ago, Pelicier wrote the "what distinguishes contemporary ethnology from the most honest studies of the past, is that it does not attempt to demonstrate anything but rather to respect the topic of study and that it shuns stereotypes and interpretations". Connection or contribution? Who contributes what to whom and who connects what to whom? We propose a reflection on the relationship between two subjects of different culture and the contribution that one could make by connecting to the other. Exposition and/or statement. The only means that we have is our memory and what others have given us to hear, for lack of ability to listen.


Role of DREF in transcriptional regulation of the Drosophila p53 gene.
The tumor suppressor protein p53 has a critical role in safeguarding the integrity of the genome. Its functions are well understood but factors responsible for the transcriptional regulation of the p53 gene are almost entirely unknown. The DNA replication-related element (DRE)/DNA replication-related element-binding factor (DREF) transcriptional regulatory system is established as a master key to cell proliferation in Drosophila. DREF binds specifically to DRE sequences in the Drosophila p53 (dmp53) gene promoter as shown using anti-DREF antibodies in chromatin immunoprecipitation assays. Furthermore, a rough eye phenotype because of overexpression of DREF in Drosophila eye imaginal disks could be suppressed by half dose reduction of the dmp53 gene. In addition, the level of mRNA of dmp53 was decreased in DREF-knockdown cells and transient expression of the luciferase gene under control of the wild-type dmp53 gene promoter showed strong promoter activity in S2 cells, but this was almost completely abrogated with a DRE-mutated promoter. Requirement of DREs for dmp53 promoter activity was further confirmed by anti-beta-galactosidase antibody-staining of various tissues from transgenic flies carrying dmp53 promoter-lacZ fusion genes. These results indicate that DREF is necessary for dmp53 gene promoter activity.


Sumatriptan nasal spray for the acute treatment of migraine. Results of two clinical studies.
Sumatriptan nasal spray may be particularly useful for patients whose nausea and vomiting preclude them from using oral migraine medication or for patients who prefer not to use an injectable migraine medication. The objective of this study was to evaluate in two clinical studies the efficacy and tolerability of the intranasal form of sumatriptan in the acute treatment of a single migraine attack. International Headache Society-diagnosed adult migraineurs in two randomized, double-blind, parallel-group, multicenter studies (n = 409 and 436) used sumatriptan nasal spray 20 mg, 10 mg, or placebo (2:1:1) for the acute treatment of a single migraine attack at home. Predose and at predetermined postdose intervals, patients recorded headache severity (none, mild, moderate, severe); time to meaningful relief; clinical disability (none, mildly impaired, severely impaired, bed rest required); presence/absence of nausea, photophobia, and phonophobia; and the occurrence of adverse events. Two hours postdose in the two studies, moderate or severe baseline pain was reduced to mild or none in 62 to 63% of patients treated with sumatriptan 20 mg, 43 to 54% of patients treated with sumatriptan 10 mg, and 29 to 35% of placebo-treated patients (p < 0.05 20 mg versus placebo for both studies and 10 mg versus placebo for study 1). Onset of relief relative to placebo began as early as 15 minutes postdose (sumatriptan 20 mg, study 2). Clinical disability at 2 hours postdose was reported as mildly impaired or normal in 72 to 74% of patients treated with sumatriptan 20 mg, 56 to 68% of patients treated with sumatriptan 10 mg, and 47 to 58% of placebo-treated patients (p < 0.05 20 mg versus placebo for both studies). Similar efficacy rates were observed for nausea, photophobia, and phonophobia. The most common adverse event in the active treatment groups was disturbance of taste (bad, bitter, or unpleasant taste). Aside from this event, the pattern and incidence of adverse events did not differ among treatment groups. From these results we determined that sumatriptan nasal spray is a rapidly effective, well-tolerated migraine treatment. The 20-mg dose was effective in treating the entire migraine symptom complex, and the 10-mg dose was less consistently effective.


[Hip fracture in the elderly: epidemiology and costs of care].
The aim of this study was to describe the epidemiology and to estimate the direct medical costs of hip fracture among elderly patients in Mexico. An observational, cross sectional and retrospective study was undertaken. Hospital discharge and surgical procedures for the period 2013-2018 were the databases used for the analysis, and obtained from General Directorate of Health Information. Variables included were sex, federal entity, age, year of discharge, and fracture type according to the CIE-10; and also, the supplies needed for the surgical procedures. A total of 16,829 patients with hip fracture were discharge, 69% were women, and the mean for age was 79 years old and for the hospital stay length was nine days. The most frequent fracture type was the femur neck with 77% and the average medical costs was USD$45,122,228.00. Falling risks increase with age, especially in patients among 80-89 years of age, hence, is expected that this type of pathology increases in the following years. The medical costs for treatment of hip fracture represents an economic impact on health services. For that reason, the implementation of prevention strategies, risk of falling for example, is the one of most efficient approach.


Determination of phthalates in fruit jellies by dispersive SPE coupled with HPLC-MS.
In this study, a simple, rapid and sensitive method for the determination of five phthalates including dimethyl phthalate, diethyl phthalate, dipropyl phthalate, benzyl butyl phthalate, and dicyclohexyl phthalate in fruit jellies by LC coupled with MS has been developed. Samples were pretreated by a dispersive SPE method, termed QuEChERS, which is an acronym for quick, easy, cheap, effective, rugged, and safe. The standard calibration curves were linear for all the analytes over the concentration range of 10-250 ng/mL, and the correlation coefficients ranged from 0.9976 to 0.9991. The LODs and LOQs were in the ranges of 0.09-3.68 ng/mL and 0.28-11.25 ng/mL, respectively. The accuracy of this method was evaluated by measuring the recovery from spiked samples. The recoveries of all five phthalates from samples spiked at three different concentrations (0.01, 0.03, and 0.05 mg/kg), were in the ranges of 83.5-103.9%, 86.7-95.8%, and 87.1-95.2%, respectively. The RSD values for the samples spiked at 0.01, 0.03, and 0.05 mg/kg ranged from 2.0-7.6%, 1.4-6.4%, and 1.2-3.8%, respectively. The method has been used for the analysis of real samples and BBP and DEP were found in real samples.


Stability of the parametrically excited damped inverted pendulum: theory and experiment.
The parametrically driven, damped, inverted pendulum can be dynamically stabilized in particular regions of the parameter space. The impact of damping on dynamic stabilization can be stabilizing or destabilizing depending on the location in parameter space (i.e., drive frequency and amplitude). Floquet analysis and numerical simulations were used to determine the stable regions. An experiment was conducted that verifies the model. Physical explanations and simple bounding approximations are provided to summarize findings. The utility of the highly damped pendulum results are illustrated by drawing the analogy to dynamic stabilization of the Rayleigh-Taylor instability: it permits ready demonstration that dynamic stabilization is impossible in that system absent surface tension.


Narrative review of contemporary treatment options in the care of patients with obstructive sleep apnoea.
Snoring and obstructive sleep apnoea (OSA) are increasingly common conditions, and confer a significant health and socioeconomic burden. Furthermore, untreated OSA represents a significant mortality risk. Patients require careful assessment, including detailed clinical history and examination, sleep study and drug-induced sleep endoscopy (DISE). Although nasal continuous positive airway pressure (nCPAP) is the gold standard treatment for moderate and severe OSA, multidisciplinary team assessment is often required to develop the best treatment plan for an individual, especially when nasal CPAP is poorly tolerated. There is a wide range of medical and surgical treatment options, and following appropriate patient selection and assessment, a focused site-specific, often multilevel, intervention is indicated. There is an increasing body of evidence in the literature supporting these multilevel interventions and with agreement on standardized outcome measures more trials are likely to improve the robustness of these data further.


The neurobiology of cognitive control in successful cocaine abstinence.
Extensive evidence demonstrates that current cocaine abusers show hypoactivity in anterior cingulate and dorsolateral prefrontal cortex and respond poorly relative to drug-naïve controls on tests of executive function. Relatively little is known about the cognitive sequelae of long-term abstinence in cocaine addicts. Here, we use a GO-NOGO task in which successful performance necessitated withholding a prepotent response to assay cognitive control in short- and long-term abstinent cocaine users (1-5 weeks and 40-102 weeks, respectively). We report significantly greater activity in prefrontal, cingulate, cerebellar and inferior frontal gyrii in abstinent cocaine users for both successful response inhibitions and errors of commission. Moreover, this relative hyperactivity was present in both abstinent groups, which, in the presence of comparable behavioral performance, suggests a functional compensation. Differences between the short- and long-abstinence groups in the patterns of functional recruitment suggest different cognitive control demands at different stages in abstinence. Short-term abstinence showed increased inhibition-related dorsolateral and inferior frontal activity indicative of the need for increased inhibitory control while long-term abstinence showed increased error-related ACC activity indicative of heightened behavioral monitoring. The results suggest that the integrity of prefrontal systems that underlie cognitive control functions may be an important characteristic of successful long-term abstinence.


Authorization & security aspects in the middleware-based healthcare information system.
The integration and evolution of existing systems represents one of the most urgent priorities of health care information systems in order to allow the whole organisation to meet the increasing clinical organisational and managerial needs. The CEN ENV 12967-1 'Healthcare Information Systems Architecture'(HISA) standard defines an architectural approach based on a middleware of business-specific common services, enabling all parts of the local and geographical system to operate on the common information heritage of the organisation and on exploiting a set of common business-oriented functionality. After an overview on the key aspects of HISA, this paper discusses the positioning of the authorization and security aspects in the overall architecture. A global security framework is finally proposed.


Surface-bulk coupling in a Bi2Te3 nanoplate grown by van der Waals epitaxy.
We report an experimental study of the effect of coherent surface-bulk electron scattering on quantum transport in a three-dimensional topological insulator Bi2Te3 nanoplate. The nanoplate is grown via van der Waals epitaxy on a mica substrate and a top-gated Hall-bar device is fabricated from the nanoplate directly on the growth substrate. Top-gate voltage dependent measurements of the sheet resistance of the device reveal that the transport carriers in the nanoplate are of n-type and that, with decreasing top gate voltage, the carrier density in the nanoplate is decreased. However, the mobility is increased with decreasing top-gate voltage. This mobility increase with decreasing carrier density in the nanoplate is demonstrated to arise from a decrease in bulk-to-surface electron scattering rate. Low-field magnetotransport measurements are performed at low temperatures. The measured magnetoconductivity of the nanoplate shows typical weak anti-localization (WAL) characteristics. We analyze the measurements by taking surface-bulk inter-channel electron scattering into account and extract dephasing times τφ, diffusion coefficients D of electrons at the top surface and in the bulk, and the surface-bulk scattering times τSB as a function of top-gate voltage and temperature. It is found that the dephasing in the nanoplate arises dominantly from electron-electron scattering with small energy transfers. It is also found that the ratio of τφ/τSB (a measure of the surface-bulk electron coherent coupling) is decreased with decreasing gate voltage or increasing temperature. We demonstrate that taking the surface-bulk coherent electron scattering in our Bi2Te3 nanoplate into account is essential to understand quantum transport measurements at low temperatures.


Effects of calcium antagonists on release of [3H]noradrenaline in rabbit aorta.
The effects of several organic Ca antagonists and putative calmodulin antagonists on the release of [3H]noradrenaline from rabbit aorta were examined. A 65.4 mM K solution and electrical stimulation induced a Ca-dependent increase in the 3H-efflux from the adventitial layer (containing nerve terminals) but not from the media-intimal layer. Verapamil, D600, N-(6-aminohexyl)-5-chloro-l-naphthalenesulphonamide (W-7) and N2-dansyl-L-arginine-4-t-butylpiperidine amide (TI 233), in the concentration of 10(-5) M, did not inhibit the increase in 3H-efflux. A high concentration (2 X 10(-4) M) of verapamil induced a Ca-independent increase in the 3H-efflux from the adventitia but not from the media-intimal layer. D600, diltiazem, W-7 and TI233, in the concentration of 2 X 10(-4) M, also increased the 3H-efflux; 65.4 mM K, added in the presence of 2 X 10(-4) M verapamil or W-7, produced no further increase in 3H-efflux. The 3H-efflux evoked by electrical stimulation was only partially inhibited by 2 X 10(-4) M verapamil. It is suggested that the evoked release of noradrenaline in rabbit aorta is relatively insensitive to organic Ca antagonists and calmodulin antagonists, and that high concentrations of these inhibitors themselves release noradrenaline by a mechanism independent of external Ca.


Evaluation of a screening system for obesogenic compounds: screening of endocrine disrupting compounds and evaluation of the PPAR dependency of the effect.
Recently the environmental obesogen hypothesis has been formulated, proposing a role for endocrine disrupting compounds (EDCs) in the development of obesity. To evaluate this hypothesis, a screening system for obesogenic compounds is urgently needed. In this study, we suggest a standardised protocol for obesogen screening based on the 3T3-L1 cell line, a well-characterised adipogenesis model, and direct fluorescent measurement using Nile red lipid staining technique. In a first phase, we characterised the assay using the acknowledged obesogens rosiglitazone and tributyltin. Based on the obtained dose-response curves for these model compounds, a lipid accumulation threshold value was calculated to ensure the biological relevance and reliability of statistically significant effects. This threshold based method was combined with the well described strictly standardized mean difference (SSMD) method for classification of non-, weak- or strong obesogenic compounds. In the next step, a range of EDCs, used in personal and household care products (parabens, musks, phthalates and alkylphenol compounds), were tested to further evaluate the obesogenicity screening assay for its discriminative power and sensitivity. Additionally, the peroxisome proliferator activated receptor γ (PPARγ) dependency of the positive compounds was evaluated using PPARγ activation and antagonist experiments. Our results showed the adipogenic potential of all tested parabens, several musks and phthalate compounds and bisphenol A (BPA). PPARγ activation was associated with adipogenesis for parabens, phthalates and BPA, however not required for obesogenic effects induced by Tonalide, indicating the role of other obesogenic mechanisms for this compound.


'Candidatus Lumbricincola', a novel lineage of uncultured Mollicutes from earthworms of family Lumbricidae.
Molecular signatures of new, as yet uncultured mollicute-like organisms (MLOs) have been detected in total rRNA and DNA extracted from tissues, gut contents and casts of four species of the earthworm family Lumbricidae. The MLO 16S rRNA sequences exhibited low identity to those of known Mollicutes species and formed a monophyletic cluster distantly affiliated to the 'Candidatus Bacilloplasma' (84.9%) and almost equidistant to the other main phylogenetic group of Mollicutes (< 79.8%) and the classes Bacilli (< 79.5%) and Clostridia (< 76.1%). SSCP profiling and sequence analysis of bands and bacterial clones derived from the earthworms and substrata revealed high phylogenetic relatedness of MLOs in earthworms from different geographic locations (Russia and Germany), with no obvious host species specificity being observed. Fluorescence in situ hybridization (FISH) analysis with a nucleotide probe specific for the new MLO group localized them to the coelomic fluids of earthworms. A new taxonomic group within the Mollicutes, designated 'Candidatus Lumbricincola', is proposed to include these as yet uncultured organisms.


Terrimonas rubra sp. nov., isolated from a polluted farmland soil and emended description of the genus Terrimonas.
A salmon-red-pigmented bacterial strain, designated M-8(T), was isolated from a polluted farmland soil sample in China and was characterized in a taxonomic study using a polyphasic approach. Strain M-8(T) was Gram-stain-negative, rod-shaped, non-motile and non-spore-forming. Growth occurred at 20-37 °C, at pH 5.0-10.0 and with 0-2% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain M-8(T) belonged to the genus Terrimonas.16S rRNA gene sequence similarity values between strain M-8(T) and the type strains of the three recognized species of the genus Terrimonas, Terrimonas ferruginea KACC 11310(T), Terrimonas aquatica LMG 24825(T) and Terrimonas lutea KACC 13047(T), were 97.1, 96.3 and 95.3%, respectively. The predominant respiratory quinone was menaquinone-7 (MK-7) and the major fatty acids were iso-C(15:0), iso-C(17:0) 3-OH and summed feature 3 (comprising C(16:1)ω7c and/or C(16:1)ω6c). The DNA G+C content of strain M-8(T) was 47.0 mol%. On the basis of genotypic and phenotypic data, strain M-8(T) is considered to represent a novel species of the genus Terrimonas, for which the name Terrimonas rubra sp. nov. is proposed. The type strain is M-8(T) (=CCTCC AB 2010401(T)=KCTC 23299(T)). An emended description of the genus Terrimonas is also presented.


Increased cytochrome c correlates with poor survival in aggressive lymphoma.
Mitochondria are central to a variety of cellular processes, from metabolism to cell death. In this study, we demonstrated that an increase in the critical mitochondrial protein, cytochrome c, correlated with drug resistance in a cell culture model of aggressive lymphoma. Increased cytochrome c expression was also correlated with decreased survival in the aggressive diffuse large B-cell and mantle cell lymphomas, but not in the indolent follicular lymphoma. This suggests that an increased reliance on the mitochondria for energy allows tumor cells to be metabolic opportunists and contribute to tumor development and drug resistance.


Molecular pathology of human prion diseases.
Prion diseases are fatal neurodegenerative conditions in humans and animals. In this review, we summarize the molecular background of phenotypic variability, relation of prion protein (PrP) to other proteins associated with neurodegenerative diseases, and pathogenesis of neuronal vulnerability. PrP exists in different forms that may be present in both diseased and non-diseased brain, however, abundant disease-associated PrP together with tissue pathology characterizes prion diseases and associates with transmissibility. Prion diseases have different etiological background with distinct pathogenesis and phenotype. Mutations of the prion protein gene are associated with genetic forms. The codon 129 polymorphism in combination with the Western blot pattern of PrP after proteinase K digestion serves as a basis for molecular subtyping of sporadic Creutzfeldt-Jakob disease. Tissue damage may result from several parallel, interacting or subsequent pathways that involve cellular systems associated with synapses, protein processing, oxidative stress, autophagy, and apoptosis.