Augmentation of skin test reactivity and lymphocyte blastogenesis in patients with AIDS treated with transfer factor.
Nine patients with the acquired immunodeficiency syndrome (AIDS) were administered four doses of pooled transfer factor obtained from the lymphocytes of three healthy controls and three homosexuals with stable lymphadenopathy and serum antibody to the human immunodeficiency virus. Before receiving transfer factor, all patients exhibited anergy to skin test antigens. After four weeks of transfer factor therapy, six of seven patients tested had at least one skin test response. Lymphocyte blastogenic responses to phytohemagglutinin rose from a stimulation index of 6.77 +/- 1.31 before treatment to 19.77 +/- 6.24 after four weeks of transfer factor therapy. Smaller but significant increases were also seen in blastogenic responses to antigens. Improvements in immune responses diminished after administration of transfer factor was halted. Thus, administration of transfer factor to patients with AIDS resulted in partial immune reconstitution. Further studies are indicated to examine the clinical efficacy of this immune response modifier in the treatment of AIDS.


Expression of common acute lymphoblastic leukemia-associated antigen on germ cell tumor.
A mediastinal germ cell tumor is described that reacts with the anti-common acute lymphoblastic leukemia-associated antigen antibody J5 using both immunofluorescence and immunoperoxidase techniques. This antigen has been reported recently on various cell lines including melanoma, colon, and breast. It has also been seen on normal fibroblasts and peripheral granulocytes. This is believed to be the first description of a solid nonlymphoid neoplasm possessing this antigen, and the implications regarding prognosis and therapy are discussed.


Cross-validation of the Turkish version of the 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ 25).
To test the validity and reliability of the Turkish version of the self-administered form of the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ 25). Patients with no limitations to respond to a health status interview and affected by a chronic eye disease were enrolled. The Turkish versions of the abbreviated form of World Health Organization Quality of Life (WHOQOL-BREF) and the NEI-VFQ 25 instruments were administered to all participants. The mean (SD) age of the participants was 60.9 (14.5) years. There were 61 patients with one of the following conditions: Cataract (57.4%), diabetic retinopathy (13.2%), age related macular degeneration (ARMD) (11.4%), glaucoma (9.8%) and degenerative myopia (8.2%). The Cronbach alpha of the overall scale was 0.97; the Cronbach alpha ranged from 0.94 to 0.78 for the subscales. The physical, psychological, environmental and social domains of the WHOQOL-BREF had fair to good correlations with the NEI-VFQ 25 (r = 0.68 to r = 0.26), which indicated a sufficient convergent validity. Patients with lower visual acuity (VA) had lower index scores than those with higher VA (p = 0.001), which showed a sufficient responsiveness. Statistical analysis showed that Turkish version of the NEI-VFQ is a valid and reliable instrument to measure vision-related quality of life in patients with chronic eye diseases.


Preliminary experience with laparoscopic Foley's YV plasty for ureteropelvic junction obstruction in children.
Laparoscopic dismembered pyeloplasty is an acceptable option for ureteropelvic junction (UPJ) obstruction in the paediatric population. We compared our results of laparoscopic dismembered and non-dismembered Foley's YV pyeloplasty. Children presenting with hydronephrosis secondary to UPJ obstruction formed the study group. Foley's YV plasty was planned whenever it was observed that a tension free dismembered pyeloplasty was not possible in spite of all possible manoeuvres. Children were followed up for urinary infection, and renogram was repeated after 3 months. During the study period, 108 children (63 male and 45 female) with a mean age of 4.94 ± 2.78 years underwent laparoscopic dismembered pyeloplasty and the remaining 11 children (5 male and 6 female) with a mean age of 4.00 ± 1.776 years underwent laparoscopic Foley's YV plasty. There were no major peri-operative complications noted and conversion to open was not necessary in any child. Renogram done at 3 months post-operatively showed good drainage and improvement of renal function. Laparoscopic Foley's YV pyeloplasty is a safe and effective technique in appropriately selected cases of primary UPJ obstruction in children.


Alteration of disc formation in photoreceptors of rat retina.
Autoradiographic experiments demonstrate that the renewal process of the rod photoreceptors in the rat retina is altered during essential fatty acid deficiency. After the administration of tritiated amino acids, animals raised on a fat-free ration show no evidence of disc formation, while those raised on a normnal ration show disc formation and renewal. The latter process is apparently dependent upon the availability of linoleic or linolenic (or both) fatty acids.


2D/3D fetal cardiac dataset segmentation using a deformable model.
To segment the fetal heart in order to facilitate the 3D assessment of the cardiac function and structure. Ultrasound acquisition typically results in drop-out artifacts of the chamber walls. The authors outline a level set deformable model to automatically delineate the small fetal cardiac chambers. The level set is penalized from growing into an adjacent cardiac compartment using a novel collision detection term. The region based model allows simultaneous segmentation of all four cardiac chambers from a user defined seed point placed in each chamber. The segmented boundaries are automatically penalized from intersecting at walls with signal dropout. Root mean square errors of the perpendicular distances between the algorithm's delineation and manual tracings are within 2 mm which is less than 10% of the length of a typical fetal heart. The ejection fractions were determined from the 3D datasets. We validate the algorithm using a physical phantom and obtain volumes that are comparable to those from physically determined means. The algorithm segments volumes with an error of within 13% as determined using a physical phantom. Our original work in fetal cardiac segmentation compares automatic and manual tracings to a physical phantom and also measures inter observer variation.


An ethnic predilection for fetal echogenic intracardiac focus identified during targeted midtrimester ultrasound examination: A retrospective review.
BACKGROUND: Echogenic intracardiac focus (EIF) has been identified as a common ultrasound finding in association with fetal aneuploidy. Little is known about the association of this soft marker aneuploidy in various ethnic groups. Although it is commonly thought Asians in general have a higher incidence of EIF, it is unknown whether this also applies to Japanese as a subpopulation. The purpose of this study is to determine the antenatal incidence and postnatal significance of EIF observed during sonography in Japanese patients. METHODS: A cohort of Japanese patients who underwent ultrasound screening from 1997 to 1999 in the ultrasound unit at the New York University School of Medicine was identified. Variables included age, gestational age, serum markers, and the presence or absence of aneuploidy. Patients with first degree paternal or maternal Japanese ancestry were included for analysis. Examinations were performed between 14 and 24 weeks gestation. The prevalence of EIF was calculated. The control group was based on previously published data in the U.S (7.3% prevalence). RESULTS: A total of 154 subjects were identified, 148 were available for final analysis. Twenty-two fetuses had an EIF, 19 (86.4%) left-sided, 3 (13.6%) right-sided. Seventeen patients had other sonographic markers associated with aneuploidy. The mean maternal age at diagnosis was 30.7 +/- 3.9 years and the mean gestational age was 19.8 +/- 1.6 weeks. The prevalence of EIF was 14.8%. Compared to published population prevalence, there was a statistically significant difference (p < 0.005). No abnormal karyotypes were found. CONCLUSION: Asians of Japanese origin may have a higher prevalence of echogenic intracardiac foci, thus affecting the positive predictive value of this sonographic marker for aneuploidy.


[Computer program for processing lung scintigrams].
The paper is concerned with an algorithm of a program for pulmonoscintigram processing. The program developed in the algorithmic languages Basic and Assembler on the basis of this algorithm, made it possible to facilitate the data processing, to lower a physician's competence as a computer operator, to raise the objectivity of diagnosis of pulmonary diseases, etc. The program is intended for computers Vip-450, Vip-550 and MCS-560, Technicare, USA.


Roflumilast: first phosphodiesterase 4 inhibitor approved for treatment of COPD.
In April 2010, the European Medicines Agency Committee for Medicinal Products for Human Use recommended approval of roflumilast, a selective phosphodiesterase 4 inhibitor, for the "maintenance treatment of severe chronic obstructive pulmonary disease (COPD, FEV(1) postbronchodilator less than 50% predicted) associated with chronic bronchitis in adult patients with a history of frequent exacerbations as add-on to bronchodilator treatment". This decision was based, in part, on the results of several large, international, multicenter, randomized, placebo-controlled trials of either six or 12 months' duration that had been undertaken in COPD patients. Roflumilast 500 mug daily improved lung function and reduced exacerbations in patients with more severe COPD, especially those with chronic bronchitis, frequent exacerbations, or who required frequent rescue inhaler therapy in the placebo-controlled trials. It also improved lung function and reduced exacerbations in patients with moderately severe COPD treated with salmeterol or tiotropium. Advantages of roflumilast over inhaler therapy are that it is an oral tablet and only needs to be taken once daily. While taking roflumilast, the most common adverse effects patients experienced were gastrointestinal upset and headache. Weight loss, averaging 2.2 kg, occurred in patients treated with roflumilast. Patients taking roflumilast were more likely to drop out of the trials than patients in the control groups. Patients who discontinued therapy usually did so during the first few weeks and were more likely to have experienced gastrointestinal side effects. Roflumilast is the first selective phosphodiesterase 4 inhibitor and will offer physicians another treatment option for patients with more severe COPD.


Does the Degree of Trunk Bending Predict Patient Disability, Motor Impairment, Falls, and Back Pain in Parkinson's Disease?
Background: Postural abnormalities in Parkinson's disease (PD) form a spectrum of functional trunk misalignment, ranging from a "typical" parkinsonian stooped posture to progressively greater degrees of spine deviation. Objective: To analyze the association between degree of postural abnormalities and disability and to determine cut-off values of trunk bending associated with limitations in activities of daily living (ADLs), motor impairment, falls, and back pain. Methods: The study population was 283 PD patients with ≥5° of forward trunk bending (FTB), lateral trunk bending (LTB) or forward neck bending (FNB). The degrees were calculated using a wall goniometer (WG) and software-based measurements (SBM). Logistic regression models were used to identify the degree of bending associated with moderate/severe limitation in ADLs (Movement Disorders Society Unified PD Rating Scale [MDS-UPDRS] part II ≥17), moderate/severe motor impairment (MDS-UPDRS part III ≥33), history of falls (≥1), and moderate/severe back pain intensity (numeric rating scale ≥4). The optimal cut-off was identified using receiver operating characteristic (ROC) curves. Results: We found significant associations between modified Hoehn & Yahr stage, disease duration, sex, and limitation in ADLs, motor impairment, back pain intensity, and history of falls. Degree of trunk bending was associated only with motor impairment in LTB (odds ratio [OR] 1.12; 95% confidence interval [CI], 1.03-1.22). ROC curves showed that patients with LTB of 10.5° (SBM, AUC 0.626) may have moderate/severe motor impairment. Conclusions: The severity of trunk misalignment does not fully explain limitation in ADLs, motor impairment, falls, and back pain. Multiple factors possibly related to an aggressive PD phenotype may account for disability in PD patients with FTB, LTB, and FNB.


Blood Pressure and Cognitive Decline Over 8 Years in Middle-Aged and Older Black and White Americans.
Although the association between high blood pressure (BP), particularly in midlife, and late-life dementia is known, less is known about variations by race and sex. In a prospective national study of 22 164 blacks and whites ≥45 years without baseline cognitive impairment or stroke from the REGARDS cohort study (Reasons for Geographic and Racial Differences in Stroke), enrolled 2003 to 2007 and followed through September 2015, we measured changes in cognition associated with baseline systolic and diastolic BP (SBP and DBP), as well as pulse pressure (PP) and mean arterial pressure, and we tested whether age, race, and sex modified the effects. Outcomes were global cognition (Six-Item Screener; primary outcome), new learning (Word List Learning), verbal memory (Word List Delayed Recall), and executive function (Animal Fluency Test). Median follow-up was 8.1 years. Significantly faster declines in global cognition were associated with higher SBP, lower DBP, and higher PP with increasing age ( P<0.001 for age×SBP×follow-up-time, age×DBP×follow-up-time, and age×PP×follow-up-time interaction). Declines in global cognition were not associated with mean arterial pressure after adjusting for PP. Blacks, compared with whites, had faster declines in global cognition associated with SBP ( P=0.02) and mean arterial pressure ( P=0.04). Men, compared with women, had faster declines in new learning associated with SBP ( P=0.04). BP was not associated with decline of verbal memory and executive function, after controlling for the effect of age on cognitive trajectories. Significantly faster declines in global cognition over 8 years were associated with higher SBP, lower DBP, and higher PP with increasing age. SBP-related cognitive declines were greater in blacks and men.


Giant cell tumor of the thoracic spine simulating mediastinal neoplasm.
A case of giant cell tumor of the thoracic spine simulating mediastinal neoplasm was identified on plain films, CT scans, MR images, and with scintigraphy. CT showed a hypervascular soft-tissue mass with shell-like calcification in the right upper mediastinum. MR imaging showed a collapse of the T1 vertebral body and a mass extending to the mediastinum. The mass had a low signal on T1-weighted MR images and a predominantly high signal on T2-weighted images with heterogeneity. Technetium-99m methylene diphosphonate bone scintigraphy showed intense uptake in both the T1 and marginal parts of the mediastinal mass. There was no accumulation of gallium-67 citrate, but 18-fluorine fluorodeoxyglucose positron emission tomography showed marked uptake. The variation in these imaging findings played an important role in the differential diagnosis of this uncommon mediastinal mass.


Roles of Phonation Types and Decoders' Gender in Recognizing Mandarin Emotional Speech.
Capturing phonation types such as breathy, modal, and pressed voices precisely can facilitate the recognition of human emotions. However, little is known about how exactly phonation types and decoders' gender influence the perception of emotional speech. Based on the modified Brunswikian lens model, this article aims to examine the roles of phonation types and decoders' gender in Mandarin emotional speech recognition by virtue of articulatory speech synthesis. Fifty-five participants (28 male and 27 female) completed a recognition task of Mandarin emotional speech, with 200 stimuli representing five emotional categories (happiness, anger, fear, sadness, and neutrality) and five types (original, copied, breathy, modal, and pressed). Repeated-measures analyses of variance were performed to analyze recognition accuracy and confusion data. For male and female decoders, the recognition accuracy of anger from pressed stimuli and fear from breathy stimuli was high; across all phonation-type stimuli, the recognition accuracy of sadness was also high, but that of happiness was low. The confusion data revealed that in recognizing fear from all phonation-type stimuli, female decoders chose fear responses more frequently and neutral responses less frequently than male decoders. In recognizing neutrality from breathy stimuli, female decoders significantly reduced their choice of neutral responses and misidentified neutrality as anger, while male decoders mistook neutrality from pressed stimuli for anger. This study revealed that, in Mandarin, phonation types play crucial roles in recognizing anger, fear, and neutrality, while the recognition of sadness and happiness seems not to depend heavily on phonation types. Moreover, the decoders' gender affects their recognition of neutrality and fear. These findings support the modified Brunswikian lens model and have significance for diagnosis and intervention among clinical populations with hearing impairment or gender-related psychiatric disorders. https://doi.org/10.23641/asha.24302221.


The effects of long-term exposure to a 2450 MHz electromagnetic field on growth and pubertal development in female Wistar rats.
The aim of this study was to investigate the effects of a 2450 MHz electromagnetic field (EMF) (wireless internet frequency) on the growth and development of female Wistar rats. The study was conducted on three groups of rats. The prenatal and postnatal groups were exposed to EMF 1 h/day beginning from intrauterine and postnatal periods, respectively. The third group was the sham-exposed group. Growth, nutrition and vaginal opening (VO) were regularly monitored. Serum and tissue specimens were collected at puberty. Histological examinations, total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) measurements in ovary and brain tissues and also immunohistochemical staining of the hypothalamus were performed besides the determination of serum FSH, LH, E2 and IGF-1 values. Birth masses of the groups were similar (p > 0.05). Mass gain per day was significantly lower and the puberty was significantly later in the prenatal group. Brain and ovary TOS and OSI values in the prenatal group were significantly increased (p < 0.05) compared to the control group. Serum LH levels of the prenatal and postnatal groups were increased, although serum FSH, and E2 values did not differ among the groups (p > 0.05). Histological examinations of the specimens revealed no statistically significant difference between the groups (p > 0.05). Exposure to 2450 MHz EMF, particularly in the prenatal period, resulted in postnatal growth restriction and delayed puberty in female Wistar rats. Increased TOS and OSI values in the brain and ovary tissues can be interpreted as a sign of chronic stress induced by EMF. This is the first longitudinal study which investigates the effects of EMF induced by wireless internet on pubertal development beside growth.


Enhancement of the reflectivity of Al/Zr multilayers by a novel structure.
The reflectivity of Al/Zr multilayers is enhanced by the use of a novel structure. The Al layers are divided by insertion of Si layers. In addition, Si barrier layers are inserted at the Al/Zr interfaces (Zr-on-Al and Al-on-Zr). As a result, crystallization of the Al layer is inhibited and that of Zr is enhanced. In grazing incidence x-ray reflectometry, x-ray diffraction, and extreme ultraviolet measurements, the novel multilayers exhibit lower interfacial roughness compared with traditional multilayer structures, and their reflectivity is increased from 48.2% to 50.0% at a 5° angle of incidence. These novel multilayers also have potential applications in other multilayer systems and the semiconductor industry.


[Outcomes of cardiac rehabilitation treatment and cost-effectiveness relations--A comparison between inpatient and outpatient rehabilitation programmes].
Regarding the dominance of inpatient medical rehabilitation programmes efforts have emerged over the last few years to strengthen outpatient medical rehabilitation programmes in Germany. The goal of cardiac rehabilitation is the recovery of physical, psychic and social wellbeing in people with a severe heart condition. For this contribution the central outcomes of cardiac rehabilitation were compared between different rehabilitation programmes (inpatient and outpatient) and cost-effectiveness analyses were made. These results were obtained within the scope of an evaluation study commissioned by the statutory health and pension insurance agency. In summary, the different rehabilitation programmes can be regarded as comparable concerning effectiveness and costs following rehabilitation.


Potent beta-lactam inhibitors of human cytomegalovirus protease.
A series of novel monobactam inhibitors of human cytomegalovirus (HCMV) protease has been described that possess a heterocyclic thiomethyl side chain at C-4. Changes to the heterocycle did not significantly change the inhibitory activity of these compounds in an enzymatic assay, although improvements in solubility and cell culture activity were noted. A number of permutations between C-4 substitutions and N-1 derivatives led to the identification of several beta-lactams with antiviral activity in a plaque reduction assay. N-methyl thiotetrazole-containing compounds were found to be the most potent inhibitors in the enzymatic assay.


Level of personality functioning as a predictor of psychosocial functioning-Concurrent validity of criterion A.
The alternative model for personality disorders (AMPD) in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), defines personality functioning by assessment of impairment in Identity and Self-direction (Self component) and in Empathy and Intimacy (Interpersonal). These four domains constitute the Level of Personality Functioning Scale, a trans-diagnostic measure of PD severity. The association between the Level of Personality Functioning Scale and psychosocial impairment based on other previously established psychosocial functioning instruments has not been reported. A total of 317 individuals, including a representative clinical sample of 282 patients (192 with a personality disorder [PD] diagnosis), was evaluated with the Structured Clinical Interview for the DSM-5 AMPD Module I. Self-reported impairment was measured by the Work and Social Adjustment Scale (WSAS), and social and occupational impairment was assessed by the functioning score of the Global Assessment of Functioning scale (GAF-F). WSAS and GAF-F both correlated significantly with mean LPFS scores and the sum of DSM-IV PD criteria. For both measures, the mean LPFS was a stronger predictor for psychosocial impairment than the sum of DSM-IV PD criteria. Within the LPFS, the Self component was a better predictor than the Interpersonal component for both WSAS and GAF-F. For the four domains, the results diverged, with Identity as the strongest predictor by far for WSAS. Empathy was the only significant predictor for impairment evaluated by GAF-F, but its contribution to variance was not substantial. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Pitx1 is necessary for normal initiation of hindlimb outgrowth through regulation of Tbx4 expression and shapes hindlimb morphologies via targeted growth control.
The forelimbs and hindlimbs of vertebrates are morphologically distinct. Pitx1, expressed in the hindlimb bud mesenchyme, is required for the formation of hindlimb characteristics and produces hindlimb-like morphologies when misexpressed in forelimbs. Pitx1 is also necessary for normal expression of Tbx4, a transcription factor required for normal hindlimb development. Despite the importance of this protein in these processes, little is known about its mechanism of action. Using a transgenic gene replacement strategy in a Pitx1 mutant mouse, we have uncoupled two discrete functions of Pitx1. We show that, firstly, this protein influences hindlimb outgrowth by regulating Tbx4 expression levels and that, subsequently, it shapes hindlimb bone and soft tissue morphology independently of Tbx4. We provide the first description of how Pitx1 sculpts the forming hindlimb skeleton by localised modulation of the growth rate of discrete elements.


Clarification of the factor structure of the 12-item General Health Questionnaire among Japanese adolescents and associated sleep status.
If the factors affecting the mental health status of adolescents and their association with sleep status could be clarified, this information would be helpful for formulating lifestyle and healthcare guidance for the promotion of healthy growth and the prevention of mental problems in these individuals. The purpose of this study was to clarify (1) the factor structure of the 12-item General Health Questionnaire (GHQ-12), and (2) the associations between the factors extracted from this questionnaire and lifestyle, in particular sleep status, by using a representative sample population of Japanese adolescents. One hundred three thousand sixty hundred fifty self-administered questionnaires were collected from students enrolled in junior high and high schools in Japan. Of these questionnaires, 99,668 were analyzed. Sleep duration, subjective sleep assessment, bedtime, and insomnia symptoms of these students over the past month were studied to investigate sleep status. The factor analyses yielded two factors: depression/anxiety and loss of positive emotion. Sleep duration of less than 7h was found to be associated with both depression/anxiety and loss of positive emotion, whereas sleep duration of 8h or more was associated only with loss of positive emotion. Subjective sleep assessment and insomnia symptoms were associated with both depression/anxiety and loss of positive emotion. It was demonstrated that two underlying factors of mental health status were associated with differences in sleep status. In order to improve the mental health status of adolescents, it is important to provide guidance about sleep and lifestyle habits according to the mental health status of the individual.


Posttraining Alpha Transcranial Alternating Current Stimulation Impairs Motor Consolidation in Elderly People.
The retention of a new sequential motor skill relies on repeated practice and subsequent consolidation in the absence of active skill practice. While the early phase of skill acquisition remains relatively unaffected in older adults, posttraining consolidation appears to be selectively impaired by advancing age. Motor learning is associated with posttraining changes of oscillatory alpha and beta neuronal activities in the motor cortex. However, whether or not these oscillatory dynamics relate to posttraining consolidation and how they relate to the age-specific impairment of motor consolidation in older adults remains elusive. Transcranial alternating current stimulation (tACS) is a noninvasive brain stimulation technique capable of modulating such neuronal oscillations. Here, we examined whether tACS targeting M1 immediately following explicit motor sequence training is capable of modulating motor skill consolidation in older adults. In two sets of double-blind, sham-controlled experiments, tACS targeting left M1 was applied at either 10 Hz (alpha-tACS) or 20 Hz (beta-tACS) immediately after termination of a motor sequence training with the right (dominant) hand. Task performance was retested after an interval of 6 hours to assess consolidation of the training-acquired skill. EEG was recorded over left M1 to be able to detect local after-effects on oscillatory activity induced by tACS. Relative to the sham intervention, consolidation was selectively disrupted by posttraining alpha-tACS of M1, while posttraining beta-tACS of M1 had no effect on delayed retest performance compared to the sham intervention. No significant postinterventional changes of oscillatory activity in M1 were detected following alpha-tACS or beta-tACS. Our findings point to a frequency-specific interaction of tACS with posttraining motor memory processing and may suggest an inhibitory role of immediate posttraining alpha oscillations in M1 with respect to motor consolidation in healthy older adults.


Segmentation decreases the magnitude of the tilt illusion.
In the tilt illusion, the perceived orientation of a target grating depends strongly on the orientation of a surround. When the orientations of the center and surround gratings differ by a small angle, the center grating appears to tilt away from the surround orientation (repulsion), whereas for a large difference in angle, the center appears to tilt toward the surround orientation (attraction). In order to understand how segmentation/perceptual grouping of the center and surround affect the magnitude of the tilt illusion, we conducted three psychophysical experiments in which we measured observers' perception of center orientation as a function of center-surround relative contrast, relative disparity depth, and geometric features such as occlusion and collinearity. All of these manipulations affected the strength of perceived orientation bias in the center. Our results suggest that if stronger segmentation/perceptual grouping is induced between the center and surround, the tilt repulsion bias decreases/increases. A grouping-dependent tilt illusion plays an important role in visual search and detection by enhancing the sensitivity of our visual system to feature discrepancies, especially in relatively homogenous environments.


[Mechanism of the stabilization of synaptosomes with alpha-tocopherol during activation of lipid peroxidation].
Using the fluorescent probe technique, it was shown that activation of lipid peroxidation decreases the value of transmembrane potential of rat brain synaptosomes. Depolarization of synaptosomes may be due to the impairment of the "barrier" properties of synaptosomal membranes and the decrease in Na,K-ATPase activity. alpha-Tocopherol and its model derivative devoid of the phytol chain--2,2,5,7,8-pentamethyl-6-oxychromanol--stabilize the transmembrane potential value during inhibition of lipid peroxidation. alpha-Tocopherol acetate causes no stabilizing or inhibiting effects. Unlike 2,2,5,7,8-pentamethyl-6-oxychromanol, alpha-tocopherol exerts a structuralizing action which manifests itself in the stabilization of the synaptosomal membrane potential during incomplete inhibition of lipid peroxidation. The previously established ability of alpha-tocopherol to protect synaptosomes from the damaging action of phospholipases and the experimental results of this work permit to regard vitamin E as a universal stabilizer of brain synaptosomal membranes.


[Robotic renal surgery: pyeloplasty].
The treatment of ureteropyelic junction (UPJ) obstruction offers a perfect sketch of the parallel evolution of the availability of technology and changes in surgical proceedings. From the open Anderson-Hynes pyeloplasty, passing through percutaneous or retrograde endopyelothomy with various instruments, to the laparoscopic approach, technology and human talent have found a field for development in this reconstructive procedure. Robotic surgery is young and starts to define its role in urology surgery. There are established procedures such as radical prostatectomy; it remains to be established what operations will benefit from the robotic technology, so results are under continuous evaluation. The non stopping advance of computer technology guarantees future achievements of robotic technology. The objective is to achieve that surgeons could perform difficult surgical procedures with a level of accuracy and clinical results that would be difficult to achieve with conventional methods. We analyze the technical features, results and comparative studies of the robotic pyeloplasty from the medical literature. Robotic surgery has demonstrated its usefulness in the performance of pyeloplasties, with good results in primary and secondary UPJ stenosis in children and adults, in various aetiologies. Robotics enables to diminish the difficulties of intracorporeal suture and the learning curve for surgeons without laparoscopic experience. Nevertheless, although initial clinical experience with robotic pyeloplasty is favourable, continuous evaluation of results is necessary to determine if the surgical procedure is as effective in the long-term as laparoscopic and open pyeloplasty.


Screening for asymptomatic bowel cancer in general practice.
General practitioners screened 4284 asymptomatic people aged over 40 to compare the incidence of large bowel cancer and polyps with a control general practice (4288 patients). Compliance was best in young women (60%), and overall it was 42%. Twenty six patients who had a positive Haemoccult test result (1.5% of those screened) were examined by colonoscopy and 10 had polyps. The incidence of cancers in the two groups was similar but in the control (unscreened patients) practice no polyps were found.


[Early results of the treatment of patients with recurrences of pulmonary tuberculosis].
Efficacy of treatment of 106 patients with destructive forms of recurring pulmonary tuberculosis is analysed. Treatment was conducted in comparable groups on 2 chemotherapeutic regimens. With regimen 1 consisting of a 4-drug combination, cavity closure was evident in 72.2%, while with regimen 2 including 3 drugs, cavities were closed in 42.3% of the cases. Cavity decay healing and bacteriostasis rates were higher for regimen 1 as compared to regimen 2, though the incidence of bacteriostasis was the same with both chemotherapeutic regimens, i.e. in 93.6% and in 92.8% with regimen 1 and 2, respectively. The incidence of side effects was practically unchanged in terms of the given chemotherapeutic regimen. A 4-drug combination should be chosen for the management of patients with destructive recurring pulmonary tuberculosis.


Use of qualitative methods in published health services and management research: a 10-year review.
Over the past 10 years, the field of health services and management research has seen renewed interest in the use of qualitative research methods. This article examines the volume and characteristics of qualitative research articles published in nine major health services and management journals between 1998 and 2008. Qualitative research articles comprise 9% of research articles published in these journals. Although the publication rate of qualitative research articles has not kept pace with that of quantitative research articles, citation analysis suggests that qualitative research articles contribute comparably to the field's knowledge base. A wide range of policy and management topics has been examined using qualitative methods. Case study designs, interviews, and documentary sources were the most frequently used methods. Half of qualitative research articles provided little or no detail about key aspects the study's methods. Implications are discussed and recommendations are offered for promoting the publication of qualitative research.


Protein synthesis editing by a DNA aptamer.
Potential errors in decoding genetic information are corrected by tRNA-dependent amino acid recognition processes manifested through editing reactions. One example is the rejection of difficult-to-discriminate misactivated amino acids by tRNA synthetases through hydrolytic reactions. Although several crystal structures of tRNA synthetases and synthetase-tRNA complexes exist, none of them have provided insight into the editing reactions. Other work suggested that editing required active amino acid acceptor hydroxyl groups at the 3' end of a tRNA effector. We describe here the isolation of a DNA aptamer that specifically induced hydrolysis of a misactivated amino acid bound to a tRNA synthetase. The aptamer had no effect on the stability of the correctly activated amino acid and was almost as efficient as the tRNA for inducing editing activity. The aptamer has no sequence similarity to that of the tRNA effector and cannot be folded into a tRNA-like structure. These and additional data show that active acceptor hydroxyl groups in a tRNA effector and a tRNA-like structure are not essential for editing. Thus, specific bases in a nucleic acid effector trigger the editing response.


Level crossing analysis of chemically induced dynamic nuclear polarization: Towards a common description of liquid-state and solid-state cases.
Chemically Induced Dynamic Nuclear Polarization (CIDNP) is an efficient method of creating non-equilibrium polarization of nuclear spins by using chemical reactions, which have radical pairs as intermediates. The CIDNP effect originates from (i) electron spin-selective recombination of radical pairs and (ii) the dependence of the inter-system crossing rate in radical pairs on the state of magnetic nuclei. The CIDNP effect can be investigated by using Nuclear Magnetic Resonance (NMR) methods. The gain from CIDNP is then two-fold: it allows one to obtain considerable amplification of NMR signals; in addition, it provides a very useful tool for investigating elusive radicals and radical pairs. While the mechanisms of the CIDNP effect in liquids are well established and understood, detailed analysis of solid-state CIDNP mechanisms still remains challenging; likewise a common theoretical frame for the description of CIDNP in both solids and liquids is missing. Difficulties in understanding the spin dynamics that lead to the CIDNP effect in the solid-state case are caused by the anisotropy of spin interactions, which increase the complexity of spin evolution. In this work, we propose to analyze CIDNP in terms of level crossing phenomena, namely, to attribute features in the CIDNP magnetic field dependence to Level Crossings (LCs) and Level Anti-Crossings (LACs) in a radical pair. This approach allows one to describe liquid-state CIDNP; the same holds for the solid-state case where anisotropic interactions play a significant role in CIDNP formation. In solids, features arise predominantly from LACs, since in most cases anisotropic couplings result in perturbations, which turn LCs into LACs. We have interpreted the CIDNP mechanisms in terms of the LC/LAC concept. This consideration allows one to find analytical expressions for a wide magnetic field range, where several different mechanisms are operative; furthermore, the LAC description gives a way to determine CIDNP sign rules. Thus, LCs/LACs provide a consistent description of CIDNP in both liquids and solids with the prospect of exploiting it for the analysis of short-lived radicals and for optimizing the polarization level.


Immunocytochemistry for SOX-11 and TFE3 as diagnostic markers for solid pseudopapillary neoplasms of the pancreas in FNA biopsies.
Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare malignant tumors that can be sampled via endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Although diagnosing SPNs can be straightforward in cases with a classic morphology and a typical immunoprofile, challenges can occur with morphologic variants or limited specimens. Recently, 2 immunohistochemical stains, SRY-related high-mobility group box 11 (SOX-11) and transcription factor E3 (TFE3), have been demonstrated to be highly sensitive and specific for SPNs in pancreatic resection specimens. The current study evaluates the diagnostic utility of these stains with EUS-FNA. Thirteen EUS-FNA specimens from SPNs with sufficient material for immunocytochemistry were identified from 2000 to 2016. These cases were compared with 13 EUS-FNA specimens of non-SPN pancreatic neoplasms. Immunocytochemistry for SOX-11, TFE3, and β-catenin was performed on all cell blocks and then was scored independently by 2 pathologists in a masked manner. Nuclear reactivity for SOX-11 was detected in 13 of 13 SPNs and in 0 of 13 non-SPNs; this resulted in sensitivity and specificity values of 100%, a positive predictive value (PPV) of 1, and a negative predictive value (NPV) of 1. Nuclear reactivity for TFE3 was detected in 9 of 13 SPNs and in 0 of 13 non-SPNs; this resulted in a sensitivity of 69.2%, a specificity of 100%, a PPV of 1, and an NPV of 0.765. Nuclear reactivity for β-catenin was detected in 13 of 13 SPNs and in 1 of 13 non-SPNs; this resulted in a sensitivity of 100%, a specificity of 92.3%, a PPV of 0.929, and an NPV of 1. SOX-11 is a sensitive and specific immunocytochemical stain for SPNs in EUS-FNA specimens, and it may be useful as a diagnostic marker for distinguishing SPNs from its cytologic mimics. Cancer Cytopathol 2017;125:831-7. © 2017 American Cancer Society.


Linezolid Population Pharmacokinetics in South African Adults with Drug-Resistant Tuberculosis.
Linezolid is widely used for drug-resistant tuberculosis (DR-TB) but has a narrow therapeutic index. To inform dose optimization, we aimed to characterize the population pharmacokinetics of linezolid in South African participants with DR-TB and explore the effect of covariates, including HIV coinfection, on drug exposure. Data were obtained from pharmacokinetic substudies in a randomized controlled trial and an observational cohort study, both of which enrolled adults with drug-resistant pulmonary tuberculosis. Participants underwent intensive and sparse plasma sampling. We analyzed linezolid concentration data using nonlinear mixed-effects modeling and performed simulations to estimate attainment of putative efficacy and toxicity targets. A total of 124 participants provided 444 plasma samples; 116 were on the standard daily dose of 600 mg, while 19 had dose reduction to 300 mg due to adverse events. Sixty-one participants were female, 71 were HIV-positive, and their median weight was 56 kg (interquartile range [IQR], 50 to 63). In the final model, typical values for clearance and central volume were 3.57 liters/h and 40.2 liters, respectively. HIV coinfection had no significant effect on linezolid exposure. Simulations showed that 600-mg dosing achieved the efficacy target (area under the concentration-time curve for the free, unbound fraction of the drug [[Formula: see text] at a MIC level of 0.5 mg/liter) with 96% probability but had 56% probability of exceeding safety target ([Formula: see text]. The 300-mg dose did not achieve adequate efficacy exposures. Our model characterized population pharmacokinetics of linezolid in South African patients with DR-TB and supports the 600-mg daily dose with safety monitoring.


Anti-inflammatory and chondroprotective effects of nutraceuticals from Sasha's Blend in a cartilage explant model of inflammation.
New Zealand green lipped mussel (NZGLM), abalone (AB), and shark cartilage (SC) are extensively used for treatment of and/or as preventatives for arthritis, despite a relative paucity of scientific evidence for efficacy. This research integrated a simulated digestion protocol with ultrafiltration and cartilage explants to generate new information on the anti-inflammatory and chondroprotective properties of NZGLM, SC, and AB. Each nutraceutical was artificially digested using simulated gastric and intestinal fluids, and the crude digest was ultrafiltered (50 kDa). Each filtrate was applied individually to cartilage explants before the explants were stimulated with IL-1 to induce an acute inflammatory response. Media were collected daily for 48 h and analyzed for prostaglandin E(2) (PGE(2)), glycosaminoglycan (GAG), and nitric oxide (NO), and cartilage tissue was differentially stained to determine the relative proportion of live and dead cells. SC and NZGLM significantly inhibited IL-1-induced PGE(2) synthesis and IL-1-induced GAG release, and AB was an effective inhibitor of IL-1-induced NO production. The three test nutraceuticals affect at least three major pathways involved in the catabolic cycle of arthritis and may prove important treatments and/or preventatives for the pain and degradation associated with this condition. The methodology and results describe a useful model for evaluating dietary nutraceuticals in vitro.


Bases for interactions between saflufenacil and glyphosate in plants.
Buckwheat (Fagropyrum esculentum Moench.), cabbage (Brassica oleracea L), and conventional and glyphosate-resistant varieties of canola (Brassica napus L.) were used to study the bases of saflufenacil and glyphosate interactions. Compared to the addition of Merge (surfactant), the addition of both Transorb (i.e., commercial product, Transorb formulation with glyphosate) and Merge increased the cuticular absorption of [(14)C] saflufenacil in cabbage plants with thick epicuticular wax layers. However, in all cases, the addition of glyphosate reduced the translocation of [(14)C]saflufenacil in glyphosate-susceptible plants, while translocation was not affected in glyphosate-resistant canola. Moreover, the phytotoxicity of saflufenacil reduced the activity of glyphosate, possibly by reducing its translocation in all plant species studied. Increased absorption of saflufenacil by the addition of Transorb (i.e., Transorb formulation with glyphosate) plus Merge appears to increase its contact activity, thus the interaction of saflufenacil and glyphosate involves two separate processes, absorption and translocation.


The effects of ketotifen on beta-adrenergic activity in asthmatics.
In order to examine a possible mechanism of action of ketotifen in asthma, a double-blind study was undertaken to determine whether ketotifen showed any effects on the beta-adrenergic system in asthmatic patients. The effects of ketotifen 1 mg b.i.d. for one month on the changes in spirometry, plasma potassium and serum glucose nebulized salbutamol was compared with placebo. In addition the degree of inhibition caused by local salbutamol on the wheal volume due to intradermal prostaglandin E and bradykinin, was compared following ketotifen and placebo. Nebulized salbutamol produced consistent improvements in spirometry and changes in potassium and glucose levels. Local salbutamol significantly decreased the wheal volume induced by intradermal prostaglandin E and bradykinin. However, none of these salbutamol-induced effects were altered following ketotifen or placebo. Ketotifen, in the doses used, has no demonstrable effect on the beta-adrenergic system in asthmatic patients.


Relation of neuroleptic dose and tardive dyskinesia to attention, information-processing, and psychophysiology in medicated schizophrenics.
Relationships of neuroleptic dosage and tardive dyskinesia with measures of attentional, information-processing, and psychophysiological dysfunctions in medicated chronic schizophrenics were explored by correlational and stepwise multiple-regression analysis. High neuroleptic dosage was found to be associated with increased reaction time, reduced span of apprehension, low basal skin conductance level, and reduced skin conductance reactivity. Severe abnormal involuntary movements were associated with increased eye-tracking dysfunction, increased scanning eye-movement rate, increased reaction time, and reduced skin conductance reactivity. These findings led to the hypothesis that neuroleptic dosage and tardive dyskinesia may be sources of error variance in the measurement of attentional, information-processing, and psychophysiological functions in schizophrenics.


Enhanced Stability and Oral Bioavailability of Cannabidiol in Zein and Whey Protein Composite Nanoparticles by a Modified Anti-Solvent Approach.
Wide applications of cannabidiol (CBD) in the food and pharmaceutical industries are limited due to its low bioavailability, sensitivity to environmental pressures and low water solubility. Zein nanoparticles were stabilized by whey protein (WP) for the delivery of cannabidiol (CBD) using a modified anti-solvent approach. Particle size, surface charge, encapsulation efficiency, and re-dispersibility of nanoparticles were influenced by the zein to WP ratio. Under optimized conditions at 1:4, zein-WP nanoparticles were fabricated with CBD (200 μg/mL) and further characterized. WP absorbed on zein surface via hydrogen bond, hydrophobic forces, and electrostatic attraction. The zein-WP nanoparticles showed excellent storage stability (4 °C, dark) and effectively protected CBD degradation against heat and UV light. In vivo pharmacokinetic study demonstrated that CBD in zein-WP nanoparticles displayed 2-times and 1.75-fold enhancement in maximum concentration (C max) and the area under curve (AUC) as compared to free-form CBD. The data indicated the feasibility of developing zein-WP based nanoparticles for the encapsulation, protection, and delivery of CBD.


Solubilization and delivery by GroEL of megadalton complexes of the lambda holin.
GroEL can solubilize membrane proteins by binding them in its hydrophobic cavity when detergent is removed by dialysis. The best-studied example is bacteriorhodopsin, which can bind in the GroEL chaperonin at two molecules per tetradecamer. Applying this approach to the holin and antiholin proteins of phage lambda, we find that both proteins are solubilized by GroEL, in an ATP-sensitive mode, but to vastly different extents. The antiholin product, S107, saturates the chaperonin at six molecules per tetradecameric complex, whereas the holin, S105, which is missing the two N-terminal residues of S107, forms a hyper-solubilization complex with up to 350 holin molecules per GroEL, or approximately 4 MDa of protein per 0.8 MDa tetradecamer. Gel filtration chromatography and immunoprecipitation experiments confirmed the existence of complexes of the predicted masses for both S105 and S107 solubilization. For S105, negatively stained electron microscopic images show structures consistent with protein shells of the holin assembled around the chaperonin tetradecamer. Importantly, S105 can be delivered rapidly and efficiently to artificial liposomes from these complexes. In these delivery experiments, the holin exhibits efficient membrane-permeabilizing activity. The S107 antiholin can block formation of the hypersolubilization complexes, suggesting that their formation is related to an oligomerization step intrinsic to holin function.


Effect of traumatic brain injury among U.S. servicemembers with amputation.
Servicemembers with combat-related limb loss often require substantial rehabilitative care. The prevalence of traumatic brain injury (TBI), which may impair cognitive and functional abilities, among servicemembers has increased. The primary objectives of this study were to determine the frequency of TBI among servicemembers with traumatic amputation and examine whether TBI status was associated with discharge to civilian status and medical and rehabilitative service use postamputation. U.S. servicemembers who had a combat-related amputation while deployed in Iraq or Afghanistan between 2001 and 2006 were followed for 2 yr postamputation. Data collected includes injury mechanism; postinjury complications; Injury Severity Score (ISS); and follow-up data, including military service discharge status and number of medical, physical, occupational therapy, and prosthetic-related visits. Of the 546 servicemembers with combat-related amputations, 127 (23.3%) had a TBI diagnosis. After adjusting for ISS and amputation location, those with TBI had a significantly greater mean number of medical and rehabilitative outpatient and inpatient visits combined (p < 0.01). Those with TBI were also at greater odds of developing certain postinjury complications. We recommend that providers treating servicemembers with limb loss should assess for TBI because those who sustained TBI required increased medical and rehabilitative care.


Oestrogen receptor alpha localisation in the prefrontal cortex of three mammalian species.
Oestrogen modulates cognitive function and affective behaviours subserved by the prefrontal cortex (PFC). Identifying and localising oestrogen receptor (ER)alpha, in human PFC will contribute to our understanding of the molecular mechanism of oestrogen action in this region. Inferences about the site of action of oestrogen in human brain are derived largely from studies performed in nonhuman mammalian species; however, the congruence of findings across species has not been demonstrated. Furthermore, the laminar, cellular, and subcellular localisation of ERalpha in the cortex is debated. Therefore, we compared the distribution of ERalpha in human dorsolateral prefrontal cortex (DLPFC) with that of monkey DLPFC and rat medial PFC. Immunohistochemistry performed on frontal cortex from the three species demonstrated ERalpha positive cells throughout all layers of the PFC, in pyramidal and nonpyramidal neurones, with both nuclear and cytoplasmic immunoreactivity. Western blot analyses and preabsorption studies confirmed that the antibody used recognised ERalpha and not ERbeta. A strong ERalpha immunoreactive band corresponding to the full-length ERalpha protein (65-67 kDa) in the frontal cortex of all three species matched the size of the predominant immunoreactive band detected in breast cancer cell lines known to express ERalpha. Additionally, other ERalpha immunoreactive proteins of varying molecular weight in breast cancer cells, rat ovary and mammalian brain were detected, suggesting that ERalpha may exist in more than one form in the mammalian frontal cortex. The present study provides evidence that ERalpha protein exists in neurones in mammalian PFC and that ERalpha is anatomically well-positioned to directly mediate oestrogen action in these neurones.


In vitro synthesis of the first dipeptide of the beta subunit of Escherichia coli RNA polymerase.
Plasmids pNF1337 and pNF1341, which contain part of the L10 operon including the RNA polymerase beta-subunit gene, have been used as templates in vitro to investigate expression of the beta-subunit gene. For these studies, the synthesis of the first dipeptide of the beta subunit, fMet-Val, was measured instead of that of the entire protein. By using this dipeptide system, we studied the effects of RNA polymerase holoenzyme and L factor (nus A gene product) on fMET-Val synthesis and compared the relative effects of the primary and secondary promoters in the L10 operon on expression of the beta-subunit gene. The results show that the inhibitory effect of RNA polymerase on beta-subunit synthesis and the stimulatory effect of L factor occur before formation of the first dipeptide bond. In this in vitro system, the secondary promoters account for about 50% of the total fMet-Val synthesized. Although the primary promoter is sensitive to guanosine 5'-diphosphate 3'-diphosphate in vitro, the secondary promoters are not affected by this nucleotide.


Studies on the mechanism of the formation of the penicillin antigen. I. Delayed allergic cross-reactions among penicillin G and its degradation products.
Seven highly purified degradation products of penicillin G (PG) were examined with regard to their ability to cross-react allergically with PG. Guinea pig allergic contact dermatitis was employed as the test system. Three of these degradation products, D-benzylpenicillenic acid (BPE), D-penicillamine, and D-alpha-benzylpenicilloic acid were found to cross-react with PG and also to be capable of inducing delayed contact allergy in the guinea pig. BPE and PG cross-reacted with particularly intense reactions, and other immunologic experiments indicated that PG and BPE introduce identical allergic determinant groups into epidermal proteins. These experimental results were correlated with the results of previous studies concerning the degradation pathways of PG under physiological conditions in vitro, and the chemical reactivities of these degradation products. Based on these immunologic and chemical data, a schema is proposed which suggests the chemical pathways by which PG may react with epidermal proteins in vivo to form the penicillin antigen. The identity of the specific antigenic determinant groups of the penicillin antigen is suggested. The relationship between PG allergy of the contact dermatitis type in the guinea pig and PG allergy of the immediate type in man is discussed.


Expansive Laminoplasty Versus Laminectomy Alone Versus Laminectomy and Fusion for Cervical Ossification of the Posterior Longitudinal Ligament: Is There a Difference in the Clinical Outcome and Sagittal Alignment?
Intervention comparison study. To assess postoperative cervical lordosis, clinical outcome, and progression of ossification of the posterior longitudinal ligament (OPLL) in patient of cervical spondylotic myelopathy (CSM) by the OPLL. The posterior approach is usually used for multilevel (≥3) CSM and is decided based on cervical lordosis and instability. OPLL, 1 cause of CSM, makes decreased neck motion and is progressed by neck motion. In OPLL patients, it may be asked whether motion-preserving surgery is still helpful. We reviewed 57 patients of CSM by OPLL who underwent 3 posterior surgeries, laminoplasty, laminectomy alone (LA), and laminectomy with fusion (LF), and followed up minimum 24 months. Postoperative cervical sagittal balance was measured using by the C2-C7 sagittal vertical axis (SVA), cervical curvature index, and C2-C7 Cobb angle. The clinical outcome was analyzed by the neck disability index and the visual analog scale for axial pain. OPLL progression was measured by length and depth growth. A linear mixed model was used to evaluate the differences between each time point and baseline score. Cervical lordosis, C2-C7 Cobb angle, and cervical curvature index decreased gradually in all patients. SVA was maintained in the LF group only and increased in the others (P=0.01). Clinical outcomes, neck disability index, and visual analogue scale were evenly improved in all groups. In patients showing SVA≥40 mm at baseline, neck pain increased in the laminoplasty group but was stationary in the LF group. Progression of OPLL was observed more frequent in the LA group than in the LF group. Posterior surgeries resulted in clinical improvements although with loss of cervical lordosis in CSM with OPLL patients. OPLL may worsen more frequently after LA. LF and laminoplasty are preferable techniques in this condition, with the former better for patients with high baseline SVA distances.


The dawning of a new age of toxicology.
Toxicology faces enormous challenges in a world in which we are exposed to thousands of chemicals and millions of mixtures thereof. Radically new approaches to this problem need to be developed. A milestone in this direction is the vision of the US National Research Council (NRC) "Toxicity testing in the 21st century: a Vision and a Strategy". Currently, an alliance formed by the National Toxicology Program (NTP) and the Chemical Genomics Centre (NCGC) of the National Institutes of Health (NIH) and the Computational Toxicology Centre (NCCT) of the Environmental Protection Agency (EPA) is testing whether this new strategy can realistically form the basis of future public health decisions. The vision requires a radical paradigm shift in the approach to safety assessments, and turns the traditional procedures upside down. Where animal experiments used to be the most important technology, the future is seen in the strength of in vitro and in silico approaches based on human material. Today's toxicity testing starts with an initial black box screen on animals, sometimes followed by mechanistic studies, while the new vision approaches hazard assessment bottom-up. The procedure would begin with in vitro tests to define the affected pathways. To fill remaining gaps of knowledge, limited and targeted testing in animals would then be performed as a possible second step. This means nothing less than changing toxicology from being a predominantly observational craft and regulatory support discipline back to a natural science with all its dimensions. The background and the implications are discussed here in particular for a readership with interest also in parallel European trends.


Home care as reablement or enabling arrangements? An exploration of the precarious dependencies in living with functional decline.
The threat to welfare societies posed by population ageing has urged high-income countries to rethink the provision of social and healthcare services for the ageing population. One widely implemented policy solution is 'reablement': short-term home-based training programmes focusing on re-enabling older people to carry out activities of daily living independently. Drawing on empirical material from multisited ethnographic fieldwork of reablement practices in a Danish municipality we explore how the assumptions about independence embedded in the concept's linguistic parts - 're', 'able' and 'ment' - map onto lives characterised by functional decline. We find that home care applicants: (i) are often too deeply dependent on the capacities of others in order to have their independence restored; (ii) negotiate individual meanings of independence to maintain their identity as able human beings; and (iii) might possibly gain new capacities through reablement, yet these are not individual and stable achievements, but rather temporary effects of the care relations with eldercare professionals. Rather than reablement we, therefore, suggest the term 'enabling arrangements' as more appropriate for capturing independence as a distributed, negotiated and continuous accomplishment. Finally, we discuss the practical and ethical implications of this term.


Measurement and modeling of ozone and nitrogen oxides produced by laser breakdown in oxygen-nitrogen atmospheres.
The production of ozone nad nitrogen oxides was studied during multiple laser breakdown in oxygen-nitrogen mixtures at atmospheric pressure. About 2000 laser shots at 10(10) W cm-2 were delivered into a sealed reaction chamber. The chamber with a long capillary was designed to measure absorption of O3, NO, and NO2 as a function of the number of laser shots. The light source for absorption measurements was the continuum radiation emitted by the plasma during the first 0.2 microsecond of its evolution. A kinetic model was developed that encompassed the principal chemical reactions between the major atmospheric components and the products of laser breakdown. In the model, the laser plasma was treated as a source of nitric oxide and atomic oxygen, whose rates of production were calculated using measured absorption by NO, NO2, and O3. The calculated concentration profiles for NO, NO2, and O3 were in good agreement with measured profiles over a time scale of 0-200 s. The steady-state concentration of ozone was measured in a flow cell in air. For a single breakdown in air, the estimated steady-state yield of ozone was 2 x 10(12) molecules, which agreed with the model prediction. This study can be of importance for general understanding of laser plasma chemistry and for elucidating the nature of spectral interferences and matrix effects that may take place in applied spectrochemical analysis.


Vacancy-Induced Synaptic Behavior in 2D WS2 Nanosheet-Based Memristor for Low-Power Neuromorphic Computing.
Memristors with nonvolatile memory characteristics have been expected to open a new era for neuromorphic computing and digital logic. However, existing memristor devices based on oxygen vacancy or metal-ion conductive filament mechanisms generally have large operating currents, which are difficult to meet low-power consumption requirements. Therefore, it is very necessary to develop new materials to realize memristor devices that are different from the mechanisms of oxygen vacancy or metal-ion conductive filaments to realize low-power operation. Herein, high-performance and low-power consumption memristors based on 2D WS2 with 2H phase are demonstrated, which show fast ON (OFF) switching times of 13 ns (14 ns), low program current of 1 µA in the ON state, and SET (RESET) energy reaching the level of femtojoules. Moreover, the memristor can mimic basic biological synaptic functions. Importantly, it is proposed that the generation of sulfur and tungsten vacancies and electron hopping between vacancies are dominantly responsible for the resistance switching performance. Density functional theory calculations show that the defect states formed by sulfur and tungsten vacancies are at deep levels, which prevent charge leakage and facilitate the realization of low-power consumption for neuromorphic computing application.


Two-dimensional density-matrix topological fermionic phases: topological Uhlmann numbers.
We construct a topological invariant that classifies density matrices of symmetry-protected topological orders in two-dimensional fermionic systems. As it is constructed out of the previously introduced Uhlmann phase, we refer to it as the topological Uhlmann number n_{U}. With it, we study thermal topological phases in several two-dimensional models of topological insulators and superconductors, computing phase diagrams where the temperature T is on an equal footing with the coupling constants in the Hamiltonian. Moreover, we find novel thermal-topological transitions between two nontrivial phases in a model with high Chern numbers. At small temperatures we recover the standard topological phases as the Uhlmann number approaches to the Chern number.


Two-dimensional echocardiographic assessment of mitral stenosis.
A real-time, phased-array, two-dimensional echocardiography system was used to assess mitral valve motion in 30 catheterized patients with pure mitral stenosis. Suitable images for analysis of mitral valve motion were obtained in 25 patients. The valve leaflets were most thickened and immobile at the leaflet tips while maximum mobility was at the leaflet body. Diastolic movement of anterior mitral leaflet toward the septum pulled the posterior mitral leaflet mid-portion inferiorly. Systolic bulging of the mid-portion of the anterior mitral leaflet into the left atrium was seen in 40% (10 of 25). Movement of the anterior mitral leaflet in diastole is primarily due to movement of the whole mitral apparatus in patients with mitral stenosis. The anterior mitral leaflet E to F slopes did not correlate (r=0.38) with the mitral valve area determined at catheterization. Planimetry of the mitral valve area directly from the videotape images compared favorably to the valve area determined at catheterization (r=0.95). Thus, mitral valve area determined by this technique is an accurate noninvasive method for assessing the severity of mitral stenosis.¿


Isolation and characterization of a mouse cDNA clone that expresses mast-cell growth-factor activity in monkey cells.
A cDNA sequence coding for mouse mast-cell growth-factor (MCGF) has been cloned from a cDNA library prepared from mRNA derived from a concanavalin A-activated mouse T-cell clone. Cloning was achieved using the pcD vector that permits expression of cDNA inserts in mammalian cells. The DNA sequence codes for a polypeptide of 166 amino acid residues including a putative signal peptide. The supernatant fluid obtained after transfection of COS-7 monkey cells with the pcD-MCGF plasmid had mouse MCGF activity. The MCGF amino acid sequence between amino acids 33 and 41, deduced from the nucleotide sequence of its cDNA, is identical to the NH2-terminal sequence of the mouse lymphokine, interleukin 3, suggesting that MCGF is related to interleukin 3.


Correlation of lens density measured using the Pentacam Scheimpflug system with the Lens Opacities Classification System III grading score and visual acuity in age-related nuclear cataract.
To investigate the relationship between lens density measured with the Pentacam Scheimpflug System and grading score using the Lens Opacities Classification System (LOCS) III as well as that between lens density and visual acuity in age-related nuclear cataract patients. Lens density and grading score were evaluated in 138 cases (180 eyes) with age-related nuclear cataract. LogMAR visual acuity was tested with the Early Treatment Diabetic Retinopathy Study chart. The correlations between lens density value and LOCS III nuclear opacity (NO) and nuclear colour (NC) grading score and that between lens density value and logMAR visual acuity were analysed. There was a linear increasing relationship between lens density value and LOCS III grading score in nuclear cataract patients. Lens density value had a stronger significant correlation with LOCS III NO score than that with NC score. The correlation between the nuclear lens density value and logMAR visual acuity was stronger than that between NO score and logMAR visual acuity or between NC score and logMAR visual acuity. Lens density as a quantitative and objective parameter can present the degree of NO and associated visual impairment due to nuclear cataract. The LOCS III criterion as an economic cataract grading system provides data that are in satisfactory concordance with the results obtained using the Pentacam Scheimpflug system.


Memory impairment and awareness of memory deficits in early-stage Alzheimer's disease.
In addition to their memory impairment, individuals with Alzheimer's disease (AD) often suffer from deficits in self-awareness. Awareness of memory deficits or metamemory is a multifaceted function, comprising on-line self-monitoring, generalized self-beliefs of memory efficacy, and generalized knowledge about memory functions. Awareness of memory problems in early-stage AD is a matter of clinical importance from a humanistic point of view, because higher levels of awareness may be associated with better future outcomes. Current methods of measuring awareness tend to fall into two categories, i.e., to introduce a questionnaire assessing patient/caregiver discrepancies; or to ask a patient to prospectively predict or retrospectively postdict their own memory performances. Characteristics of each measure as well as relationship between the two measures were discussed. For the performance prediction/postdiction paradigm, we used recognition memory of auditory verbal learning tests and awareness of memory deficits were examined in 24 individuals with early-stage AD. In addition to their significantly impaired recognition memory, individuals with AD displayed underawareness of memory deficits even at this early stage. They retrospectively overestimated memory performance after actual performance, but appeared to benefit from feedback and displayed intact on-line awareness of memory dysfunction, leading to normal prediction of the second session. However, individuals with AD again failed to retrospectively incorporate incidents of memory failure into generalized self-belief systems. Brain/behavior correlational analyses suggest that the prefrontal cortex and posterior dorsomedial regions including the precuneus may be involved in self-awareness.


The bactericidal effect of isoascorbic acid combined with mild heat.
The thermal inactivation of Salmonella thompson, Escherichia coli, Staphylococcus aureus, Clostridium perfringens, Candida zeylanoides, Enterococcus faecium and E. faecalis was accelerated by the addition of sodium isoascorbate (1 mmol/l) to phosphate-buffer heating medium but not to complex food mixtures. The lethal effect of isoascorbate was nullified by heating under anaerobic conditions or by the addition of catalase. The scavengers of hydroxyl radicals, mannitol and formate were not protective whereas histidine was. Histidine may have protected by slowing the rate of isoascorbate autoxidation, a property common to other amino acids tested. Superoxide dismutase was not protective. Dehydroascorbic acid also enhanced heat killing and its action was also reversed by catalase. The bactericidal effects of mild heat plus isoascorbate or dehydroascorbic acid both apparently depend on oxidative processes but their relative effectiveness was not related to their respective rates of oxygen consumption or peroxide production. We speculate that site-specific redox reactions, involving amino-carbonyl intermediates are involved in the inactivation mechanism.


Statistical fragility analysis of reported outcomes associated with surgical management of acetabular labral pathology.
The purpose of this study was to analyse the robustness of comparative research that evaluated arthroscopic labral reconstruction versus other surgical management of labral pathology. Key measures of statistical fragility include the fragility index and fragility quotient.ß. 12 comparative studies that evaluated the use of arthroscopic labral reconstruction were included in this study. Particular attention was placed on evaluating trends, either statistically significant or not, of functional improvement, complication rates, need for total hip arthroplasty (THA) and revision rates with associated p-values. The analysis involved in this study was the Fragility Index, which is the median number of events required to change the statistical significance of a particular outcome, thus changing the study conclusions. Fragility quotient was calculated for each study as the fragility index divided by sample size. Of the 12 studies that were included for analysis, there were a total of 25 reported outcomes, 8 of which were statistically significant (p < 0.05). The statistical fragility for the significant outcomes were 2.5 (interquartile range [IQR]: 1.5-3.5), whereas the median statistical fragility for insignificant results was 6 (IQR 4-9). The overall fragility index was 4 (IQR 3-7). The median of fragility quotients was 0.04 (IQR 0.01-0.07). This study demonstrated that comparative research regarding arthroscopic techniques of labral reconstruction may not be as statistically stable as previously hoped. In many of the reported outcomes, particularly the ones that were statistically significant, only a small percentage of event changes was required to change the significance of the study conclusions. This fragility is worrisome, since clinical decisions that rely on these reported outcomes may have a significant impact on long-term patient outcomes. It is, therefore, crucial to optimise patient outcomes by incorporating past literature and reported outcomes.


Assessment of the Contribution of a Thermodynamic and Mechanical Destabilization of Myosin-Binding Protein C Domain C2 to the Pathomechanism of Hypertrophic Cardiomyopathy-Causing Double Mutation MYBPC3Δ25bp/D389V.
Mutations in the gene encoding cardiac myosin-binding protein-C (MyBPC), a thick filament assembly protein that stabilizes sarcomeric structure and regulates cardiac function, are a common cause for the development of hypertrophic cardiomyopathy. About 10% of carriers of the Δ25bp variant of MYBPC3, which is common in individuals from South Asia, are also carriers of the D389V variant on the same allele. Compared with noncarriers and those with MYBPC3Δ25bp alone, indicators for the development of hypertrophic cardiomyopathy occur with increased frequency in MYBPC3Δ25bp/D389V carriers. Residue D389 lies in the IgI-like C2 domain that is part of the N-terminal region of MyBPC. To probe the effects of mutation D389V on structure, thermostability, and protein-protein interactions, we produced and characterized wild-type and mutant constructs corresponding to the isolated 10 kDa C2 domain and a 52 kDa N-terminal fragment that includes subdomains C0 to C2. Our results show marked reductions in the melting temperatures of D389V mutant constructs. Interactions of construct C0-C2 D389V with the cardiac isoforms of myosin-2 and actin remain unchanged. Molecular dynamics simulations reveal changes in the stiffness and conformer dynamics of domain C2 caused by mutation D389V. Our results suggest a pathomechanism for the development of HCM based on the toxic buildup of misfolded protein in young MYBPC3Δ25bp/D389V carriers that is supplanted and enhanced by C-zone haploinsufficiency at older ages.


Deuterium oxide as a contrast medium for real-time MRI-guided endovascular neurointervention.
Rationale: Endovascular intervention plays an important role in the treatment of various diseases, in which MRI-guidance can potentially improve precision. However, the clinical applications of currently available contrast media, including Gadolinium-based contrast agents and superparamagnetic iron oxide particles (SPIO), are hindered by safety concerns. In the present study, we sought to develop D2O as a novel contrast agent for guiding endovascular neurointervention. Methods: Animal studies were approved by institutional ACUC and conducted using an 11.7 T Bruker Biospec system and a 3T Siemens Trio clinical scanner for rodent and canine imaging, respectively. The locally selective blood brain barrier opening (BBBO) in rat brains was obtained by intraarterial (IA) injection of mannitol. The dynamic T2w* EPI MRI sequence was used to study the trans-catheter perfusion territory by IA administered SPIO before mannitol administration, whereas a dynamic T1w FLASH sequence was used to acquire Gd contrast-enhanced MRI for assessing BBBO after injection of mannitol. The contrast generated by D2O assessed by either EPI or FLASH methods was compared with the corresponding results assessed by SPIO or Gd. The utility of D2O MRI was also demonstrated to guide drug delivery to glioma in a mouse model. Finally, the clinical utility of D2O-MRI was demonstrated in a canine model. Results: Our study has shown that the contrast generated by D2O can be used to precisely delineate trans-catheter perfusion territory in both small and large animals. The perfusion territories determined by D2O-MRI show moderate correlation with those by SPIO-MRI (Spearman coefficient r = 0.5234, P < 0.001). Moreover, our results show that the perfusion territory determined by D2O-MRI can successfully predict the areas with BBBO after mannitol treatment similar to that assessed by Gd-MRI (Spearman coefficient r = 0.6923, P < 0.001). Using D2O-MRI as imaging guidance, the optimal infusion rate in the mouse brain was determined to be 150 µL/min to maximize the delivery efficacy to the tumor without serious off-target delivery to the brain parenchyma. The enhanced drug delivery of antibodies to the brain tumor was confirmed by fluorescence imaging. Conclusion: Our study demonstrated that D2O can be used as a negative MRI contrast medium to guide endovascular neurointervention. The established D2O -MRI method is safe and quantitative, without the concern of contrast accumulation. These qualities make it an attempting approach for a variety of endovascular procedures.


Effectiveness of brief intervention and contact for suicide attempters: a randomized controlled trial in five countries.
To determine whether brief intervention and contact is effective in reducing subsequent suicide mortality among suicide attempters in low and middle-income countries. Suicide attempters (n = 1867) identified by medical staff in the emergency units of eight collaborating hospitals in five culturally different sites (Campinas, Brazil; Chennai, India; Colombo, Sri Lanka; Karaj, Islamic Republic of Iran; and Yuncheng, China) participated, from January 2002 to October 2005, in a randomized controlled trial to receive either treatment as usual, or treatment as usual plus brief intervention and contact (BIC), which included patient education and follow-up. Overall, 91% completed the study. The primary study outcome measurement was death from suicide at 18-month follow-up. Significantly fewer deaths from suicide occurred in the BIC than in the treatment-as-usual group (0.2% versus 2.2%, respectively; chi2 = 13.83, P < 0.001). This low-cost brief intervention may be an important part of suicide prevention programmes for underresourced low- and middle-income countries.


Symmetry of septin hourglass and ring structures.
Septin filaments form ordered hourglass and ring-shaped structures in close apposition to the yeast bud-neck membrane. The septin hourglass scaffolds the asymmetric localization of many essential cell division proteins. However, it is unknown whether the septin structures have an overall polarity along the mother-daughter axis that determines the asymmetric protein localization. Here we engineered rigid septin- green fluorescent protein (GFP) fusions with various fluorescence dipole directions by changing the position of the GFP beta-barrel relative to the septin filament axis. We then used polarized fluorescence microscopy to detect potential asymmetries in the filament organization. We found that both the hourglass and ring filament assemblies have sub-resolution C(2) symmetry and lack net polarity along the mother-daughter axis. The hourglass filaments have an additional degree of symmetry relative to the ring filaments, most likely due to a twist in their higher-order structure. We previously reported that during the hourglass to rings transition septin filaments change their direction. Here we show that the filaments also undergo a change in their lateral organization, consistent with filament untwisting. The lack of net septin polarity along the mother-daughter axis suggests that there are no septin-based structural reasons for the observed asymmetry of other proteins. We discuss possible anisotropic processes that could break the septin symmetry and establish the essential bud-neck asymmetry.


What physician executives and health care organizations should expect from each other.
Today, interest in defining the role of the physician executive and ensuring this individual is effectively integrated into the organization is high for good reason--the ranks of physician executives are growing. What attributes should health care organizations look for when hiring physician executives and what should they should expect of them once they are on the job? Physician executives should: (1) have demonstrated clinical and management skills; (2) have a comfort level with participatory decision-making; (3) have superb interpersonal skills; and (4) be a champion of the patient. Physician executives should expect the following support from their organizations: (1) varied roles and responsibilities; (2) mentoring by other senior executives; (3) lifelong learning opportunities; and (4) complete support of the management team.


Evolution and mammalian dental morphology.
Evidence for the action of natural selection on the mammalian dentition is reviewed. Dental variation largely reflects genetical differences, but environmental factors have a significant effect, especially on the later developing teeth. Reduction of dental variance with age provides direct evidence of selection, but most evidence consists of demonstrations of adaptiveness. Dental adaptation is partly external, mainly to the food, and partly internal, resulting in the functional integration of teeth with each other, as in occlusal relations, and with the neuromuscular system responsible for jaw movements. Ontogeny is also adapted to produce a functional end-product. Most interspecific differences have not yet been explained in terms of function, and many of them may be due to drift.


Cellular HIV-1 DNA levels in patients receiving antiretroviral therapy strongly correlate with therapy initiation timing but not with therapy duration.
Viral reservoir size refers to cellular human immunodeficiency virus-1 (HIV-1) DNA levels in CD4(+) T lymphocytes of peripheral blood obtained from patients with plasma HIV-1-RNA levels (viral load, VL) maintained below the detection limit by antiretroviral therapy (ART). We measured HIV-1 DNA levels in CD4(+) lymphocytes in such patients to investigate their clinical significance. CD4(+) T lymphocytes were isolated from the peripheral blood of 61 patients with a VL maintained at less than 50 copies/ml for at least 4 months by ART and total DNA was purified. HIV-1 DNA was quantified by nested PCR to calculate the copy number per 1 million CD4(+) lymphocytes (relative amount) and the copy number in 1 ml of blood (absolute amount). For statistical analysis, the Spearman rank or Wilcoxon signed-rank test was used, with a significance level of 5%. CD4 cell counts at the time of sampling negatively correlated with the relative amount of HIV-1 DNA (median = 33 copies/million CD4(+) lymphocytes; interquartile range [IQR] = 7-123 copies/million CD4(+) lymphocytes), but were not correlated with the absolute amounts (median = 17 copies/ml; IQR = 5-67 copies/ml). Both absolute and relative amounts of HIV-1 DNA were significantly lower in six patients in whom ART was initiated before positive seroconversion than in 55 patients in whom ART was initiated in the chronic phase, as shown by Western blotting. CD4 cell counts before ART introduction were also negatively correlated with both the relative and absolute amounts of HIV-1 DNA. Only the relative amounts of HIV-1 DNA negatively correlated with the duration of VL maintenance below the detection limit, while the absolute amounts were not significantly correlated with this period. The amounts of cellular HIV-1 DNA in patients with VLs maintained below the detection limit by the introduction of ART correlated with the timing of ART initiation but not with the duration of ART. In addition, CD4(+) T lymphocytes, which were newly generated by ART, diluted latently infected cells, indicating that measurements of the relative amounts of cellular HIV-1 DNA might be underestimated.


The generation of the oxidized form of creatine kinase is a negative regulation on muscle creatine kinase.
Muscle creatine kinase (CK) is a crucial enzyme in energy metabolism, and it exists in two forms, the reduced form (R-CK) and the oxidized form (O-CK). In contrast with R-CK, O-CK contained an intrachain disulfide bond in each subunit. Here we explored the properties of O-CK and its regulatory role on muscle CK. The intrachain disulfide bond in O-CK was demonstrated to be formed between Cys(74) and Cys(146) by site-directed mutagenesis. Biophysical analysis indicated that O-CK showed decreased catalytic activity and that it might be structurally unstable. Further assays through guanidine hydrochloride denaturation and proteolysis by trypsin and protease K revealed that the tertiary structure of O-CK was more easily disturbed than that of R-CK. Surprisingly, O-CK, unlike R-CK, cannot interact with the M-line protein myomesin through biosensor assay, indicating that O-CK might have no role in muscle contraction. Through in vitro ubiquitination assay, CK was demonstrated to be a specific substrate of muscle ring finger protein 1 (MURF-1). O-CK can be rapidly ubiquitinated by MURF-1, while R-CK can hardly be ubiquitinated, implying that CK might be degraded by the ATP-ubiquitin-proteasome pathway through the generation of O-CK. The results above were further confirmed by molecular modeling of the structure of O-CK. Therefore, it can be concluded that the generation of O-CK was a negative regulation of R-CK and that O-CK might play essential roles in the molecular turnover of MM-CK.


Conformational states in denaturants of cytochrome c and horseradish peroxidases examined by fluorescence and circular dichroism.
Steady-state fluorescence and circular dichroism (CD) were used to examine the unfolding in denaturants of recombinant cytochrome c peroxidase [CCP(MI)] and horseradish peroxidase (HRP) in their ferric forms. CCP(MI) unfolds in urea and in guanidine hydrochloride (GdHCl) at pH 7.0, while HRP loses its secondary structure only in the presence of GdHCl. CCP(MI) unfolds in urea by two distinct steps as monitored by fluorescence, but the loss of its secondary structure as monitored by UV/CD occurs in a single step between 3.4 and 5 M urea and 1.5 and 2.5 M GdHCl. The localized changes detected by fluorescence involve the CCP(MI) heme cavity since the Soret maximum red-shifts from 408 to 416 nm, and the heme CD changes examined in urea are biphasic. The polypeptide of HRP also loses secondary structure in a single step between 1.2 and 2.7 M GdHCl as monitored by UV/CD, and a fluorescence-monitored transition involving conformational change in the Trp117-containing loop occurs above 4 M GdHCl. Free energies of denaturation extrapolated to 0 M denaturant (delta Gd,aq) of approximately 6 and approximately 4 kcal/mol were calculated for CCP(MI) and HRP, respectively, from the UV/CD data. The refolding mechanisms of the two peroxidases differ since heme capture in CCP(MI) is synchronous with refolding while apoHRP captures heme after refolding. Thus, the denatured form of apoHRP does not recognize heme and has to correctly refold prior to heme capture. The half-life for unfolding of native HRP in 6 M GdHCl is slow (519 s) compared to that for CCP(MI) (14.3 s), indicating that HRP is kinetically much more stable than CCP(MI). Treatment with EDTA and DTT greatly destabilizes HRP, and unfolding in 4 M GdHCl occurs with t1/2 = 0.42 s.


Validation of the RT3 accelerometer for measuring physical activity of children in simulated free-living conditions.
This is a validation study of the RT3 accelerometer for measuring physical activities of children in simulated free-living conditions. Twenty-five children age 12-14 years completed indoor testing, and 18 of them completed outdoor testing. Activity counts from the RT3 accelerometer estimated activity energy expenditure (AEE) and the Cosmed K4b2 analyzer measured oxygen uptake. Correlations were found between activity counts and metabolic cost (r = .95, p < .001), metabolic cost and RT3 estimated AEE (r = .96, p < .001) in the indoor test, activity counts and RT3 estimated AEE (r = .97, p < .001) in the outdoor test, and activity counts and metabolic cost when all activities were combined (r = .77, p < .001). Results indicate that the RT3 accelerometer might be used to provide acceptable estimates of free-living physical activity in children.


Colonic nitrite and immunoglobulin G concentrations in dogs with inflammatory bowel disease.
To evaluate lavage analytes as markers of mucosal inflammation in healthy dogs and dogs with inflammatory bowel disease (IBD). Case control study. 9 healthy dogs and 10 dogs with IBD. A polyethylene glycol electrolyte solution was administered into the dogs colons via a rectal balloon catheter prior to colonoscopy. Lavage solution was allowed to remain intraluminally for 30 minutes and then was withdrawn. Lavage supernatant samples were immediately analyzed for total protein, IgG, and nitrite concentrations and myeloperoxidase activity. Mucosal biopsy specimens were obtained from the descending colon and histologically reviewed. All dogs with IBD had mild to severe lymphocytic-plasmacytic colitis, whereas 8 of 9 healthy dogs did not have substantial mucosal inflammation. Myeloperoxidase activity was not detected in lavage samples from healthy dogs or dogs with IBD. Total protein concentration was not significantly different between groups. Mean nitrite and IgG concentrations were significantly higher in samples from dogs with IBD (1.83 nmol/ml and 46 mg/dl, respectively), compared with samples from healthy dogs (0.245 nmol/ml and undetectable concentrations, respectively). Severity of lesions was not correlated with nitrite or IgG concentration. Assay of nitrite and IgG concentrations in colonic lavage fluid is a simple, objective means of evaluating mucosal inflammation in dogs with IBD. Potential uses include monitoring response to treatment and evaluation of complex cases of chronic intestinal inflammation.


Differential effects of nutritive and non-nutritive sweet mouth rinsing on appetite in adults with obesity.
Excessive added sugar intake has been associated with obesity; however, the effect of dietary sweetness on energy intake (EI) and appetite in adults with and without obesity has not yet been determined. To assess the effect of mouth rinses with and without energy and sweetness on measures of appetite, and to compare responses between subjects with body mass index (BMI) between 18.5 and 24.9 kg/m2 or ≥30 kg/m2. In this randomized, double-blind crossover study, 39 subjects (age 23±5y; 17 male, 22 female; BMI 18.5-24.9 kg/m2: n = 21; ≥30 kg/m2: n = 18) performed modified sham-feeding (MSF) with a mouth rinse containing either sucrose, sucralose, maltodextrin, or water for 2min before expectorating the solution. Blood sampling and subjective appetite assessments occurred at baseline (-5) and 15, 30, 60, and 90min post-MSF. After, EI was assessed at a buffet meal and post-meal appetite ratings were assessed hourly for 3h. Post-MSF ghrelin increased for water vs. maltodextrin (water: p = 0.03). Post-MSF cholecystokinin increased following maltodextrin-MSF (p = 0.03) and sucralose-MSF (p = 0.005) vs. sucrose for those with BMI:18.5-24.9 kg/m2 only. There was greater post-MSF desire to eat in response to water vs. sucrose (p = 0.03) and reduced fullness with sucralose for those with BMI≥30 vs. 18.5-24.9 kg/m2 (p < 0.001). There was no difference in EI at the buffet meal by mouth rinse (p = 0.98) or by BMI (p = 0.12). However, there was greater post-meal fullness following sucralose-MSF vs. water (p = 0.03) and sucrose (p = 0.004) for those with BMI≥30 vs. 18.5-24.9 kg/m2. Sucralose rinsing led to greater cephalic phase CCK release in adults with a BMI:18.5-24.9 kg/m2 only; however, ghrelin responses to unsweetened rinses were energy-specific for all adults. As subsequent EI was unaffected, further investigation of cephalic phase appetite is warranted.


An ICEBs1-like element may be associated with the extreme radiation and desiccation resistance of Bacillus pumilus SAFR-032 spores.
Comparisons of the genomes of Bacillus pumilus SAFR-032 and the closely related type strain, B. pumilus ATCC7061(T), exposed an extended region of non-homologous genes. A detailed examination of this region revealed the presence of an ICEBs1-like integrative conjugative element in SAFR-032. A similar element was subsequently located elsewhere in the ATCC7061(T) genome. A detailed comparison of these elements and the ICEBs1 of B. subtilis revealed extremely rapid flux in gene content, genome organization and sequence similarity. It is not clear if the B. pumilus elements as they are currently structured are functional. However, it is clear that the past involvement of these elements has brought multiple genes of unknown function to the SAFR-032 genome and these genes may be responsible for the rapid evolution that led to the extreme radiation and desiccation resistance of this organism's spores.


Effects of carbohydrate availability on lipogenesis in sheep.
1. Lipogenesis in sheep liver and adipose tissue was investigated by incorporation studies in vitro with radioactive glucose and acetate and by assays of key enzymes. 2. Carbohydrate availability to sheep was increased by feeding on a diet containing 70% soluble carbohydrate, by infusing glucose into the abomasum or by direct intravenous infusion of glucose. 3. Under these conditions lipogenesis from glucose and acetate was increased from very low values in lìver and adipose tissue, especially in those animals where rumen fermentation was by-passed by glucose infusion. 4. Large increases in the activities of ATP citrate lyase (EC 220.127.116.11) and NADP-malate dehydrogenase (EC 188.8.131.52) occurred in both tissues when lipogenesis was increased. 5. No adaptations were found in the activities of pyruvate carboxylase (EC 126.96.36.199) in adipose tissue, glucokinase (EC 18.104.22.168) in liver or 3-hydroxybutyrate dehydrogenase (EC 126.96.36.199) in liver. It is proposed that the absence of these enzymes is not related to glucose availability. 6. The effect of glucose on liver lipogenesis was to increase conversion of acetate into lipid. 7. This effect also occurred in adipose tissue, but in this tissue glucose also became a quantitatively important precursor of triglyceride fatty acid.


[The search of small molecules with antipsychotic activity on the background of neurotensin].
Tridecapeptide neurotensin (NT) is known to exert the neuroleptic-like effects in case of its intracerebral administration. The group of systemically active dipeptides , acylprolyltyrosines, was constructed on the background of NT. Methyl ester of N-caproyl-L-prolyl-L-tyrosine (Dilept) was chosen for further development. The paper is dealing with main principles of Dilept'design and with analysis of the experimental data concerning its effect on the "translational" model of schizophrenia--the deficit of prepulse inhibition of the acoustic startle-reaction caused by either dopamine-mimetic, apomorphine, or by the uncompetitive NMDA-blocker, ketamine. Dilept was shown to attenuate these deficits both in case ofintraperitoneal and peroral administration. Dilept is considered as a potential antipsychotic.


Mouthpart deformities and nucleolus activity in field-collected Chironomus riparius larvae.
Chironomid mouthpart deformities and aberrations of their polytenic chromosomes are sublethal responses to toxic stress. These endpoints have been used in several cases as bioindications for sediment pollution. In the present study we aimed to establish whether there was an association between mouthpart deformities and nucleolus activity in the polytenic chromosomes. Such information could be useful to gain insight into the mechanisms involved in the occurrence of mouthpart deformities and their consequences on the larvae. Third-instar larvae of Chironomus riparius were collected at a site downstream of a sewage treatment plant mostly contaminated by pesticides. Larvae were then raised in the laboratory in aquaria containing sediment and water from the study location. During a 16-day period, larvae ready to molt to the fourth instar were reared individually. Within a few hours of their molt, the larvae were preserved. The presence of mouthpart deformities (mentum, mandibles, and pecten epipharyngis) and the percentage of active nucleoli were assessed. Those larvae presenting mentum deformities had a significantly higher incidence of active nucleoli in their polytenic chromosomes than nondeformed larvae. Because a high number of active nucleoli generally indicates increased rRNA synthesis, deformed larvae seemed to exhibit a higher protein synthesis than normal individuals. The synthesis of additional proteins may increase deformed larva tolerance to toxicants.