Decreased B lymphocytes subpopulations are associated with higher atherosclerotic risk in elderly patients with moderate-to-severe chronic kidney diseases.
Cardiovascular diseases (CVD) are the leading cause of death in patients with chronic kidney disease (CKD), and the risk of CVD increases with reductions in renal function. This study aims to investigate the potential roles of B lymphocyte populations in subclinical atherosclerosis (measured by intima-media thickness, IMT) and prognosis in elderly patients with moderate-to-severe CKD. In this study, a total of 219 patients (143 moderate-to-severe CKD patients with stage 3-4 and 76 non-CKD controls) were recruited. B cell subsets: CD19(+)CD5(+) and CD19(+)CD5(-) B cells were analyzed by flow cytometry. Intima-media thickness (IMT) was measured by ultrasound. Correlations between the B cell subsets with IMT and clinical outcome was analyzed. CKD patients showed increased IMT (P = 0.006). The level of CD19(+)CD5(+) and CD19(+)CD5(-) B cells were decreased in CKD patients. Correlation analysis showed that IMT was positively correlated with systolic blood pressure, protein/creatinine ratio and diabetes (P < 0.05), and were negatively correlated with CD19(+)CD5(+) and CD19(+)CD5(-) B lymphocytes (P < 0.05). Stepwise multiple regression analysis showed that CD19(+)CD5(-) B cells had a significant independent association with IMT (P < 0.05). IMT was increased in lower level of total CD19(+) B cells (≤ 0.06 × 109 /L) and CD19(+)CD5(-) B cells (≤ 0.05 × 109 /L) (P < 0.05). Kaplan-Meier analysis showed that patients with lower levels of CD19(+)CD5(+) and CD19(+)CD5(-) B cells exhibited worse survival (P < 0.05). Cox regression analysis showed that patients with lower CD19(+)CD5(+) and CD19(+)CD5(-) B cells counts have a higher risk of all-cause mortality (P < 0.05). Our results showed that decreased CD19(+)CD5(+) and CD19(+)CD5(-) B lymphocytes were correlated with atherosclerosis and worse survival, which indicates that B lymphocytes might involve in atherosclerosis and associated the prognosis of elderly patients with moderate-to-severe CKD.


Cellular fatty acid uptake is acutely regulated by membrane-associated fatty acid-binding proteins.
Cellular long-chain fatty acid uptake is believed to occur largely by protein-mediated transmembrane transport of fatty acids, and also by passive diffusional uptake. It is postulated that the membrane proteins function in trapping of fatty acids from extracellular sources, whereafter their transmembrane translocation occurs by passive diffusion through the lipid bilayer. The key membrane-associated proteins involved are plasma membrane fatty acid-binding protein (FABP(pm)) and fatty acid translocase (FAT/CD36). Their plasma membrane contents are positively correlated with rates of fatty acid uptake. In studies with heart and skeletal muscle we observed that FAT/CD36 is regulated acutely, in that both contraction and insulin can translocate FAT/CD36 from an intracellular depot to the sarcolemma, thereby increasing the rate of fatty acid uptake. In addition, from studies with obese Zucker rats, an established rodent model of obesity and insulin resistance, evidence has been obtained that in heart, muscle and adipose tissue FAT/CD36 is permanently relocated from an intracellular pool to the plasma membrane, resulting in increased fatty acid uptake rates in this condition. These combined observations indicate that protein-mediated fatty acid uptake is a key step in cellular fatty acid utilization, and suggest that malfunctioning of the uptake process could be a critical factor in the pathogenesis of insulin resistance.


Energetics of Walking With a Robotic Knee Exoskeleton.
The authors tested 4 young healthy subjects walking with a powered knee exoskeleton to determine if it could reduce the metabolic cost of locomotion. Subjects walked with a backpack loaded and unloaded, on a treadmill with inclinations of 0° and 15°, and outdoors with varied natural terrain. Participants walked at a self-selected speed (average 1.0 m/s) for all conditions, except incline treadmill walking (average 0.5 m/s). The authors hypothesized that the knee exoskeleton would reduce the metabolic cost of walking uphill and with a load compared with walking without the exoskeleton. The knee exoskeleton reduced metabolic cost by 4.2% in the 15° incline with the backpack load. All other conditions had an increase in metabolic cost when using the knee exoskeleton compared with not using the exoskeleton. There was more variation in metabolic cost over the outdoor walking course with the knee exoskeleton than without it. Our findings indicate that powered assistance at the knee is more likely to decrease the metabolic cost of walking in uphill conditions and during loaded walking rather than in level conditions without a backpack load. Differences in positive mechanical work demand at the knee for varying conditions may explain the differences in metabolic benefit from the exoskeleton.


Occurrence of intra-ventricular hemorrhage among preterm infants admitted in Tikur Anbessa Hospital.
All preterm babies admitted to the neonatal unit of Tikur Anbessa Hospital (TAH) Addis Ababa from November 2000 to November 2001 were followed until discharge or death. There were 298 babies with birth weight of less than 2000 gm and Gestational age of less than 36 weeks. 56 babies died (56/298 = 28%) and consent was obtained to perform autopsy examination on all of them. The mean Gestational age was 31 weeks with the range of 26-35 and the mean birth weight was 1377 grams with the range of 780-1900 grams. Intra ventricular Hemorrhage (IVH) was seen in 18 (18/56 = 32%) preterm infants on autopsy examination. IVH occurred on 36.4% of cases in preterm infants with birth weight of <1500 gm and gestational age of <32 weeks. 16/18 (88.8%) of babies who had IVH were less than 1500 grams. All babies with IVH were in respiratory distress and required resuscitation. Recommendations are made to improve delivery services and neonatal intensive care unit services to reduce incidence of IVH in preterm babies.


Effects of Process Variables on Properties of CoFe2O4 Nanoparticles Prepared by Solvothermal Process.
Controlling the morphology and magnetic properties of CoFe2O4 nanoparticles is crucial for the synthesis of compatible materials for different applications. CoFe2O4 nanoparticles were synthesized by a solvothermal method using cobalt nitrate, iron nitrate as precursors, and oleic acid as a surfactant. The formation of CoFe2O4 nanoparticles was systematically observed by adjusting synthesis process conditions including reaction temperature, reaction time, and oleic acid concentration. Nearly spherical, monodispersed CoFe2O4 nanoparticles were formed by changing the reaction time and reaction temperature. The oleic acid-coated CoFe2O4 nanoparticles inhibited the growth of particle size after 1 h and, therefore, the particle size of CoFe2O4 nanoparticles did not change significantly as the reaction time increased. Both without and with low oleic acid concentration, the large-sized cubic CoFe2O4 nanoparticles showing ferromagnetic behavior were synthesized, while the small-sized CoFe2O4 nanoparticles with superparamagnetic properties were obtained for the oleic acid concentration higher than 0.1 M. This study will become a basis for further research in the future to prepare the high-functional CoFe2O4 magnetic nanoparticles by a solvothermal process, which can be applied to bio-separation, biosensors, drug delivery, magnetic hyperthermia, etc.


Effect of perinatal hypoxia on cardiac tolerance to acute ischaemia in adult male and female rats.
1. The number of adult patients undergoing surgery for congenital cyanotic defects in childhood has increased significantly. Therefore, the aim of the present study was to examine the effect of perinatal hypoxia on the tolerance of the adult myocardium to acute ischaemia-reperfusion injury. 2. Pregnant Wistar rats were exposed to intermittent hypobaric hypoxia 7 days before delivery; pups were born under normoxic conditions and exposed to hypoxia again for 10 postnatal days. After the last hypoxic exposure, all animals were kept for an additional 3 months under normoxic conditions. All experiments were performed on 90-day-old rats. 3. Ventricular arrhythmias were assessed on isolated perfused hearts during 30 min occlusion of the left anterior descending coronary artery. Infarct size was measured on isolated hearts (40 min regional ischaemia and 120 min reperfusion) and on open-chest animals (20 min regional ischaemia and 3 h reperfusion). 4. Perinatal exposure to hypoxia significantly increased cardiac tolerance to ischaemic injury in adult females, as evidenced by the lower incidence and severity of ischaemic ventricular arrhythmias, compared with the normoxic group. The effect of perinatal hypoxia on ischaemic arrhythmias in males was quite the opposite. Myocardial infarct size measured in open-chest animals only was significantly smaller in normoxic females compared with normoxic males. Perinatal exposure to hypoxia had no effect on infarct size in either setting or sex. 5. The results of the present study support the hypothesis that perinatal hypoxia is a primary programming stimulus in the heart that may lead to sex-dependent changes in cardiac tolerance to acute ischaemia in later adult life. This would have important implications for patients who have experienced prolonged hypoxaemia in early life.


Does transfer of work from a public sector organisation to a commercial enterprise without staff reductions increase risk of long-term sickness absence among the staff? A cohort study of laboratory and radiology employees.
Privatisations of public sector organisations are not uncommon, and some studies suggest that such organisational changes may adversely affect employee health. In this study, we examined whether transfer of work from public sector hospital units to commercial enterprises, without major staff reductions, was associated with an increased risk of long-term sickness absence among employees. A cohort study of 962 employees from four public hospital laboratory and radiology units in three hospitals which were privatised during the follow-up and 1832 employees from similar units without such organisational changes. Records of new long-term sick leaves (>90 days) were obtained from national health registers and were linked to the data. Mean follow-up was 9.2 years. Age- and sex-adjusted HR for long-term sickness absence after privatisation was 0.83 (95% CI 0.68 to 1.00) among employees whose work unit underwent a change from a public organisation to a commercial enterprise compared with employees in unchanged work units. Further adjustments for occupation, socioeconomic status, type of job contract, size of residence and sick leaves before privatisation had little impact on the observed association. A sensitivity analysis with harmonised occupations across the two groups replicated the finding (multivariable adjusted HR 0.92 (0.70-1.20)). In this study, transfer of work from public organisation to commercial enterprise did not increase the risk of long-term sickness absence among employees.


Facile Synthesis of Carbon- and Nitrogen-Doped Iron Borate as a Highly Efficient Single-Component Heterogeneous Photo-Fenton Catalyst under Simulated Solar Irradiation.
The development of a heterogeneous catalyst for use in environmental remediation remains a challenging and attractive research endeavor. Specifically, for Fenton reactions, most research approaches have focused on the preparation of iron-containing heterostructures as photo-Fenton catalysts that utilize visible light for enhancing the degradation efficiency. Herein, the synthesis and novel application of C,N-doped iron borates are demonstrated as single-component heterogeneous photo-Fenton catalysts with high Fenton activity under visible light. Under the optimal conditions, 10 mg of the catalyst is shown to achieve effective degradation of 10 ppm methylene blue (MB) dye, Rhodamine B (RhB) dye, and tetracycline (TC) under simulated solar irradiation with a first-order rate constant of k = 0.218 min-1, 0.177 min-1, and 0.116 min-1, respectively. Using MB as a model system, the C,N-doped iron borate exhibits 10- and 26-fold increases in catalytic activity relative to that of the 50 nm hematite nanoparticles and that of the non-doped iron borate, respectively, in the presence of H2O2 under the simulated solar irradiation. Furthermore, the optimum reaction conditions used only 320 equivalents of H2O2 with respect to the concentration of dye, rather than the several thousand equivalents of H2O2 used in conventional heterogeneous Fenton catalysts. In addition, the as-prepared C,N-doped iron borate achieves 75% MB degradation after 20 min in the dark, thus enabling the continuous degradation of pollutants at night and in areas with poor light exposure. The stability and recyclability of C,N-doped iron borate for the oxidation of MB was demonstrated over three cycles with insignificant loss in photo-Fenton activity. The high Fenton activity of the C,N-doped iron borate is considered to be due to the synergistic action between the negatively-charged borate ligands and the metal center in promoting the Fenton reaction. Moreover, carbon and nitrogen doping are shown to be critical in modifying the electronic structure and increasing the conductivity of the catalyst. In view of its synthetic simplicity, high efficiency, low cost of reagents, and minimal cost of operation (driven by natural sunlight), the as-prepared heterogeneous single-component metal borate catalyst has potential application in the industrial treatment of wastewater.


Efficacy and safety of lacidipine, a new long-lasting calcium antagonist, in elderly hypertensive patients.
Elderly patients are becoming a greater proportion of the hypertensive population. In addition, they may respond differently to drugs, both pharmacodynamically and pharmacokinetically. Therefore, approximately 25% of the patients treated with lacidipine in early studies were over 65 years old. In three double-blind, parallel-group comparative trials, 118 elderly hypertensive patients were treated with lacidipine or comparators, either atenolol, nifedipine SR, or hydrochlorothiazide (HCTZ). Lacidipine was at least as effective in lowering blood pressure as the comparators, as well tolerated as nifedipine SR (but with a significantly lower incidence of edema) and HCTZ, and better tolerated than atenolol. In a double-blind, placebo-controlled, parallel-group, dose-response study of 131 elderly hypertensive patients randomized to receive either lacidipine or placebo, lacidipine significantly reduced the diastolic blood pressure compared with placebo. In the long-term evaluation, more patients required titration with 2 mg of lacidipine than with 4 mg. These results suggest that 4 mg once daily is an effective and well-tolerated antihypertensive treatment in the elderly and, as with the general adult population, represents the optimal long-term maintenance dose.


HPTLC-densitometric method of determination of oleanolic acid in the Lamii albi flos.
HPTLC combined with densitometric method was used to determine the content of oleanolic acid in acetone extract from the Lamii albi flos L. The plant extract was separated on Si 60 HPTLC plates and determined with the use of two densitometric methods: measurement of fluorescence and absorbance. The content of oleanolic acid was statistically calculated. In a measurement of absorbance in 1 g of the dry Lamii albi flos L. 1458 microg of oleanolic acid was determined (0.147%). In a fluorescence method in 1 g of the plant material 1516 microg of oleanolic acid was determined (0.149%).


Thymomas in rabbits: clinical evaluation, diagnosis, and treatment.
Thymomas are rarely recorded in rabbits, and the literature includes comparatively few cases. Medical records were reviewed to identify all pet rabbits in which a mediastinal mass was diagnosed between Feb 2007 and Jan 2010. Signalment, history, clinical signs, diagnostic work-up (including laboratory data, diagnostic imaging, and ultrasound-guided fine-needle aspiration of the mediastinal mass), treatment modalities, survival time, and histologic findings were evaluated. Cytologic and/or histopathologic examinations revealed thymomas in all rabbits with mediastinal masses (n=13). Rabbits with thymomas showed clinical signs of dyspnea (76.9%), exercise intolerance (53.9%), and bilateral exophthalmos (46.2%). In seven rabbits the thymoma was removed surgically. Two rabbits were treated conservatively, and four rabbits were euthanized because of their poor clinical condition. The two rabbits that underwent surgery were euthanized 6 mo and 34 mo later. Mediastinal masses in rabbits appear to be more common than previously believed and consist primarily of thymomas rather than thymic lymphomas. Cytology of samples collected by ultrasound-guided fine-needle aspiration is an accurate diagnostic tool for the identification of thymomas in rabbits. Due to a high rate of perioperative mortality, intensive perioperative care and the provision of a low-stress environment are recommended for a successful thoracotomy.


Differential induction of helper and killer T cells from isolated CD4+CD8+ thymocytes in suspension culture.
Thymocytes of T cell receptor transgenic mice with nonselecting and RAG-2 -/- backgrounds were developmentally arrested at the CD4+CD8+ stage before positive selection. These thymocytes underwent lineage commitment upon transient stimulation with a combination of ionomycin, a calcium ionophore, and phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, in suspension culture. The effective drug doses were limited within narrow ranges and much lower than those which induce proliferation of mature T cells. The doses corresponded to those which inhibit glucocorticoid-induced apoptosis in these thymocytes. CD4 lineage commitment required longer duration, higher intensity of the stimulation, or both, than CD8 lineage commitment. Functional helper T cells (Th1 and Th2) were induced from the CD4 lineage-committed cells upon secondary stimulation with a combination of ionomycin and PMA followed by lymphokine treatment. Cytotoxic T cells were induced from the CD8 lineage-committed cells upon incubation with concanavalin A and irradiated splenic dendritic cells, but not with the combination of ionomycin and PMA. These results indicate that positive selection is mimicked by the pharmacological stimulation in the absence of other cell types, but that final maturation of CD8 T cells may require a different signal.


Group psychotherapy for persons with multiple personality and dissociative disorders.
Group psychotherapy is a valuable part of the treatment of patients with multiple personality and dissociative disorders. After reviewing the sparse literature on the subject, the author describes the use of group psychotherapy with these patients alone, as well as with two types of groups in which these patients may participate: incest survivors and general group therapy patients. She concludes by emphasizing the need for expert training for therapists who conduct group psychotherapy with multiple personality and dissociative disorder patients.


Hierarchical MOF-on-MOF Architecture for pH/GSH-Controlled Drug Delivery and Fe-Based Chemodynamic Therapy.
Chemotherapy is still an important and effective clinical treatment for cancer. However, individual drugs hardly achieve precise controlled release and targeted therapy, thus resulting in unavoidable side effects. Fortunately, the emergence of drug carriers is expected to solve the above problems. In this work, the MOF-on-MOF strategy was adopted to encapsulate DOX into double-layer NH2-MIL-88B to fabricate a core-shell-structured DOX@NH2-MIL-88B-On-NH2-MIL-88B (DMM) and then realize the pH and GSH dual-responsive controlled DOX release. Because of the core-shell structure, the drug-loading capacity of DMM reached 14.4 wt %, which was nearly twice that of DOX@NH2-MIL-88B (DM), and the controlled release performance of DMM was also improved at the same time, greatly improving the kinetics equilibrium time of DOX from 2 h (DM) to 16 h (DMM) at pH 5.0. Moreover, we found that DMM also possessed peroxidase-like catalytic activity under acidic conditions, which could catalyze H2O2 to produce •OH, exhibiting the potential chemodynamical treatment of cancer. Cell experiments showed that DMM had a significant inhibitory effect against 4T1 cancer cells, and the survival rate of 4T1 cells was less than 20% at 100 ppm.


Fatigue of zirconia and dental bridge geometry: Design implications.
Zirconia is currently used as a framework material for posterior all-ceramic bridges. While the majority of research efforts have focused on the microstructure and corresponding mechanical properties of this material, clinical fractures appear to be largely associated with the appliance geometry. The objective of this study was to estimate the maximum stress concentration posed by the connector geometry and to provide adjusted estimates of the minimum connector diameter that is required for achieving 20 years of function. A simple quantitative description of the connector geometry in an all-ceramic 4-unit bridge design is used with published stress concentration factor charts to estimate the degree of stress concentration and the maximum stress. The magnitude of stress concentration estimated for clinically relevant connector geometries ranges from 2 to 3. Using previously published recommendations for connector designs, adjusted estimates for the minimum connector diameter required to achieve 20 years of clinical function are presented. To prevent clinical fractures the minimum connector diameter in multi-unit bridges designs must account for the loads incurred during function and the extent of stress concentration posed by the connector geometry.


9-methyl-7-bromoeudistomin D, a powerful radio-labelable Ca++ releaser having caffeine-like properties, acts on Ca(++)-induced Ca++ release channels of sarcoplasmic reticulum.
9-Methyl-7-bromoeudistomin D (MBED), a derivative of eudistomin D isolated from a marine tunicate, induced Ca++ release from the heavy fraction of fragmented sarcoplasmic reticulum (HSR) in the same way as that of caffeine, followed by spontaneous Ca++ reuptake in the Ca++ electrode experiment. The rate of 45Ca++ efflux from HSR vesicles was accelerated markedly by MBED or caffeine in a concentration-dependent manner. The 50% effective concentrations of MBED and caffeine were approximately 1 microM and 1 mM, respectively, indicating that MBED is 1000 times more potent than caffeine in HSR. Procaine, ruthenium red or Mg++ caused concentration-dependent inhibition of MBED-triggered Ca++ release from HSR. The bell-shaped profile of Ca++ dependence for MBED is very similar to that of caffeine. The caffeine-produced maximum response of 45Ca++ efflux was increased further by adenosine-5'-(beta, gamma-methyl-ene)triphosphate, whereas that was not changed by MBED. MBED also caused Ca++ release from sarcoplasmic reticulum (SR) of chemically skinned fibers. These stimulatory effects of MBED on the Ca++ release from skeletal muscle SR were almost indistinguishable from those of caffeine except the difference in potencies. The [3H]ryanodine binding to junctional terminal cisternae membranes was not inhibited by MBED or caffeine. MBED did not cause Ca++ release from the light fraction of fragmented SR and turbidity change of mitochondrial suspension. These observations suggest a most likely idea that MBED binds to the caffeine-binding site in the Ca channel protein and thus produces the potentiation of Ca(++)-induced Ca++ release from SR.(ABSTRACT TRUNCATED AT 250 WORDS)


The puh structural gene coding for the H subunit of the Rhodospirillum rubrum photoreaction center.
The Rhodospirillum rubrum structural gene puh, coding for the photoreaction center H polypeptide, and three other putative genes that surround puh were cloned and sequenced. The deduced 257 amino acid H polypeptide has a molecular weight of 27,909, in close agreement with polyacrylamide gel electrophoresis determination. Hydropathy plots predict a single hydrophobic alpha helix. The H polypeptide of Rhodospirillum rubrum shares only 23% of its residues with all three of the H polypeptides from Rhodopseudomonas viridis, Rhodobacter capsulatus, and Rhodobacter sphaeroides. Despite this apparent low degree of similarity, statistical analysis leaves no doubt about their close relatedness. Interspecies evolutionary distance, assessed by this analysis, confirms the closeness of the two Rhodobacter species, Rhodospirillum rubrum and Rhodopseudomonas viridis being approximately equidistant from them. Three regions of the H polypeptide are highly conserved in all four species. They correspond to known contact points of H with the complex of the other two (L and M) subunits on the cytoplasmic side of the membrane. A glutamic acid residue (H polypeptide residue 177), conserved in the other bacteria and suggested to be involved in the binding of secondary quinone QB, is replaced by serine in Rhodospirillum rubrum. The open reading frames G115, I2372, and I3087 are predicted to, respectively, encode polypeptides of 480, 224, and 155 residues coiled in 10, 2, and 1 transmembrane helices. Open reading frame G115 shares 56% identical residues with F1696, a sequence arranged in the genome of Rhodobacter capsulatus. The gene product of ORF I3087 is predicted to share highly similar sequences with nitrogenase reductase (encoded by nifH) of 11 different bacterial species and is suggested to have a regulatory function.


Evaluation of new cases of HCV infection in thalassaemia patients for source of infection.
Screening tests on blood bags is important step for blood safety. In Iran, screening for HCV started from 1996. We decided to determine the new cases of hepatitis C in our thalassemic patients, after screening of blood bags was initiated and trace backing from recipients to find their donors. The study was done on patients with complete files for HCVAb test results. Only cases that had a positive HCVAb result following a negative result were considered as new cases. For trace backing, we recorded the blood transfusions' date and the blood bags' number from last negative test results (HCVAb) to the first positive test result. These data were sent to the transfusion center. The suspected donors were contacted and asked to be tested again in the transfusion center. A total of 395 patients were studied; 229 (58%) males and 166 (42%) females. Mean age was 27.5 years. We had 109 HCV (27.5%) positive cases of whom 21 were infected after 1996. We traced the last five cases contaminated during 2003 and 2004. These five patients had 13, 10, 13, 12, and 6 donors, respectively (totally 54 donors were found). We proved the healthy state in 68.5% (37 of 54) of our donors population. Of them, 81% were repeated donors and 17 of 54 donors (31.5%) could not be traced (because of change in addresses). We did not have any HCV new cases after 2004. We could not prove HCV transmission from donors as the source of infection. Although parenteral transmission is always on top of the list in HCV infection, the possibility of hospital and/or nursing personnel transmission and/or patient-to-patient transmission such as use of common instruments like subcutaneous Desferal(®) infusion pumps; which the patients used for iron chelation therapy, should also be kept in mind.


Cardiac tamponade in rheumatoid arthritis.
A 56-year-old woman with definite rheumatoid arthritis developed cardiac tamponade while her disease was both clinically and serologically inactive. To our knowledge such a complication has been reported only once previously.


Effect of cyclosporine, cyclosporine metabolite 17, and other cyclosporine-related compounds on T lymphocyte clones derived from rejected human kidney grafts. I. Inhibition of proliferation.
The effect of cyclosporine and metabolite 17 (M17) as well as other CsA-related compounds (CsG, dihydro-CsC, dihydro-CsD, CsH, B5.49, and H7.94) was tested on T lymphocyte clone proliferation. In these experiments, antigen and interleukin 2 (IL-2) dependent long-term T lymphocyte clones derived from a rejected human kidney graft infiltrate were used. They were specifically committed (proliferation and cytotoxicity) for the donor Epstein-Barr virus (EBV)-transformed cells. CsA strongly inhibited clone T cell proliferation induced by the antigen. Inhibition of antigen-driven proliferation was reversed by pure recombinant IL-2 (rec-IL-2) only when low amounts of CsA (less than 25 ng/ml) were used, whereas this lymphokine was ineffective at higher but still pharmacological CsA concentrations (50-500 ng/ml). Increasing rec-IL-2 concentrations did not modify this finding. In addition, CsA, did not inhibit the growth signal(s) induced by rec-IL-2/IL-2 receptor interactions when R-IL-2 is pre-expressed on clone cells. M17 was far less effective in inhibiting antigen-induced clone cell proliferation (50% inhibition at 16 ng/ml versus 500 ng/ml with, respectively, CsA and M17) but was nevertheless inhibitory. This observation, if extended to other metabolites, could be important for interpretation of the relevance of "CsA" concentration through radio-immunoassay monitoring of recipients' blood. Although CsA appeared to display the major inhibitory effect, dihydro-CsC and CsG, as well as B5.49 and H7.94 CsA-related compounds, also exhibited strong activity. Dihydro-CsD was less inhibitory, and CsH had no effect.


Atrial Fibrillation With Decompensated Heart Failure Complicated With Non-ST Elevation Myocardial Infarction.
Non-ST-elevation myocardial infarction (NSTEMI) has a less severe ratio of acute coronary syndromes compared with ST-segment elevation myocardial infarction (STEMI), arising from complete occlusion of a major coronary artery. The name implies a syndrome that does not exhibit the dramatic ST-elevation seen in the traditional 12-lead ECG in chest pain patients with a confirmed diagnosis of STEMI. The crucial clinical significance of NSTEMI is that delay in diagnosis can lead to increased morbidity, risk of arrhythmia, and death. It was recently reported that atrial fibrillation (AF) correlates with the risk rise of myocardial infarction (MI), although the mechanism underlying this association is currently unknown. Does atrial fibrillation with decompensated heart failure (DHF) get complicated with NSTEMI? In this article, we describe the case of a 77-year-old male patient diagnosed and admitted as NSTEMI complicated by DHF.


Profiling the secretion of soluble mediators by end stage osteoarthritis synovial tissue explants reveals a reduced responsiveness to an inflammatory trigger.
Evidence is accumulating that synovial tissue plays an active role in osteoarthritis (OA), however, exact understanding of its contribution is lacking. In order to further elucidate its role in the OA process, we aimed to identify the secretion pattern of soluble mediators by synovial tissue and to assess its ability to initiate cartilage degeneration. Synovial tissue explants (STEs) obtained from donors without history of OA (n = 8) or from end stage OA patients (n = 16) were cultured alone or together with bovine cartilage explants in the absence or presence of IL-1α. The secretion of 48 soluble mediators was measured and the effect on glycosaminoglycan (GAG) release and matrix metalloproteinase (MMP) activity was determined. Normal and OA STEs secreted comparable levels of almost all measured soluble mediators. However, in the presence of IL-1α these mediators were less secreted by OA than by normal STEs of which 15 differed significantly (p<0.01). No effect of normal or OA STEs on GAG release from the cartilage explants was observed, and no differences in MMP activity between OA and normal STEs were detected. Unexpectedly, a comparable secretion profile of soluble mediators was found for OA and normal STEs while the reduced responsiveness of OA STEs to an inflammatory trigger indicates a different state of this tissue in OA patients. The effects could be the result of prolonged exposure to an inflammatory environment in OA development. Further understanding of the pro-inflammatory and inflammation resolving mechanisms during disease progression in synovial tissue may provide valuable targets for therapy in the future.


An fMRI Study of the Impact of Block Building and Board Games on Spatial Ability.
Previous studies have found that block play, board games, and puzzles result in better spatial ability. This study focused on examining the differential impact of structured block play and board games on spatial processing. Two groups of 8-year-old children were studied. One group participated in a five session block play training paradigm and the second group had a similar training protocol but played a word/spelling board game. A mental rotation task was assessed before and after training. The mental rotation task was performed during fMRI to observe the neural changes associated with the two play protocols. Only the block play group showed effects of training for both behavioral measures and fMRI measured brain activation. Behaviorally, the block play group showed improvements in both reaction time and accuracy. Additionally, the block play group showed increased involvement of regions that have been linked to spatial working memory and spatial processing after training. The board game group showed non-significant improvements in mental rotation performance, likely related to practice effects, and no training related brain activation differences. While the current study is preliminary, it does suggest that different "spatial" play activities have differential impacts on spatial processing with structured block play but not board games showing a significant impact on mental rotation performance.


DNAJB1/HSP40 Suppresses Melanoma Differentiation-Associated Gene 5-Mitochondrial Antiviral Signaling Protein Function in Conjunction with HSP70.
Melanoma differentiation-associated gene 5 (MDA5) is a pattern recognition receptor that recognizes cytoplasmic viral double-stranded RNA (dsRNA) and initiates rapid innate antiviral responses. MDA5 forms a filament-like multimer along the dsRNA leading to oligomerization, which in turn activates the adaptor protein mitochondrial antiviral signaling protein (MAVS) to provide a signal platform for the induction of type I interferon (IFN) and proinflammatory cytokines. The conformational switch of MDA5 causes antiviral defense, but excessive activation of the MDA5-MAVS pathway may result in autoimmune diseases. The regulatory mechanisms of MDA5 activation remain largely unknown. By yeast 2-hybrid, we identified DNAJB1, a member of the HSP40 (heat shock protein 40) family, as an MDA5-binding protein. HSP40s usually cowork with HSP70s. We found that dsRNA stimulation with physiological conditions upregulated the expression levels of DNAJB1 and HSP70; then the proteins were coupled and translocated into the stress granules, where MDA5 encounters dsRNA. DNAJB1 disrupted MDA5 multimer formation, resulting in the suppression of type I IFN induction. The disruption of endogenous DNAJB1 increased MDA5- and MAVS-mediated IFN promoter activation and rendered cells virus resistant. HSP70 inhibitor also enhanced the IFN-inducing function of MDA5 and MAVS. These results suggest that the DNAJB1-HSP70 complex functions for the natural maintenance of RNA sensing by interacting with MDA5/MAVS.


Antimicrobial activity of MDL 63,246, a new semisynthetic glycopeptide antibiotic.
MDL 63,246 is a semisynthetic derivative of the naturally occurring glycopeptide antibiotic MDL 62,476 (A40926). It was more active in vitro against Staphylococcus aureus and coagulase-negative staphylococci than MDL 62,476, teicoplanin, and vancomycin and was more active than mideplanin (MDL 62,873) against some isolates. MDL 63,246 had excellent activity against streptococci and teicoplanin-susceptible enterococci, and it also had in vitro activity against some VanA enterococcal isolates. It was more active than teicoplanin and vancomycin against acute staphylococcal, streptococcal, and enterococcal septicemia in immunocompetent and neutropenic mice. It was highly efficacious in reducing the bacterial load in the hearts of rats in staphylococcal endocarditis experiments and the bacterial load of Staphylococcus epidermis in a high infection model in neutropenic mice. The excellent in vivo activity of MDL 63,246 appears to correlate both with its in vitro antibacterial activity and with its long half-life in rodents.


Involvement of GPR12 in the induction of neurite outgrowth in PC12 cells.
GPR12, an orphan G protein-coupled receptor, constitutively activates the Gs signaling pathway and further increases intracellular cyclic AMP. GPR12 overexpression has been reported to promote neurite extension in neurons or transform neuro2a neuroblastoma cells into neuron-like cells. However, the possible effects and mechanisms of GPR12 in the differentiation of PC12 cells are still unknown. The present study shows that GPR12 overexpression induced PC12 cells differentiation into neuron-like cells with enlarged cell sizes and neuritogenesis possibly via activation of Erk1/2 signaling and significantly increased the expression of several neurite outgrowth-related genes, including Bcl-xL, Bcl-2 and synaptophysin. These findings indicate that GPR12 may play a role in neurite outgrowth during PC12 cell differentiation.


[ZHANG Wei-hua's experience in clinical treatment of somatalgia with "point-zone-strip stimulation technique" of acupuncture].
The clinical experience in treatment of somatalgia with "point-zone-strip stimulation technique" of acupuncture of professor ZHANG Wei-hua was summarized. Professor ZHANG integrates the theories of the cutaneous region of meridian, biaoben, "taking tender point as acupoint" and local holography as a whole in treatment of somatalgia. The "point-stimulation technique" of acupuncture (subcutaneous needling technique) is adopted for the painful site less than 3 cm in diameter, the "zone-stimulation technique" (surrounding needling technique) is for the site larger than 3 cm in diameter and the "strip-stimulation technique" (cubit-tibia needling technique) is for various acute and chronic somatalgia. These three needling techniques are applicable singly or in combination in clinical practice.


Towards Automated Three-Dimensional Tracking of Nephrons through Stacked Histological Image Sets.
An automated approach for tracking individual nephrons through three-dimensional histological image sets of mouse and rat kidneys is presented. In a previous study, the available images were tracked manually through the image sets in order to explore renal microarchitecture. The purpose of the current research is to reduce the time and effort required to manually trace nephrons by creating an automated, intelligent system as a standard tool for such datasets. The algorithm is robust enough to isolate closely packed nephrons and track their convoluted paths despite a number of nonideal, interfering conditions such as local image distortions, artefacts, and interstitial tissue interference. The system comprises image preprocessing, feature extraction, and a custom graph-based tracking algorithm, which is validated by a rule base and a machine learning algorithm. A study of a selection of automatically tracked nephrons, when compared with manual tracking, yields a 95% tracking accuracy for structures in the cortex, while those in the medulla have lower accuracy due to narrower diameter and higher density. Limited manual intervention is introduced to improve tracking, enabling full nephron paths to be obtained with an average of 17 manual corrections per mouse nephron and 58 manual corrections per rat nephron.


Reversible inhibition of growth of B16 melanoma cells by decreased amino acid nutrition.
The effect of limited amino acid nutrition upon the growth of B16 melanoma cells was investigated. It was observed that the cells in Basal Medium Eagle do not proliferate and are inhibited predominantly in the G1 phase of cell cycle. The cells which were inhibited in growth for 7 or 12 days in Basal Medium Eagle were able to commence proliferation when transferred to Eagle's Minimal Essential Medium containing higher concentration of amino acids. The proliferating cells were found to be more evenly distributed throughout all phases of the cell cycle. The reversible inhibition of growth of B16 melanoma cells was caused by decreased concentrations of amino acids and not by their depletion in the culture medium. The B16 melanoma cells which are known to be capable of highly autonomous growth in the absence of extracellular hormones and growth factors have appeared to be sensitive to nutritional inadequacy.


A comparative study of ectopic production of human chorionic gonadotropin and human chorionic somatotropin by carcinoma of the uterine cervix.
A comparative study was made on the ectopic production of chorionic gonadotropin (hCG) and chorionic somatotropin (hCS) by carcinoma of the uterine cervix. Incidence of hCG in the sera of cancer patients was much higher than hCS. hCS has a better prospect in early detection of cancer cervix than hCG. All hCS-producing tumors and the majority of hCG-producing ones were histologically diagnosed as squamous cell carcinoma. The source of hCG and hCS were found to be the tumor cells. A fall or disappearance of detectable hCG and hCS was noted following surgery or radiotherapy.


Hypotensive effect of a newly identified peptide, proadrenomedullin N-terminal 20 peptide.
Proadrenomedullin N-terminal 20 peptide (PAMP) and adrenomedullin (AM), which are both derived from proadrenomedullin, exhibit marked hypotensive effects. We recently reported that PAMP but not AM reduced the release of norepinephrine from peripheral sympathetic nerve endings. Our present objective was to clarify the involvement of the sympathetic nervous system in the hypotensive action of PAMP and AM. Intravenous administration of PAMP (10, 20, and 50 nmol/kg) to conscious rats induced less reflex tachycardia (5 +/- 5, 10 +/- 5, and 14 +/- 6 beats per minute [bpm]) than that of AM in 0.1, 0.5, and 1.0 nmol/kg doses (5 +/- 8, 20 +/- 7, and 38 +/- 5 bpm, P < .01) although both agents showed similar hypotensive effects. We evaluated the effect of PAMP on blood pressure in pithed rats whose sympathetic nervous systems were abolished. In pithed rats, AM (-2 +/- 1, -7 +/- 1, and -10 +/- 3 mm Hg; NS, P < .05, and P < .01, respectively) but not PAMP evoked hypotension. In contrast, administration of PAMP (-3 +/- 1, -11 +/- 2, and -14 +/- 4 mm Hg; P < .05, P < .01, and P < .01, respectively) as well as adrenomedullin (-2 +/- 2, -10 + 3, and -15 +/- 4 mm Hg; NS, P < .01, and P < .01) significantly reduced blood pressure in electrically stimulated, pithed rats, which had reached almost the same levels as in conscious rats. In electrically stimulated, pithed rats, plasma norepinephrine level was reduced by PAMP but not by vehicle or AM. These findings suggest that the hypotensive effect of PAMP is mainly due to inhibition of peripheral sympathetic nerve activity.


Determination of Steroidal Saponins and Fixed Oil Content in Fenugreek (Trigonella foenum-graecum) Genotypes.
Trigonella foenum-graecum, commonly called fenugreek, is a leguminous plant native to many Asian, Middle Eastern and European countries. Fenugreek oil is very effective in digestion. Identification of fenugreek genotype rich in saponins and fixed oil will be useful for pharmaceutical industries. In the present study, steroidal saponin and fixed oil content was analysed in 46 diverse fenugreek genotypes on dry weight basis. Significant differences were observed in the total saponin and fixed oil content among the genotypes. Saponin and fixed oil content ranged from 0.92 g to 1.68 g and 3.25 to 6.88 g with corresponding mean value of 1.34 g and 5.19 g/100 g dw, respectively.


[Microbial warfare and bioterrorism].
Infectious diseases have been used as warfares since ancient times. Since the 1920s military organizations have studied bacteria of anthrax, plague, tularemia, botulism, brucelloses, glander, Q-fever, and smallpox virus, Filo-, Arena-, Bunyaviruses causing hemorrhagic fever or Alphaviruses eliciting encephalitis. These can be dispersed by aerosol. Salmonellae, Shigellae, Vibrio cholerae, distinguished Escherichia coli strains are suitable to contaminate food, water, pharmaceutical products. Fanatical groups or terrorist individuals deploy microbe weapons. In the future, genetically engineered recombinant microbes could be used with genomes containing multiple resistance elements to antimicrobial compounds and additional virulence factors. These become resistant to all known treatment regimens, vaccination and the host immune response. Microbial terrorist attacks result in an outbrake on a restricted area with large number of casualties. The disease course is severe and unusual followed by high mortality. Identification of microbes is complicated and delayed. Most countries have neither laboratories at high biosafety level nor specially trained personnel. Physicians might misdiagnose these diseases. Health care systems with minimal elasticity face difficulties in maintaining mass quarantine. A considerable part of health care workers leave hospitals. No plan is available to stockpile medicines. Robust surveillance and laboratory systems coordinated at international level must be established. All health care personnel should be trained periodically to gain practical skills. Additional standards governing working conditions with selected microbes will be enforced by law. Related scientific data might be published with restricted access only.


Dihydronicotinamide adenine dinucleotide diaphorase in the central nervous system of the crested newt.
By using a histochemical procedure, the distribution of neurons containing dihydronicotinamide adenine dinucleotide diaphorase (NADPHd) was examined in the brain, retina and olfactory epithelium of the urodele amphibian Triturus carnifex. Positive nerve fibers and terminals were observed throughout the brain and cell bodies were seen within the telencephalon, optic tectum, brain stem, cerebellum and spinal cord. In the retina, NADPHd labeling was localized in the outer segment of photoreceptors and in some amacrine cells as well as in the outer and inner plexiform layers. In the olfactory epithelium, NADPHd labeling was found in the olfactory neurons. By comparing NADPHd distribution with nitric oxide synthase (NOS) immunoreactivity (using a polyclonal antiserum raised against mouse cerebellar NOS) it was found that NADPHd labeling and NOS immunoreaction patterns generally matched. The organization of NADPHd and NOS containing neurons in the central nervous system of the crested newt, which is simpler than in other vertebrates investigated, shows some peculiarities, such as the occurrence of NADPHD in the pinealocytes of the epiphysis, nucleus rubber of the brain stem and eminentia cerebellaris ventralis of the cerebellum.


Human leucocyte elastase and serum alpha 1-antitrypsin.
Human leucocyte elastase concentration and its major circulating inhibitor, the alpha 1-antitrypsin, were compared in blood samples taken from 17 healthy male donors. Leucocyte elastase concentration was linearly correlated to the serum antitrypsin activity determined by its phenotypic constitution. Thus it seems that cellular elastase and its circulating inhibitor activities are closely coregulated. This might be mediated by the leucocyte elastase receptors which internalize free elastase possibly suppressing synthesis of the enzyme.


The complete mitochondrial genome of Solea ovata (Pleuronectiformes: Soleidae).
Solea ovata (Pleuronectiformes: Soleidae) is characterized by eyes on right side and an ovata body with small ctenoid scales on both sides. In this article, the complete mitogenome of Solea ovata was first determined. The total length is 16,782 bp, containing 13 protein-coding genes, 22 tRNA genes, and 2 rRNA genes (12S and 16S), as well as a putative control region and a L-strand replication origin (OL). Except eight tRNA and ND6 genes, all other mitochondrial genes are encoded on the heavy strand. Overall base composition is 29.2% A, 29.4% C, 15.9% G, and 25.5% T with a slight AT bias of 54.7%. The determination of S. ovata complete mitogenome could contribute to understanding the systematic evolution of the genus Solea and further phylogenetic study on Soleidae and Pleuronectiformes.


Analysis of 8-aminonaphthalene-1,3,6-trisulfonic acid labelled N-glycans by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry.
Fluorophore-assisted carbohydrate electrophoresis (FACE) is a fast and efficient analytical method which is now widely used in glycobiology for the separation and quantification of free or glycoprotein-released oligosaccharides. However, since identification by FACE of N-glycan structures is only based on their electrophoretic mobility after labelling with 8-aminonaphthalene-1,3, 6-trisulfonic acid (ANTS), co-migration of derived glycans on gel could occur which may result in erroneous structural assignments. As a consequence, a protocol was developed for the fast and efficient matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometric analysis of ANTS-labelled N-glycans. N-Glycans were isolated from plant and mammalian glycoproteins, reductively aminated with the charged fluorophore 8-aminonaphthalene-1, 3, 6-trisulfonic acid (ANTS) and separated using high resolution polyacrylamide gel electrophoresis. The ANTS-labelled glycans were eluted from FACE gel slices and then analysed by MALDI-TOF mass spectrometry in negative ion mode. Using 3-aminoquinoline containing 2.5 mM citrate NH(4)(+) as matrix, neutral N-linked N-glycans, as well as labelled sialylated oligosaccharides, were found to be easily detected in the 2-10 picomole range giving rise to ¿M - H(-) ions.


Quantification of abnormal upper limb movement during walking in people with acquired brain injury.
Abnormal upper limb movements frequently affect people with acquired brain injury (ABI) during walking. Three-dimensional motion analysis (3DMA) can quantify upper limb abnormality kinematically, with composite scores condensing multiple joint axes data into a single score. Are 3DMA-derived composite scores valid (known-groups and convergent validity), reliable and able to quantify speed-related changes in abnormal upper limb movement during walking? This observational study compared 42 adults with ABI and abnormal upper limb movements during walking with 36 healthy controls (HC) at a matched walking speed intention. Participants underwent 3DMA assessment of self-selected and fast walking speeds. Composite scores quantified the affected upper limb's kinematic abnormality. The Arm Posture Score arithmetic mean version (APSam) and 1.96 standard deviation reference-range scaled versions; the Kinematic Deviation Score mean (KDSm) and worst score (KDSw) were evaluated for association with each other and subjective abnormality rating (Pearson's 'r' correlation), test-retest reliability (intra-class correlation coefficient (ICC)), and ability to quantify speed-related changes in abnormal upper limb movement (Cohen's d effect size (ES), % change scores). Very strong correlations existed between composite scores. The KDSm under-classified upper limb abnormality, whereas the KDSw captured the majority of ABI participants. All scores had moderate-strong correlations with subjective rating of abnormal upper limb movements (r = 0.54 - 0.79) and very strong test-retest reliability (ICCs > 0.81). The APSam demonstrated a 16% (ES = 0.76) walking speed-related increase in upper limb abnormality, whilst decreases were demonstrated in the KDSm 26% (ES 0.90) and KDSw 35% (ES 0.96). The APSam, KDSw, and number of abnormal joint axes comprehensively assess the whole upper limb abnormal movements, accurately classifies abnormality, and quantifies severity. This study illustrated notable presence of abnormal upper limb movements at self-selected walking speed and small increase at fast speeds. However, when scaled to HC variability, the fast walk kinematics became less abnormal due to increased HC movement variability.


Epidemiological features of HIV/AIDS in the Middle East and North Africa from 1990 to 2017.
The growing trend of HIV/AIDS is a major concern in the Middle East and North Africa (MENA) regions, as its incidence in the region has increased by 31% in the last decade. The study population in the countries of the MENA region included 21 countries with a population of approximately 400 million. The Global Burden of Disease database was used to calculate the number of HIV/AIDS cases. Modeling for each country is based on the availability and quality of data. The highest incidence rates of HIV/AIDS were in Sudan, United Arab Emirates (UAE), Tunisia, and Iran, respectively, and the highest mortality rates were in Sudan, UAE, Oman, and Morocco, respectively. The incidence, prevalence and mortality rates, as well as the disability adjusted life years (DALYs) rate declined in 2017 compared to 1990. The highest percentage of changes in DALY rates was reported for Turkey, the United Arab Emirates (UAE), and Sudan, respectively, and the lowest for Qatar, Kuwait, and Bahrain. In general, unsafe sex had the highest impact on the DALY index in all countries in the region except Iran and Bahrain. Policymakers should therefore be encouraged to develop harm reduction programs for people living with HIV, and invest globally in reducing HIV prevalence rates in commercial sex workers, people who inject drugs, and men who have sex with men in the region, as well as eliminating mother-to-child HIV transmission.


Levosimendan Postconditioning Attenuates Cardiomyocyte Apoptosis after Myocardial Infarction.
Levosimendan preconditioning has been shown to attenuate myocardial apoptosis in animal models. However, protective effects of levosimendan postconditioning against myocardial apoptosis following myocardial infarction (MI) have not been evaluated. Therefore, we investigated the effects of levosimendan postconditioning on myocardial apoptosis in MI rat models. In an anoxia/reoxygenation (A/R) model, H9c2 cells were pretreated with or without levosimendan postconditioning after which their apoptosis rates were assessed by flow cytometry, RT-qPCR, and western blot analyses. Then, postconditioning was performed with or without levosimendan in MI rat models. Myocardiocyte apoptosis was evaluated by echocardiography, TTC staining, TUNEL staining, immunohistochemical staining, RT-qPCR, and western blot analysis. Levosimendan postconditioning inhibited H9c2 cell apoptosis in A/R models by elevating Bcl-2 while suppressing Caspase-3 and Bax at both mRNA and protein levels. Moreover, it improved cardiac functions and reduced the left ventricle infarction area in MI rat models. Compared to the MI control group, cardiomyocyte apoptosis rates in the levosimendan postconditioning group were low. The reduced cardiomyocyte apoptosis rates were associated with downregulation of Bax and Caspase-3 as well as with upregulation of Bcl-2 at mRNA and protein levels. Levosimendan postconditioning of MI rat models protected against cardiomyocyte apoptosis, implying that it is a potential strategy for preventing cardiomyocyte apoptosis in the treatment of cardiac dysfunction following MI.


Surface effects on friction-induced fluid heating in nanochannel flows.
We investigate the mechanism of friction-induced fluid heating under the influence of surfaces. The temperature distributions of liquid argon and helium in nanoscale Poiseuille flows are studied through molecular dynamics simulations. It is found that the fluid heating is mainly caused by the viscous friction in the fluid when the external force is small and there is no slip at the fluid-solid interface. When the external force is larger than the fluid-surface binding force, the friction at the fluid-solid interface dominates over the internal friction of the fluid and is the major contribution to fluid heating. An asymmetric temperature gradient in the fluid is developed in the case of nonidentical walls and the general temperature gradient may change sign as the dominant heating factor changes from internal to interfacial friction with increasing external force. The effect of temperature on the fluid heating is also discussed.


Deciding in the dark: age differences in intuitive risk judgment.
Elevated levels of risky behavior in adolescence may signal developmental change in unconscious appraisal of risk. Yet, prior research examining adolescent risk judgment has used tasks that elicit conscious deliberation. The present study, in contrast, attempts to characterize age differences in (less conscious) intuitive impressions of risk. Participants (N = 282; ages 10-30) were presented with depictions of a range of risky and nonrisky activities. They were given 2.5 s to rate each activity on a continuous scale ranging from "bad idea" (low-risk favorability) to "good idea" (high-risk favorability). A curvilinear pattern was found, such that favorability ratings increased across adolescence and peaked around age 20. These results pose a challenge to developmental models that view early adolescence as the period of greatest predisposition toward risk taking; however, they are fairly consistent with age patterns for actual risk taking, at least with respect to crime, binge drinking, and unwanted pregnancy.


Only multiple autoantibodies to islet cells (ICA), insulin, GAD65, IA-2 and IA-2beta predict immune-mediated (Type 1) diabetes in relatives.
We report here our prospective study of 15,224 non-diabetic, first-degree relatives of probands with immune-mediated (type 1) diabetes (IMD), of which 135 were found to eventually develop diabetes. We determined islet cell, insulin, GAD65, insulinoma-associated antigen-2 and 2beta autoantibodies (ICA, IAA, GAD65A, IA-2A and IA-2betaA), on the first available serum samples. The latter three autoantibodies were however assayed on subsets of the relatives with and without ICA, IAA and/or GAD65A, plus most of the relatives who developed diabetes. Of the relatives who progressed to diabetes, 94% had at least one of these autoantibodies on the first screening, while ICA proved to be the most sensitive single marker (sensitivity 74%). Risk of diabetes was however negligible when ICA was found in the absence of the others (5-year risk=5.3%), but increased dramatically whenever two or more autoantibodies were present (5-year risk=28.2% and 66.2%, respectively). The most predictive combination of markers was ICA plus IA-2A and/or IA-2beta A. Loss of first phase insulin release to IVGTT also occurred only in those ICA-positive relatives who had one or more of the other autoantibodies. The data suggests that significant beta-cell damage is seen only when the underlying autoimmunity has spread to multiple antigenic islet cell determinants. Combinations of the autoantibodies occurred most often in relatives with the highest risk HLA-DR/DQ phenotypes. These data document that only relatives positive for at least two or more of these five autoantibodies are at significant risk of diabetes themselves. Intervention trials for the prevention of type 1 diabetes could be designed based on testing for these autoantibodies alone, without the need for HLA typing and IVGTT testing.


Phosphorylation of specific rat plasma membrane proteins during promotion of gamma-glutamyl transpeptidase-positive hepatic foci and inhibition by di(2-ethylhexyl)phthalate.
The protein kinase activity of isolated plasma membranes from the livers of rats treated with three promoting regimens was examined using both exogenous proteins and endogenous plasma membrane proteins as substrates. Male rats first received either an initiating dose (30 mg/kg) of the hepatocarcinogen diethylnitrosamine or the 0.9% NaCl solution vehicle by i.p. injection at 18 h following partial hepatectomy. Ten days later, the three promoting regimens were begun. These consisted of 10 weeks of treatment with either (a) a choline-deficient (CD) diet, (b) a choline-supplemented (CS) diet containing 0.06% phenobarbital (PHB) (CS plus PHB), or (c) a CD diet containing 0.06% PHB (CD plus PHB). In addition, two other groups of rats received either (a) a CS diet containing 2% di(2-ethylhexyl)phthalate (DEHP) (CS plus DEHP) or (b) a CD diet containing 2% DEHP (CD plus DEHP). DEHP is a widely used plasticizer and environmental contaminant which we have shown previously inhibits the development of putative preneoplastic gamma-glutamyl transpeptidase (GGT) positive foci in rat liver. Total liver plasma membrane protein kinase activity using both protamine sulfate and histone was cyclic adenosine 3':5'-monophosphate independent and did not appear to be a marker of promotion. Its activity was increased by both DEHP which suppresses the development of GGT positive foci and a CD diet which promotes the appearance of GGT positive foci. The CD, CS plus PHB, and CD plus PHB dietary regimens, which promote the appearance of GGT positive foci, induced the phosphorylation of a Mr 40,000 plasma membrane protein in vitro by endogenous protein kinases. Plasma membranes from DEHP-treated rats did not demonstrate phosphorylation of this Mr 40,000 protein. DEHP dietary treatment also blocked the ability of epidermal growth factor to enhance the phosphorylation of its Mr 175,000 receptor protein in isolated liver plasma membranes. These results suggest that the phosphorylation of a Mr 40,000 plasma membrane protein may be important to the early promotional phase of liver carcinogenesis, and that one mechanism by which DEHP inhibits the emergence of GGT positive foci may be by blocking the response of initiated cells to stimulation by epidermal growth factor.


Chemical assay for cyst(e)ine-rich peptides detects a novel intestinal peptide ZF-1, homologous to a single zinc-finger motif.
Cysteine is a relatively infrequent constituent of proteins, which in its thiol or half-cystine form contributes in a special manner to their three-dimensional structure. We show that in small cystine-containing peptides, the Cys content is always higher than the average in proteins in general. This observation makes it possible to search for new peptides by monitoring only their Cys content. We have developed a chemical assay for the detection of cyst(e)ine-rich peptides in tissue extracts. Using this assay we have isolated from porcine intestine a novel cysteine-rich peptide, which we denote ZF-1. ZF-1 is homologous to a single zinc-finger motif and has an acetylated N-terminus. This is the first demonstration of the existence of a processed single zinc-finger-like structure. The structural homology of ZF-1 to the zinc-finger motif, present in several metal-binding and DNA-binding proteins, suggests an important role of this peptide in metal transport and/or modulation of gene expression.


Detection of slime and methicillin resistance genes in Staphylococci isolated from nasal samples of patients with orthopaedic implants.
The purposes of the present study were (1) to determine the prevalence of mecA and femA genes, (2) to investigate the presence of icaA and icaD genes responsible for slime synthesis, and (3) to search in vitro slime synthesis by staphylococcal strains isolated from the nares of patients with orthopaedic implants using the Congo red agar (CRA) plate test. Staphylococci strains were defined by multiplex polymerase chain reaction (PCR) technique to determine intercellular adhesion genes icaA and icaD. Slime production capability was searched by the CRA plate test, phenotypically. Also, the presence of mecA and femA genes was determined by PCR in all strains. The presence of icaA and icaD was detected in 101 isolates of 134 (75.4%) strains. This ratio was 74.8% (89 of 119) among the Staphylococcus epidermidis and 80% (12 of 15) among the Staphylococcus aureus isolates. A total of 63.4% of all the strains were found to be icaA and icaD positive as well as slime-forming on the CRA plate test. The percentage of icaA- and icaD-negative strains was 36.6%, and all of them were negative on the CRA plate test. Although femA presence was detected in all 15 (11.2%) S. aureus isolates, a total of 5 (3.7%) isolates carried the mecA gene. The frequency of icaA and icaD genes was determined to be of high prevalence among staphylococcal isolates. The staphylococcal strains that were found in the nasal flora of patients with orthopaedic implants may be important potential sources of infection for these patients.


C-fos induction in forebrain areas of two different visual pathways during consolidation of sexual imprinting in the zebra finch (Taeniopygia guttata).
Two forebrain areas in the hyperpallium apicale and in the lateral nidopallium of isolated male zebra finches are highly active (2-deoxyglucose technique) on exposure to females for the first time, that is first courtship. These areas also demonstrate enhanced neuronal plasticity when screened with c-fos immunocytochemistry. Both are areas involved in the processing of visual information conveyed by the two major visual pathways in birds, strengthening our hypothesis that courtship in the zebra finch is a visually guided behaviour. First courtship and chased birds show enhanced c-fos induction in the hyperpallial area, which could represent neuronal activity reflecting changes in the immediate environment. The enhanced expression of fos in first courtship birds in lateral nidopallial neurons indicates imminent long-lasting changes at the synaptic level that form the substrate for imprinting, a stable form of learning in birds.


[Shaping of the migratory process in northern Mexico, 1930-1990].
"During the third decade of this century Mexican geographical structure began to change notoriously. Due to the strong influence of [the] North American economy, the north of Mexico became progressively one of the most important regions in the country, with the emergence of favorable perspectives of economic growth. Soon it became attractive to migration from the demographically pressed regions of Central Mexico. Thus, the north of Mexico was favored by the presence of qualified workers and a growing population. However, the region was not evenly populated, due to geographic, historic, and socio-economic factors that...[affect] the processes of migration and settlement. Some regions present important changes in their migratory flow, evidenced by the presence of new entities of origin and the disappearance of others." (SUMMARY IN ENG)


Comparison of posteromedial and subtalar release in surgical treatment of resistant clubfoot.
This preliminary study evalluated two surgical techniques for the treatment of resistant clubfoot: the posteromedial and the subtalar release. Two groups of matched patients with idiopathic clubfoot who underwent surgery between 1983 and 1995 were compared. In group 1 (12 patients, 18 feet), posteromedial release was performed. In this group, the results were satisfactory with a tendency to hypocorrection: 4 (22%) feet needed a secondary procedure (average follow-up: 97.8 months). Group 2 (12 patients, 17 feet) underwent complete subtalar release. The results were clinically better for group 2 (average follow-up: 38.8 months). Only 1 (5.9%) patient needed a secondary procedure. These results suggest complete subtalar release yields better postoperative correction than posteromedial release.


Strategies for combating dental anxiety.
Dental anxiety and subsequent avoidance of dental care and deterioration of oral health pose a significant problem for the dental profession. In an attempt to elucidate preferences of anxious dental patients, we gathered survey data from 121 persons at a small, private liberal arts college in the mid-Atlantic region of the United States. Half of the respondents experienced dental anxiety, and most of these (66 percent) attributed anxiety to fear of anticipated pain. The majority of anxious patients preferred a dentist to be friendly (93 percent), talkative (82 percent), and to have an office with adorned walls (89 percent) and a slightly cool temperature (63 percent). Patients who identified themselves as anxious also indicated that music in the background (89 percent) and magazines and books in the dental office (75 percent) were helpful. Anxious patients were more likely than non-anxious patients to prefer a male dentist (77 percent versus 52 percent). This finding was especially marked among anxious male respondents, 93 percent of whom preferred a male dentist compared to 73 percent of anxious female respondents. These survey data may assist dental professionals in understanding and combating patients' dental anxiety, in order to increase the frequency of dental visits and to prompt a corresponding restoration or maintenance of oral health.


From plan to action.
A strategic plan is your organizational touchstone Given the rapid rate of change in health care, your practice's capacity to succeed is based on its ability to adapt quickly; this, in turn, relies on the level of detail in the operational plan. A well-devised and detailed plan will enable your practice to navigate the waters of industry change. An operational plan begins with the practice's vision, values and mission.


Initial infectious disease screening evaluation of the international adoptee.
International adoptees are consistently exposed to unbelievable living conditions prior to being adopted that, coupled with malnourished states, substandard medical assessment and care, and unreliable immunizations, place them at significant risk for infectious diseases. In this second in a three-part series of topics related to the care of international adoptees, we discuss recommended infectious disease screening tests that can be provided by the primary care physician once the child arrives in the United States.


Value of sonohysterography in the diagnosis and management of abnormal uterine bleeding.
To assess the value of sonohysterography in the diagnosis and management of abnormal uterine bleeding. Sonohysterography was performed in 28 women (aged 29-55 years) in whom transvaginal sonography (TVS) suggested an abnormal endometrial echo (n = 14) or fibroids (n = 14). Its effect on diagnosis and treatment was studied. In the patients with an abnormal endometrial echo, sonohysterography depicted endometrial polyps (n = 9), intracavitary fibroids (n = 3), placental polyp (n = 1), and a normal cavity (n = 1). Hysteroscopic resection resolved the bleeding in 11 of 14 patients; surgery was obviated in one. In the group with fibroids, sonohysterography depicted small submucous fibroids amenable to hysteroscopic myomectomy (n = 5), a small mural fibroid with a normal cavity, which obviated surgical intervention (n = 4), and endometrial polyps, which altered the treatment plan (n = 1). Sonohysterography suggested the need for an abdominal myomectomy (n = 4) and alerted the surgeon to explore the uterine cavity in three patients. By helping elucidate the cause of bleeding, sonohysterography assisted in determining the therapeutic approach and often reduced the level of surgical intervention or obviated it altogether.


[Epidemiology of drug abuse and dependence].
Drug abuse or dependence in Japan has been characterized by three epidemics of methamphetamine abuse. In addition, solvent abuse has been predominant for a long time. Since 1995, with the start of the third epidemic of methamphetamine abuse, drug abuse or dependence in Japan has obviously changed, with an obvious decrease in solvent abuse; the stabilization of methamphetamine abuse; an increase in the abuse of such drugs as cannabis or MDMA, which do not have high potential to cause drug-induced psychosis; and the emergence of designer drugs. These changes imply a shift from conduct that leads to arrest to conduct that does not lead to arrest. Therefore, Japan is urged to deal with drug abuse and dependence using both a criminal model and a medical model.


Medicolegal considerations for office-based anesthesia in dentistry.
Over the past decade, there has been a virtual explosion in the demand and utilization of office-based ambulatory anesthesia services in dentistry. Not surprisingly, with this increased demand has come an increased exposure to medicolegal risks and concerns for the unwary or unprepared dental practitioner. This article provides the practitioner with a brief overview of the potential medicolegal risks and recent trends in litigation that may arise in today's office-based anesthesia practice.


Anti-inflammatory potential of newly synthesized 4-[(butylsulfinyl)methyl]-1,2-benzenediol in lipopolysaccharide-stimulated BV2 microglia.
In this study, we investigated the anti-inflammatory effects of newly synthesized 4-[(butylsulfinyl)methyl]-1,2-benzenediol (SMBD) in lipopolysaccharide (LPS)-stimulated BV2 microglia and the subsequent signaling events. Following stimulation with LPS, elevated production of nitric oxide (NO) and prostaglandin E2 (PGE2) was detected in BV2 cells; however, SMBD pretreatment inhibited the production of NO and PGE2 through suppressing gene expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively, at non-toxic concentrations. LPS-stimulated gene expression and production of interleukin (IL)-1β and tumor necrosis factor (TNF)-α were also significantly reduced by SMBD. The anti-inflammatory effects of SMBD were associated with suppression of LPS-induced nuclear translocation of nuclear factor-kappa B (NF-κB), and phosphorylation of mitogen-activated protein kinases (MAPKs) and Akt, a phosphatidylinositol 3-kinase (PI3K) downstream effector. Therefore, the present results demonstrate that SMBD down-regulates inflammatory gene expression by inhibiting the activation of NF-κB through interference with the activation of MAPKs and PI3K/Akt signaling. Taken together, our data suggest that SMBD may have potential to be developed into an effective anti-inflammatory agent.


Overexpression of satellite alpha transcripts leads to chromosomal instability via segregation errors at specific chromosomes.
The impairment of the stability of the chromosomal structure facilitates the abnormal segregation of chromosomes, thus increasing the risk of carcinogenesis. Chromosomal stability during segregation is managed by appropriate methylation at the centromere of chromosomes. Insufficient methylation, or hypomethylation, results in chromosomal instability. The centromere consists of satellite alpha repetitive sequences, which are ideal targets for DNA hypomethylation, resulting in the overexpression of satellite alpha transcript (SAT). The overexpression of SAT has been reported to induce the abnormal segregation of chromosomes. In this study, we verified the oncogenic pathway via chromosomal instability involving DNA hypomethylation and the overexpression of SAT. For this purpose, we constructed lentiviral vectors expressing SAT and control viruses and then infected human mammary epithelial cells with these vectors. The copy number alterations and segregation errors of chromosomes were evaluated by microarray-based comparative genomic hybridization (array CGH) and immunocytochemistry, respectively. The levels of hypomethylation of satellite alpha sequences were determined by MethyLight polymerase chain reaction. Clinical specimens from 45 patients with breast cancer were recruited to verify the data in vitro. The results of immunocytochemistry revealed that the incidence of segregation errors was significantly higher in the cells overexpressing SAT than in the controls. An array CGH identified the specific chromosomes of 8q and 20q as frequent sites of copy number alterations in cells with SAT overexpression, although no such sites were noted in the controls, which was consistent with the data from clinical specimens. A regression analysis revealed that the expression of SAT was significantly associated with the levels of hypomethylation of satellite alpha sequences. On the whole, the overexpression of SAT led to chromosomal instability via segregation errors at specific chromosomes in connection with DNA hypomethylation, which was also recognized in clinical specimens of patients with breast cancer. Thus, this oncogenic pathway may be involved in the development of breast cancer.


An experimental study on astrocytes promoting production of neural stem cells derived from mouse embryonic stem cells.
The production of neural stem cells (NSCs) derived from embryonic stem (ES) cells was usually very low according to previous studies, which was a major obstacle for meeting the needs of clinical application. This study aimed at investigating whether astrocytes could promote production of NSCs derived from ES cells in vitro. Mouse ES cells line-D3 was used to differentiate into NSCs with astrocytes as inducing stromal cells by means of three-stage differentiation procedure. Another group without astrocytes served as control. The totipotency of ES cells was identified by observation of cells' morphology and formation of teratoma in severe combined immunodeficiency disease (SCID) mice. The quantity and purity of NSCs derived from ES cells were analyzed using clonogenic assay, immunohistochemical staining and flow cytometry assay. The plasticity of NSCs was detected by differentiating test. Octamer-binding transcription factor 4 (Oct-4) and nestin, the specific marker genes of ES cells and NSCs respectively, were detected continuously using reverse transcription-polymerase chain reaction (RT-PCR) method to monitor the process of cell differentiation. The ES cells of D3 line could maintain the ability of differentiating into cellular derivations of all three primary germ layers after continuous passage culture. At the end of two-stage of inducing process, 23.2 +/- 3.5 neurospheres per plate formed in astrocyte-induced group and only 0.8 +/- 0.3 per plate in the control group (clonogenic assay, P < 0.01), and the ratio of nestin positive cells was (50.2 +/- 2.8)% in astrocyte-induced group and only (1.4 +/- 0.5)% in the control group (flow cytometry, P < 0.01). With the induction undergoing, the expression of Oct-4 gradually decreased and then disappeared, while the expression of nestin was increased step by step, and the ratio of nestin positive cells was up to 91.4% by the three-stage differentiation. The nestin positive cells could be further induced into neurons, astrocytes, and oligodendrocytes in differentiating medium supplemented with fetal calf serum. The results of differentiating test showed that the ratio of NF-200 and NSE positive cells was (42.7 +/- 2.6)% in astrocyte-induced group and only (11.2 +/- 1.8)% in the control group (P < 0.01). Astrocytes can not only increase the production of NSCs derived from ES cells but also promote the differentiation of NSCs toward neuronal lineage.


Major hepatectomy at interval debulking for stage IV ovarian carcinoma: a case report.
Previous studies have reported the results of hepatic resection for metastatic ovarian cancer at the time of primary cytoreductive surgery and at the time of recurrence. We present the first case of major hepatic resection performed at the time of interval cytoreduction for metastatic ovarian carcinoma. Interval debulking with hepatic resection may be a promising approach for patients left with bulky parenchymal liver metastasis after primary cytoreductive surgery.


[Adherent reaction among activated platelets, polymorphonuclear cells and vascular endothelial cells under thrombin stimulation or shear stress].
Platelet activation in addition to blood coagulation abnormality is regarded as a primary factor of thrombosis by atherosclerotic obstruction. Therefore, the platelet activation on atherosclerosis is considered to correlate with shear stress generated between blood cells and endothelial cells in blood flow. P-selectin on the surface of the platelet membrane is measured by flowcytometry as a marker of platelet activation. Herein, we examined the phenomena of platelet activation and adherent platelets with leukocytes (ad-P.L) on stored platelet concentration (PC) and chronic rheumatoid arthritis (RA), moreover, of the adherent platelets or polymorphonuclear cells (PMN) with endothelial cells (EC) in shear stress by using an apparatus we devised. The rate of platelet activation and ad-P.L increased in PC with storage, and the sensitivity of platelets to thrombin decreased. The rate of platelet activation and ad-P.L increased in RA in vivo. Many adherent platelets with EC were found at a low shear rate on normal EC but at a high shear rate on denatured EC without any specific adherent property. Adherent PMN with EC had several hundred times more denatured EC than normal EC and the relationship with shear rate disappeared on denatured EC. The platelet activation and relationship between platelets or leukocytes and EC as to the cause of thrombosis are important subjects for future studies.


MEF2 transcriptional activity maintains mitochondrial adaptation in cardiac pressure overload.
The transcription factor MEF2 is a downstream target for several hypertrophic signalling pathways in the heart, suggesting that MEF2 may act as a valuable therapeutic target in the treatment of heart failure. In this study, we investigated the potential benefits of overall MEF2 inhibition in a mouse model of chronic pressure overloading, by subjecting transgenic mice expressing a dominant negative form of MEF2 (DN-MEF2 Tg) in the heart, to transverse aortic constriction (TAC). Histological analysis revealed no major differences in cardiac remodelling between DN-MEF2 Tg and control mice after TAC. Surprisingly, echocardiographic analysis revealed that DN-MEF2 Tg mice had a decrease in cardiac function compared with control animals. Analysis of the mitochondrial respiratory chain showed that DN-MEF2 Tg mice displayed lower expression of NADH dehydrogenase subunit 6 (ND6), part of mitochondrial Complex I. The reduced expression of ND6 in DN-MEF2 Tg mice after pressure overload correlated with an increase in cell death secondary to overproduction of reactive oxygen species (ROS). Our data suggest that MEF2 transcriptional activity is required for mitochondrial function and its inhibition predisposes the heart to impaired mitochondrial function, overproduction of ROS, enhanced cell death, and cardiac dysfunction, following pressure overload.


Use of lipophilic cations to measure the membrane potential of oat leaf protoplasts.
Uptake of the lipophilic cation triphenylmethylphosphonium into mesophyll protoplasts of oat (Avena sativa L. cv. "Garry") approaches equilibrium at 3 to 4 hours. The resulting external and internal concentrations are then used with the Nernst equation to obtain a membrane potential of -62 millivolts, inside negative. Potentials calculated in this manner are depolarized by adding 2 mm sodium azide and 50 mum carbonyl cyanide m-chlorophenylhydrazone as well as by increasing the external proton and potassium concentrations. The depolarizations are qualitatively similar to those seen when oat mesoyphll cells are measured in situ with microelectrodes. It is concluded that due to the lack of turgor and fragility of protoplasts, estimations of their membrane potential may be made more reliably, under some conditions, with lipophilic cations than with microelectrodes.


Poly(methyl methacrylate) microchip affinity capillary gel electrophoresis of aptamer-protein complexes for the analysis of thrombin in plasma.
Thrombin generation in blood serves as an important marker for various hemostasis-related diseases and conditions. Analytical techniques currently utilized for determining the thrombin potential of patients rely primarily on the enzymatic activity of thrombin. Microfluidic-based ACE using fluorescently labeled aptamers as affinity probes could provide a simple and efficient technique for the real-time analysis of thrombin levels in plasma. In this study, aptamers were used for the analysis of thrombin by affinity microchip CGE. The CGE used a poly(methyl methacrylate) (PMMA) microfluidic device for the sorting of the affinity complexes with a linear polyacrylamide (LPA) serving as the sieving matrix. Due to the fact that the assay was run under nonequilibrium electrophoresis conditions, the presence of the sieving gel was found to stabilize the affinity complex, providing improved electrophoretic performance compared to free-solution electrophoresis. Two fluorescently labeled aptamer affinity probes, HD1 and HD22, which bind to exosites I and II, respectively, of thrombin were investigated. With an electric field strength of 300 V/cm, two well-resolved peaks corresponding to free aptamer and the thrombin-aptamer complex were obtained in less than 1 min of separation time with a run-to-run and chip-to-chip reproducibility (RSD) of migration times <10% using both aptamers. HD22 affinity assays of thrombin produced baseline-resolved peaks with favorable efficiency due to its higher binding affinity, whereas HD1 assays showed poorer resolution of the free aptamer and complex peaks. HD22 was used in determining the level of thrombin in human plasma. Assays were performed directly on plasma that was diluted to 10% v/v. Thrombin was successfully analyzed by microchip CGE at a concentration level of 543.5 nM for the human plasma sample.


Myofascial release of carpal tunnel syndrome.
Current treatment for carpal tunnel syndrome may be ineffective or associated with complications or recurrence. In the case reported here, a myofascial release by the physician combined with the patient's self-stretch reduced pain and numbness and improved electromyographic results. The manipulative approach releases the transverse carpal ligament,-and "opens" or dilates the canal. The patient stretches the wrist, digits, and thumb, including myofascial components. An aggressive, conservative approach lessens the need for surgery in mild to moderate cases. Studies with magnetic resonance imaging may be helpful to document canal size before and after treatment.


Impact of experimental genital mycoplasmosis on pregnancy outcome in Sprague-Dawley rats.
Specific-pathogen-free (SPF) female Sprague-Dawley rats were infected by intravaginal inoculation with 3 x 10(7) CFU of Mycoplasma pulmonis X1048 in 0.1 ml of Frey's broth or with an equal volume of sterile Frey's broth. A minimum of 10 days postinfection, rats were bred to noninfected males. Rats were necropsied at days 11, 14, and 18 of gestation and within 24 h of parturition. Throughout pregnancy, at least 50% of rats remained infected in the lower genital tract. At parturition, the major site of colonization was the respiratory tract (P = 0.02). M. pulmonis was not isolated from any site of any control rat. Pregnancy outcome was adversely affected by infection with M. pulmonis. Infected rats had significantly smaller litter sizes at day 18 of gestation (P < or = 0.01) and at term (P < or = 0.004). No statistically significant differences among the gestational stages in infected rats were noted for litter size. Total litter weight is a reflection of individual pup weight and of the number of pups born. Therefore, it was obvious that infected rats would have a significantly lower (P < or = 0.008) total litter weight than noninfected controls. However, when individual pup weights were considered, infected pups (n = 49) also had significantly lower (P < or = 0.0001) birth weights than did noninfected controls (n = 68). The incidence of an adverse pregnancy outcome at term (stillbirths, macerated fetuses, or resorptions) was higher (P < or = 0.01) in infected rats than in noninfected control rats. No stillborn pups or macerated fetuses were observed in any control term rats (n = 5). All control rats had live-born pups. Three infected rats had no live-born offspring. Resorptions were more common in infected rats than in control rats (P < or = 0.01). The mean number of resorptions per rat was greater in rats which went to term than in rats necropsied during gestation, indicating that the severity of disease was progressive. The rat is frequently the laboratory animal of choice for a wide variety of reproductive studies, and the experimental parameters that are most often measured (litter size, pup weight, and neonatal survival) were all adversely affected by genital mycoplasmosis. Genital mycoplasmosis is important as an animal model for the interaction of infectious agents and the host during pregnancy as well as in its own right as a confounding variable affecting research projects which use the rat as a model to study reproductive function and physiology.


Effects of TACE combined with microwave ablation on T lymphocyte subsets and prognosis in patients with liver cancer and analysis of safety.
To explore the influence of transcatheter hepatic arterial chemoembolization (TACE) combined with microwave ablation on T lymphocyte subsets and prognosis in patients with liver cancer and analyze the safety. The clinical data of 160 patients were retrospectively analyzed. The patients in the control group underwent TACE, while those in the observation group were treated with microwave ablation in addition to TACE. Then, the changes in the levels of T lymphocyte subsets, liver function indexes and alpha-fetoprotein (AFP) before and after treatment were compared between the two groups. After treatment, the levels of cluster of differentiation 3+ (CD3+), CD4+ and CD4+/CD8+ of patients were significantly increased in both groups, while the levels of CD8+ and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and AFP were overtly lowered, while the observation group had more obvious changes in the above-mentioned levels (p<0.05). The response rate and prognostic survival rate were evidently higher in the observation group than in the control group (p<0.05). The complications after treatment showed no significant difference between the two groups (p>0.05). Child-Pugh, tumor diameter and number of lesions were independent risk factors for the prognosis of survival of liver cancer patients undergoing TACE combined with microwave ablation (p<0.05). TACE combined with microwave ablation has relatively high efficacy and safety in the treatment of liver cancer, which can improve liver function, immune function and prognostic survival.


Townes-Brocks syndrome.
Townes-Brocks syndrome (TBS) is an autosomal dominant disorder with multiple malformations and variable expression. Major findings include external ear anomalies, hearing loss, preaxial polydactyly and triphalangeal thumbs, imperforate anus, and renal malformations. Most patients with Townes-Brocks syndrome have normal intelligence, although mental retardation has been noted in a few.


Reduction in insulitis following administration of IFN-gamma and TNF-alpha in the NOD mouse.
In insulin dependent diabetes mellitis (IDDM) beta cell destruction is associated with infiltration of the pancreatic islets by T lymphocytes and macrophages. Cytokine products from the infiltrating immunocytes not only have powerful immunoregulatory actions but also are capable of impairing islet cell functions and have thus been postulated to assume a central role in mediating anti-beta cell immunity and beta cell destruction. In an effort to explore further the role of cytokines in the pathogenesis of IDDM, we examined clinical, metabolic and pathological features of NOD/Wehi mice injected intraperitoneally with multiple doses of IFN-gamma and/or TNF-alpha. Blood glucose profiles were not significantly altered by injection of cytokines alone or in combination. Except for a hypoglycaemic rebound in mice injected with TNF-alpha, arginine stimulation tests revealed no disturbances in islet secretory function in cytokine injected mice. Compared with vehicle and cytokines alone, injection of IFN-gamma + TNF-alpha was associated with a variety of clinical and pathological changes including abdominal distention, piloerection, ascites, oedema, thymic atrophy, splenic enlargement and pancreatic distention. Histological examination of the pancreas in these mice revealed moderate to severe pancreatitis which included focal haemorrhagic necrosis, oedema and polymorphonuclear and mononuclear cell infiltration. The islets in these mice appeared normal morphologically and when stained for insulin. The injection of IFN-gamma + TNF-alpha, and to a lesser extent TNF-alpha alone, was associated with a significant reduction in the severity of insulitis. Examination of pancreatic MHC-class I and class II molecule expression revealed in mice given IFN-gamma + TNF-alpha, as compared with controls, significant and uniform induction of both these molecules on ductal and acinar cells; low level MHC-class II expression was also detectable on beta cells in these mice. MHC-class I molecules which were expressed at high levels by beta cells in control mice did not appear to change following administration of the cytokines alone or in combination. We conclude that despite their immunostimulatory actions in vitro and in other models in vivo, systemic administration of the cytokines IFN-gamma and/or TNF-alpha to NOD/Wehi mice does not activate or enhance, and may actually suppress, anti-beta cell immunity in this model.


Printed materials for an aging population: design considerations.
By the year 2020, 25% of the American population will be fifty-five or older. As this population ages, changes within the aging eye will necessitate changes in the way we present text, since approximately 85% of all learning occurs through vision. Educators need to become aware of these changes and begin designing written materials that can communicate effectively with this population. This paper includes information about some of the problems associated with the aging eye and design strategies that can enable the older adult to continue learning, working, and enjoying the written word.


Enhanced degradation of carbon tetrachloride by sodium percarbonate activated with ferrous ion in the presence of ethyl alcohol.
In this study, the degradation performance of carbon tetrachloride (CT) by sodium percarbonate (SPC) activated with Fe(II) in the presence of ethyl alcohol (EA) was investigated. The experimental results showed that CT could be readily degraded and the optimal EA/Fe(II)/SPC/CT molar ratio for CT reduction was 100/50/20/1. Superoxide radical anion ( ) and hydroxyethyl radical (•CHCH3OH, HER) were the predominant radical species responsible for CT degradation and EA could regulate the generation of and HER in the system. Further investigation for the solution matrix effects suggested that Cl-, , , and humic acid had negligible influences on CT degradation, while had negative effect in EA/Fe(II)/SPC system. On the other hand, the application of SPC/Fe(II)/EA technique is favorable to acidic condition is effective at a wide pH range of 3.0-7.0. In summary, CT degradation in Fe(II)-activated SPC system can be significantly promoted by addition of solvents, and these findings provide an innovative technology for the degradation of highly oxidized organic contaminants.


What potential role is there for medication treatment in anorexia nervosa?
To review selected issues regarding the development of drug treatments for anorexia nervosa (AN). The existing pharmacotherapy literature for AN is reviewed, and the theoretical and practical considerations are discussed. A very wide variety of drugs have been examined in AN, generally with negative results. There are a number of potential reasons for this finding, including compliance, nutritional deficits, selection of the wrong targets or the wrong outcome measures, use of monotherapy, lack of animal models, or factors intrinsic to AN. Pharmacotherapy provides little benefit in the treatment of AN at present. Several strategies might lead to the identification of more effective agents, including new measurement strategies, identification of novel pharmacologic targets, and consideration of a clinical trials network.


A Monoallelic Variant in REST Is Associated with Non-Syndromic Autosomal Dominant Hearing Impairment in a South African Family.
Hearing impairment (HI) is a sensory disorder with a prevalence of 0.0055 live births in South Africa. DNA samples from a South African family presenting with progressive, autosomal dominant non-syndromic HI were subjected to whole-exome sequencing, and a novel monoallelic variant in REST [c.1244GC; p.(C415S)], was identified as the putative causative variant. The co-segregation of the variant was confirmed with Sanger Sequencing. The variant is absent from databases, 103 healthy South African controls, and 52 South African probands with isolated HI. In silico analysis indicates that the p.C415S variant in REST substitutes a conserved cysteine and results in changes to the surrounding secondary structure and the disulphide bonds, culminating in alteration of the tertiary structure of REST. Localization studies using ectopically expressed GFP-tagged Wild type (WT) and mutant REST in HEK-293 cells show that WT REST localizes exclusively to the nucleus; however, the mutant protein localizes throughout the cell. Additionally, mutant REST has an impaired ability to repress its known target AF1q. The data demonstrates that the identified mutation compromises the function of REST and support its implication in HI. This study is the second report, worldwide, to implicate REST in HI and suggests that it should be included in diagnostic HI panels.