Transverse-Field Ising Dynamics in a Rydberg-Dressed Atomic Gas.

We report on the realization of long-range Ising interactions in a cold gas of cesium atoms by Rydberg dressing. The interactions are enhanced by coupling to Rydberg states in the vicinity of a Förster resonance. We characterize the interactions by measuring the mean-field shift of the clock transition via Ramsey spectroscopy, observing one-axis twisting dynamics. We furthermore emulate a transverse-field Ising model by periodic application of a microwave field and detect dynamical signatures of the paramagnetic-ferromagnetic phase transition. Our results highlight the power of optical addressing for achieving local and dynamical control of interactions, enabling prospects ranging from investigating Floquet quantum criticality to producing tunable-range spin squeezing.

Non-indigenous macrozoobenthic species on hard substrata of selected harbours in the Adriatic Sea.

The intense shipping traffic characterising the Adriatic Sea favours the spread of marine organisms. Yet, a study of 12 Adriatic ports (4 on the western side and 8 on the eastern side of the basin) found that non-indigenous species (NIS) accounted for only 4% of the benthic communities settled on hard substrates. The cirripeds Amphibalanus amphitrite and Balanus trigonus, found in 8 harbours, were the most common invaders followed by Amphibalanus eburneus, the ascidian Styela plicata, and the bivalve Magallana gigas. The highest percentage of NIS was recorded in Venice and Ploce, the harbours with the least rich native communities; the lowest percentage was retrieved in Trieste, Koper, Pula, and Rijeka, the harbours hosting the highest species diversity. In contrast, the ports of Bari and Ancona showed both high NIS percentages and highly diversified communities.

Detecting the occurrence of indigenous and non-indigenous megafauna through fishermen knowledge: A complementary tool to coastal and port surveys.

Marine bioinvasions and other rapid biodiversity changes require today integrating existing monitoring tools with other complementary detection strategies to provide a more efficient management. Here we explored the efficacy of fishermen observations and traditional port surveys to effectively track the occurrence of both indigenous and non-indigenous megafauna in the Adriatic Sea. This consisted mainly of mobile taxa such as fishes, crustaceans and molluscs. Port surveys using traps and nets within 10 major Adriatic harbours, were compared with the information obtained from 153 interviews with local fishermen. Information gathered by traps and nets varied significantly and generally resulted of limited efficacy in exotic species detection. Interviews allowed tracking the occurrence of new species through time and space, providing complementary knowledge at the low cost. This combined approach improves our capability of being informed on the arrival of species of different origin, providing a more rational, improved basis for environmental management and decision making.

Correlation between ECG changes and early left ventricular remodeling in preadolescent footballers.

The aim of this study was to assess the early electrocardiogram (ECG) changes induced by physical training in preadolescent elite footballers. This study included 94 preadolescent highly trained male footballers (FG) competing in Serbian Football League (minimum of 7 training hours/week) and 47 age-matched healthy male controls (less than 2 training hours/week) (CG). They were screened by ECG and echocardiography at a tertiary referral cardio center. Sokolow-Lyon index was used as a voltage electrocardiographic criterion for left ventricular hypertrophy diagnosis. Characteristic ECG intervals and voltage were compared and reference range was given for preadolescent footballers. Highly significant differences between FG and CG were registered in all ECG parameters: P-wave voltage (p < 0.001), S-wave (V1 or V2 lead) voltage (p < 0.001), R-wave (V5 and V6 lead) voltage (p < 0.001), ECG sum of S V1-2 + R V5-6 (p < 0.001), T-wave voltage (p < 0.001), QRS complex duration (p < 0.001), T-wave duration (p < 0.001), QTc interval duration (p < 0.001), and R/T ratio (p < 0.001). No differences were found in PQ interval duration between these two groups (p > 0.05). During 6-year follow-up period, there was no adverse cardiac event in these footballers. None of them expressed pathological ECG changes. Benign ECG changes are presented in the early stage of athlete's heart remodeling, but they are not related to pathological ECG changes and they should be regarded as ECG pattern of LV remodeling.

Survivin expression in patients with newly diagnosed nodal diffuse large B cell lymphoma (DLBCL).

Survivin is one of the inhibitors of apoptosis proteins (IAP) that might play an important role in the pathogenesis of diffuse large B cell lymphoma (DLBCL). The present study was designed to investigate the clinical and prognostic significance of survivin expression in nodal DLBCL. We analyzed lymph node biopsy specimens obtained from 56 patients with newly diagnosed nodal DLBCL, treated with immunochemotherapy (R-CHOP). The expression of survivin was analyzed using the standard immunohistochemical method on formalin-fixed and routinely processed paraffin-embedded lymph node specimens and evaluated semiquantitatively as a percentage of tumor cells. Survivin immunoexpression (>45 % positive tumor cells) was found in 22 (39.28 %) and observed as cytoplasmic staining in 15 patients, or mixed (cytoplasmic and nuclear) staining in 7 patients. A significant difference in survivin immunoexpression was noticed between the GCB and the non-GCB subtypes of DLBCL (p = 0.031). However, survivin immunoexpression had no significant association with IPI, "bulky" disease, extranodal localization, hemoglobin, Ki-67 immunoexpression or other clinicopathological parameters. A univariate analysis showed that survivin positivity was an unfavorable factor for therapy response and a predictor of shorter survival in patients with DLBCL (p = 0.048 and p = 0.034, respectively). Patients with survivin overexpression experienced a relapse more often than patients without expression of this apoptotic protein (27.3 vs. 11.8 %), but this difference did not reach statistical significance (p = 0.131). The results of this study showed that disregulation of survivin expression had an important role in the determination of the course of the disease in patients with nodal DLBCL treated with R-CHOP. Therefore, survivin represents a potential target for therapeutic intervention in DLBCL.

Influence of antiphospholipid antibody levels and type on thrombotic manifestations: results from the Serbian National Cohort Study.

Repeated thromboses are the most frequent clinical manifestation of antiphospholipid syndrome (APS) in the presence of antiphospholipid antibodies (aPL). The objective of this study was to observe the prevalence and localization of thrombosis, and to investigate the importance of aPL type and level for thrombosis-related events in patients diagnosed with APS. These are the first results of patients enrolled in Serbian National Cohort Study which comprises 256 patients: 162 with primary antiphospholipid syndrome (PAPS) and 94 with APS associated with systemic lupus erythematosus (SLE). aPL analysis included detection of aCL (IgG/IgM), ß(2)GPI, and lupus anticoagulant. Thrombosis was diagnosed in 119 (46.5%) patients, with higher prevalence in PAPS compared with SLE patients (51.2% and 38.3%, respectively, p = 0.045). There was similar prevalence of arterial thrombosis in PAPS and SLE groups (34.6% and 34%, respectively, p = 0.932) although venous thrombosis was more frequent in PAPS (25.9% and 8.5%, respectively, p = 0.001). Thrombosis was observed in 92 (55.8%) patients who had more than one type of antibody (category I), in 13 (41.9%) patients with category IIa, in 19 (46.3%) patients with category IIb, and in 73 (44.2%) patients with category IIc (p = 0.10). The patients with thrombosis were older than those without thrombosis (49.8 and 39.8 years, respectively, p = 0.001). Overall, older age was a risk factor for thrombosis. The prevalence of venous thrombosis was higher in the PAPS group, but with lower frequency than in literature data. Any aPL type and level is a risk factor for thrombosis.

Biological and clinical features of non-Hodgkin's lymphoma in the elderly.

PURPOSE: The incidence of non-Hodgkin's lymphomas (NHLs) in elderly people has increased in recent years because the world population is getting older. The aim of this study was to compare the biological and clinical features in patients diagnosed with NHLs younger and older than 65 years, and the possible influence of age on the choice of optimal therapeutic approach. METHODS: We retrospectively evaluated 193 patients with NHLs: 111 (68%) were <65 years and 82 (42%) ≥65 years. The following parameters were analysed: age, gender, clinical stage, International Prognostic Index (IPI), histological type, presence of B symptoms, disease localization, presence of bulky mass, Karnofsky performance status (PS), comorbidities, blood counts, liver and renal function and serum LDH. RESULTS: Elderly patients had statistically more frequent indolent NHLs (p=0.036), IPI 3 and 4 (p<0.0001), presence of comorbidities (p<0.001), and less frequent presence of bulky disease (p7equals;0.043). Response to therapy was different in the 2 age groups: 29% of patients ≥65 years achieved complete remission (CR) in contrast to 71% of patients <65 years (p<0.001). The most frequent cause of death was disease progression (PD) (86% of younger patients and 71% of elderly patients (p7equals;0.150). Older patients died more frequently because of comorbidities compared younger ones (21 and 107percnt;, respectively; p=0.250), and had more complications of therapy (8.1 and 47percnt;, respectively (p=0.320). Overall survival (OS) was shorter in older patients in all lymphoma types: indolent lymphoma (36 vs. 17 months), aggressive (22 vs. 20 months) and very aggressive (14 vs. 1 months). Multivariate analysis showed that parameters for shorter survival in the elderly were Karnofsky PS <60, increased serum LDH and treatment toxicity. CONCLUSION: In elderly NHLs patients, treatment response and survival are significantly poorer. Since older patients mostly died of PD, they should be treated with standard regimens and best supportive measures.

Clinical and histopathological study of angiogenesis in multiple myeloma.

PURPOSE: Angiogenesis is an essential component in the growth and progression of multiple myeloma (MM). We studied the clinical significance of angiogenesis in patients with MM estimated by precise counting of the number of vessels (i.e. microvessel density, MVD) and compared these results with the results obtained using semi-quantitative grading of angiogenesis. METHODS: Fifty-nine newly diagnosed cases of MM were analyzed with respect to clinical features, laboratory findings, histological features, angiogenesis parameters, and response to treatment. Bone marrow microvessels were examined using immunohistochemical staining for CD34. Bone marrow angiogenesis was estimated by two different methods. The mean number of vessels per area in each sample was characterized as the MVD. Microvessels were counted manually on light microscopy in 3 hot spots at ×400 magnification. Semiquantitative estimation of angiogenesis was based on visual assessment of slides at ×100 magnification. Each slide was assigned as low, intermediate or high intensity of angiogenesis. RESULTS: The median MVD was 15 vessels per 3 hot spots (range 1-89). Intensity of angiogenesis was assigned as low in 24 (40.7%) patients, intermediate in 17 (28.8%) and high in 18 (30.5%). Significant correlation between intensity of angiogenesis (estimated using both methods) and histological grade, extent of bone marrow infiltration, proliferative activity of myeloma cells and poor survival was found. Semiquantitatively assessed intensity of angiogenesis additionally correlated with clinical stage. There was a statistically highly significant correlation between MVD and semi-quantitatively estimated intensity of angiogenesis (p <0.001). CONCLUSION: Tumor-associated angiogenesis is an important prognostic feature in MM and should be routinely done on bone marrow biopsies of these patients. Simple semiquantitative grading of angiogenesis can be recommended for daily practice, as an alternative method for complicated and time-consuming estimation of MVD.

[Treatment of angioid streaks with anti-VEGF]. / Liecba angioid streaks (lakové trhliny) pomocou anti-VEGF.

PURPOSE: To evaluate the possibility to treat the chorioidal neovascularisation in angioid streaks with the help of Bevacizumab. Chorioidal neovascularisation is here the main reason responsible for destroying the vision and affects about 70-85% of patients with this disease. MATERIAL AND METHODS: 50 years old woman with 2 weeks anamnesis of worsening of vision on left eye. She claims deformed view in the middle of the visual field and mild decrease of visual acuity. BCVA was 0.9 and examination with Amsler grid showed line distorsion in the central part. After fundus examination, angiography and OCT we set diagnosis: angioid streaks complicated by subfoveal chorioidal neovascularisation. We proposed patient treatment with intravitreal Bevacizumab and subsequently started the therapy. RESULTS: One week after bevacizumab application, patient claims vanishing of vision distortion. In four weeks metamorphopsis completely disappeared and BCVA reached 1.2. OCT and FAG showed less leakage. After initial improvement and 7 months of stand still there comes again to vision deterioration (BCVA 0.7). We were obliged to reinject 1.25 mg of Bevacizumab and VA improved to 0.9 and also the deformation was less. Three months after second injection VA was again decreased and patient was treated with third injection. Patient is followed up for period of 12 months with mild deformation of picture and VA 0.7. It was not observed any side effect of treatment. CONCLUSIONS: The treatment of the chorioidal neovascularisation in angioid streaks is another possibility with the help of Bevacizumab.With this treatment can be delayed the devastation of VA with subfoveal neovascularization. It seems that the treatment is only temporally and during the 12 months follow up came to a few relapse.

[The treatment of the rubeosis of the iris and the neovascular glaucoma in proliferative diabetic retinopathy by means of anti-VEGF]. / Liecba rubeózy dúhovky a neovaskulárneho glaukómu pri proliferatívnej diabetickej retinopatii pomocou anti-VEGF.

The rubeosis of the iris is a serious complication especially in diabetic retinopathy and retinal veins occlusion. Cytokines, especially the vascular growing factor (VEGF), are responsible for the forming of new vessels. The treatment that inhibits the effect of the VEGF presents new possibilities in the neovascular diseases treatment. Bevacizumab (Avastin) is an anti-VEGF antibody that blocks all forms of VEGF-A. In three eyes with proliferative diabetic retinopathy and neovascularization of the iris and the anterior chamber angle, the dose of 1.25 mg of Avastin was applied intravitrealy. Just one week after the application of the drug, the decrease of the leakage on the iris, and the total disappearance of the neovascularization in three weeks were visible on the fluorescein angiogram. The recurrence of the neovascularization was found in one eye after three months and the treatment had to be repeated. Nine months after the second application, the disease is stabilized without the neovascularization. The intraocular pressure was elevated in two eyes before the application of Avastin, and was refractive to the treatment. After the disappearance of the neovascularization, the intraocular pressure was normalized and it was possible to terminate the antiglaucomatous therapy. The bevacizumab intravitreal treatment of the neovascularization of the iris and the anterior chamber angle was proved to be efficient, the neovascularization disappeared and the intraocular pressure was normalized. There were no side effects after the bevacizumab applications in any of our patients.

Plasmacytoma of the lung: an indolent disease resistant to conventional myeloma treatment: report of a case.

Solitary lung plasmacytoma is a rare form of plasma cell tumors. The case of a 56-yr-old man is presented, who had a massive tumor of the right pulmonary apex. Percutaneous transthoracic lung biopsy demonstrated a tumor-cell population consisting of mature plasma cells, proplasmacytes, and rare plasmablasts. Immunohistochemically, the cells were CD79a+, kappa+, cyclin D1-, p53-, MDR-. Proliferative index was low (number of Ki-67+ tumor cells was 8%). Serum and urine immunoelectrophoresis did not show the presence of paraprotein. Screening for multiple myeloma with skeletal X-ray survey and bone marrow biopsy were negative. Radiotherapy and chemotherapy with alkylating agents were ineffective. However, the course of the disease is indolent and the patient is well, alive, and with no signs of multiple myeloma >5 yr after the diagnosis was established. Some pathogenetic aspects of tumor resistance to conventional myeloma treatment in this case are discussed.

Immunohistochemical analysis of cyclin D1 and p53 in multiple myeloma: relationship to proliferative activity and prognostic significance.

Conflicting data are reported on the clinical significance of cyclin D1 deregulation in multiple myeloma. The aim of this study was to evaluate the incidence and prognostic significance of cyclin D1 expression and p53 mutations in multiple myeloma, as well as the relationship of their expression with selected clinical data, histological features, and proliferative activity of myeloma cells. We analyzed bone marrow biopsy specimens obtained from 59 patients with newly diagnosed multiple myeloma. Expression of cyclin D1 and p53 was analyzed using standard immunohistochemical method of B5-fixed and routinely processed paraffin-embedded bone marrow specimens. Cyclin D1 was overexpressed in 14/59 (27%) and p53 in 5/59 (8.5%) specimens. There was no significant correlation between cyclin D1 overexpression and age, gender, clinical stage (Durie-Salmon classification), extent of osteolytic lesions, type of monoclonal protein, hemoglobin concentration, platelet count, serum concentration of creatinine, calcium, C-reactive protein, and beta2-microglobulin. No association was observed between the expression of cyclin D1 and the extent of bone marrow infiltration, histological grade, proliferative activity index (measured with Ki-67 immunoreactivity) and response to therapy. No significant difference was observed regarding overall survival between cyclin D1 positive and cyclin D1 negative patients (29 vs 36 mo, p = 0.76). Results of this study did not revealed prognostic significance of cyclin D1 overexpression in multiple myeloma. Mutations of p53 gene are rare events in myeloma, suggesting their limited role in the pathogenesis of the disease.

Cervical acid phosphatase: a biomarker of cervical dysplasia and a potential surrogate endpoint for colposcopy.

BACKGROUND: In 2000, cervical acid phosphatase (CAP) has been recently described as a biomarker labeling abnormal squamous cells on Pap smears (USPTO #6,143,512). The enzyme activity is presented as a red, granular deposit on a modified Papanicolaou background. This unique property was utilized for development of MarkPap technology intended for cervical cancer screening. MATERIAL/PATIENTS & METHODS: We conduct a multicenter, random assignment, assessor blinded, 2-group (test and control), split-sample designed clinical trial on 1,500 subject/specimens to assess safety and efficacy of the new test, in comparison with the control, for cervical cancer screening in standard Pap test environment. Safety is measured with frequency, severity and relation of adverse events. Efficacy is measured with primary endpoints (portion of positive/abnormal specimens detected, and the false negative rate). At the end of the follow-up period (two years) when the study will be completed, other efficacy endpoints such as accuracy (sensitivity/specificity) and predictive values will be added to the method evaluation. Here we present in interim analysis. RESULTS: In April 2003, the recruitment was completed and the first twelve hundred cases have been evaluated. There was no serious or related adverse event in both groups. Minor, unrelated adverse events were rare and insignificantly distributed in both groups. PRIMARY ENDPOINTS: A: Portion of positive/abnormal specimens detected: Pe (new test) = 0.166, Ps (Pap control): 0.082; Ps' (ACS reported value for US in year 2000): 0.07. Pe >/= Ps + delta, for delta = 0.5Ps. B. False negative rate: Pe = 0.05, Ps' = 0.10. Confidence intervals: 95% CI: Test [0.148-0.193], Pap control [0.068-0.098]. OR = 2.26. chi2 = 40.69101 is greater than the critical value of 3.841 (P < 0.01). CONCLUSION: We concluded that CAP had added to visibility of Pap test and has enabled cytoscreeners to significantly improve the detection of positive/abnormal specimens and reduce false negative rate. We discuss this unique property of CAP with emphasis on using it as a surrogate endpoint for colposcopy and eventual removal of a cervical lesion that, if untreated, could progress into cancer.

Characterization of carrot pectin methylesterase.

The most alkaline form of pectin methylesterase was purified from ripe carrot roots and used for structural analysis. Determination of an N-terminal blocking group and of the primary structure allowed comparisons with other forms, and facilitated crystallographic determination of the three-dimensional structure. The mature enzyme has 319 residues and the N-terminal blocking group was shown to be a pyroglutamyl residue derived from a glutaminyl cyclization. Few other methylesterases have been isolated and assigned to exact mature forms, and together with the present enzyme, only two have been analyzed in three-dimensional structure. However, comparison of 39 forms, mainly from GenBank data, reveals clear relationships and identifies subgroups of this enzyme type, deviating in structure but centering around two functionally important and conserved Asp residues at positions 136 and 157 in the carrot enzyme.

Pectin degrading glycoside hydrolases of family 28: sequence-structural features, specificities and evolution.

Family 28 belongs to the largest families of glycoside hydrolases. It covers several enzyme specificities of bacterial, fungal, plant and insect origins. This study deals with all available amino acid sequences of family 28 members. First, it focuses on the detailed analysis of 115 sequences of polygalacturonases yielding their evolutionary tree. The large data set allowed modification of some of the existing family 28 sequence characteristics and to draw the sequence features specific for bacterial and fungal exopolygalacturonases discriminating them from the endopolygalacturonases. The evolutionary tree reflects both the taxonomy and specificity so that bacterial, fungal and plant enzymes form their own clusters, the endo- and exo-mode of action being respected, too. The only insect (animal) representative is most related to fungal endopolygalacturonases. The present study brings further: (i) the analysis of available rhamnogalacturonase sequences; (ii) the elucidation of relatedness between the recently added member, the endo-xylogalacturonan hydrolase and the rest of the family; and (iii) revealing the sequence features characteristic of the individual enzyme specificities and the evolutionary relationships within the entire family 28. The disulfides common for the individual enzyme groups were also proposed. With regard to functionally important residues of polygalacturonases, xylogalacturonan hydrolase possesses all of them, while the rhamnogalacturonases, known to lack the histidine residue (His223; Aspergillus niger polygalacturonase II numbering), have a further tyrosine (Tyr291) replaced by a conserved tryptophan. Evolutionarily, the xylogalacturonan hydrolase is most related to fungal exopolygalacturonases and the rhamnogalacturonases form their own cluster on the adjacent branch.

Cell cross-contamination in cell cultures: the silent and neglected danger.

Cell cross-contamination in cell cultures is a common problem during cell culturing and use. Contamination invalidates research results, compromises the comparison of results between laboratories, reduces reproducibility required in industrial production of cell lines, and may lead to unusable therapeutic products. The problem can be solved by increasing the awareness of its seriousness and by introducing regular quality control of cell cross-contamination in every laboratory where cells are grown and used.

The glycoprotein character of multiple forms of Aspergillus polygalacturonase.

Comparisons of known primary structures of polygalacturonases show that extent and localization of potential N-glycosylation sites differ. Some sites are similar in position and adjacent to strictly conserved residues at the potential active site. The presence of N-acetylglucosamine and mannose in the molecules of two homogeneous, major Aspergillus sp. polygalacturonase forms was confirmed by IR spectroscopy. The purification method, based on interaction of the carbohydrate part with concanavalin A immobilized on chlorotriazine bead cellulose, was optimized. Deglycosylation with N-glycosidase F under denaturating and nondenaturating conditions led to molecular mass decreases followed by complete inactivation of the polygalacturonase enzyme activity. These results show the importance of glycosylation in these protein forms, while the comparative patterns establish both variability and some similarities in overall glycosylation architectures.

An essential tyrosine residue of Aspergillus polygalacturonase.

Based on strict conservation of a tyrosine residue in 24 polygalacturonases, tyrosine modification was assessed in two different forms of the Aspergillus enzyme. The second subform was unknown in structure but submitted to sequence analysis and was found also to have the conserved tyrosine residue. Results of chemical modifications are consistent in showing inactivation of the proteins with all tyrosine-reactive agents tested, acetic anhydride, N-acetyl imidazole, and tetranitromethane. Furthermore, after acetylation, regeneration of enzyme activity was possible with hydroxylamine. Spectrophotometric pH titration showed that one accessible tyrosine residue is ionized at pH 9.3-9.5, whereas the remaining, masked residues are all ionized at pH 10.5. It is concluded that one tyrosine residue is catalytically important, in agreement with the inactivation and reactivation data, that this residue is accessible, and that it is likely to correspond to the strictly conserved residue observed in all forms.