Effect of vitamin E-enhanced highly cross-linked polyethylene on wear rate and particle debris in anatomic total shoulder arthroplasty: a biomechanical comparison to ultrahigh-molecular-weight polyethylene.

BACKGROUND: Particle-induced osteolysis resulting from polyethylene wear remains a source of implant failure in anatomic total shoulder designs. Modern polyethylene components are irradiated in an oxygen-free environment to induce cross-linking, but reducing the resulting free radicals with melting or heat annealing can compromise the component's mechanical properties. Vitamin E has been introduced as an adjuvant to thermal treatments. Anatomic shoulder arthroplasty models with a ceramic head component have demonstrated that vitamin E-enhanced polyethylene show improved wear compared with highly cross-linked polyethylene (HXLPE). This study aimed to assess the biomechanical wear properties and particle size characteristics of a novel vitamin E-enhanced highly cross-linked polyethylene (VEXPE) glenoid compared to a conventional ultrahigh-molecular-weight polyethylene (UHMWPE) glenoid against a cobalt chromium molybdenum (CoCrMo) head component. METHODS: Biomechanical wear testing was performed to compare the VEXPE glenoid to UHMWPE glenoid with regard to pristine polyethylene wear and abrasive endurance against a polished CoCrMo alloy humeral head in an anatomic shoulder wear-simulation model. Cumulative mass loss (milligrams) was recorded, and wear rate calculated (milligrams per megacycle [Mc]). Under pristine wear conditions, particle analysis was performed, and functional biologic activity (FBA) was calculated to estimate particle debris osteolytic potential. In addition, 95% confidence intervals for all testing conditions were calculated. RESULTS: The average pristine wear rate was statistically significantly lower for the VEXPE glenoid compared with the HXLPE glenoid (0.81 ± 0.64 mg/Mc vs. 7.00 ± 0.45 mg/Mc) (P < .05). Under abrasive wear conditions, the VEXPE glenoid had a statistically significant lower average wear rate compared with the UHMWPE glenoid comparator device (18.93 ± 5.80 mg/Mc vs. 40.47 ± 2.63 mg/Mc) (P < .05). The VEXPE glenoid demonstrated a statistically significant improvement in FBA compared with the HXLPE glenoid (0.21 ± 0.21 vs. 1.54 ± 0.49 (P < .05). CONCLUSIONS: A new anatomic glenoid component with VEXPE demonstrated significantly improved pristine and abrasive wear properties with lower osteolytic particle debris potential compared with a conventional UHMWPE glenoid component. Vitamin E-enhanced polyethylene shows early promise in shoulder arthroplasty components. Long-term clinical and radiographic investigation needs to be performed to verify if these biomechanical wear properties translate to diminished long-term wear, osteolysis, and loosening.

Basic information for identifying psychological disorders caused by malignant disease.

BACKGROUND: Improvements in cancer dia-gnosis and treatment explain a substantial increase in the number of patients chronically affected by or recovering from cancer. This is a fragile population, physically, psychologically and socially affected by the consequences of the disease and the associated treatment. The National Comprehensive Cancer Network (NCCN) reacted to this fact, creating the NCCN guidelines for survivorship. They provide screening, evaluation and treatment recommendations for the consequences of cancer and cancer treatment. PURPOSE: Inspired by this NCCN recommendation, we drew up this article pointing out the psychological issues like anxiety, depression and fatigue in order to help the physicians refer their patients timely to psychologic or psychiatric care.

Microfluidic photoreactor to treat neonatal jaundice.

While in most cases, jaundice can be effectively treated using phototherapy, severe cases require exchange transfusion, a relatively risky procedure in which the neonate's bilirubin-rich blood is replaced with donor blood. Here, we examine extracorporeal blood treatment in a microfluidic photoreactor as an alternative to exchange transfusion. This new treatment approach relies on the same principle as phototherapy but leverages microfluidics to speed up bilirubin removal. Our results demonstrate that high-intensity light at 470 nm can be used to rapidly reduce bilirubin levels without causing appreciable damage to DNA in blood cells. Light at 470 nm was more effective than light at 505 nm. Studies in Gunn rats show that photoreactor treatment for 4 h significantly reduces bilirubin levels, similar to the bilirubin reduction observed for exchange transfusion and on a similar time scale. Predictions for human neonates demonstrate that this new treatment approach is expected to exceed the performance of exchange transfusion using a low blood flow rate and priming volume, which will facilitate vascular access and improve safety.

Atomic force microscopy correlates antimetastatic potentials of HepG2 cell line with its redox/energy status: effects of curcumin and Khaya senegalensis.

OBJECTIVE: The fatality of cancer is mostly dependent on the possibility of occurrence of metastasis. Thus, if the development of metastasis can be prevented through novel therapeutic strategies targeted against this process, then the success of cancer treatment will drastically increase. In this study, therefore, we evaluated the antimetastatic potentials of an extract of Khaya senegalensis and curcumin on the metastatic liver cell line HepG2, and also assessed the anticancer property of the extract. METHODS: Cells were cultured and treated with graded concentrations of test substances for 24, 48, or 72 h with provisions made for negative controls. Treated cells were assessed as follows: nanotechnologically - atomic force microscopy (AFM) was used to determine cell stiffness; biochemically - cell cytotoxicity, glutathione level and adenosine triphosphate status, caspase activation and mitochondrial toxicity were considered; and microbiologically - a carrot disk assay was used to assess the anticancer property of the extract of K. senegalensis. RESULTS: Curcumin and K. senegalensis increased the cell stiffness by 2.6- and 4.0-fold respectively, indicating their antimetastatic effects. Corresponding changes in redox (glutathione level) and energy (adenosine triphosphate) status of the cells were also demonstrated. Further mechanistic studies indicated that curcumin was not mitotoxic in HepG2 cells unlike the K. senegalensis extract. In addition, the extract potently inhibited the Agrobacterium tumefaciens-induced genetic transformation based on carrot disk assay. CONCLUSION: Cell elasticity measurement data, using AFM, strongly suggested, for the first time, that both curcumin and the extract of K. senegalensis exhibited antimetastatic properties on HepG2 cells.

Modeling, Simulation, and Implementation of Solar-Driven Water-Splitting Devices.

An integrated cell for the solar-driven splitting of water consists of multiple functional components and couples various photoelectrochemical (PEC) processes at different length and time scales. The overall solar-to-hydrogen (STH) conversion efficiency of such a system depends on the performance and materials properties of the individual components as well as on the component integration, overall device architecture, and system operating conditions. This Review focuses on the modeling- and simulation-guided development and implementation of solar-driven water-splitting prototypes from a holistic viewpoint that explores the various interplays between the components. The underlying physics and interactions at the cell level is are reviewed and discussed, followed by an overview of the use of the cell model to provide target properties of materials and guide the design of a range of traditional and unique device architectures.

The SSTARS (STeroids and Stents Against Re-Stenosis) Trial: Different stent alloys and the use of peri-procedural oral corticosteroids to prevent in-segment restenosis after percutaneous coronary intervention.

BACKGROUND: Stent design and technological modifications to allow for anti-proliferative drug elution influence restenosis rates following percutaneous coronary intervention (PCI). We aimed to investigate whether peri-procedural administration of corticosteroids or the use of thinner strut cobalt alloy stents would reduce rates of binary angiographic restenosis (BAR) after PCI. METHODS: This was a two centre, mixed single and double blinded, randomised controlled trial using a factorial design. We compared (a) the use of prednisolone to placebo, starting at least six hours pre-PCI and continued for 28days post-PCI, and (b) cobalt chromium (CoCr) to stainless steel (SS) alloy stents, in patients admitted for PCI. The primary end-point was BAR at six months. RESULTS: 315 patients (359 lesions) were randomly assigned to either placebo (n=145) or prednisolone (n=170) and SS (n=160) or CoCr (n=160). The majority (58%) presented with an ACS, 11% had diabetes and 287 (91%) completed angiographic follow up. BAR occurred in 26 cases in the placebo group (19.7%) versus 31 cases in the prednisolone group (20.0%) respectively, p=1.00. For the comparison between SS and CoCr stents, BAR occurred in 32 patients (21.6%) versus 25 patients (18.0%) respectively, p=0.46. CONCLUSION: Our study showed that treating patients with a moderately high dose of prednisolone for 28days following PCI with BMS did not reduce the incidence of BAR. In addition, we showed no significant reduction in 6month restenosis rates with stents composed of CoCr alloy compared to SS (http://www.isrctn.com/ISRCTN05886349).

Genome-wide effects of selenium and translational uncoupling on transcription in the termite gut symbiont Treponema primitia.

UNLABELLED: When prokaryotic cells acquire mutations, encounter translation-inhibiting substances, or experience adverse environmental conditions that limit their ability to synthesize proteins, transcription can become uncoupled from translation. Such uncoupling is known to suppress transcription of protein-encoding genes in bacteria. Here we show that the trace element selenium controls transcription of the gene for the selenocysteine-utilizing enzyme formate dehydrogenase (fdhFSec) through a translation-coupled mechanism in the termite gut symbiont Treponema primitia, a member of the bacterial phylum Spirochaetes. We also evaluated changes in genome-wide transcriptional patterns caused by selenium limitation and by generally uncoupling translation from transcription via antibiotic-mediated inhibition of protein synthesis. We observed that inhibiting protein synthesis in T. primitia influences transcriptional patterns in unexpected ways. In addition to suppressing transcription of certain genes, the expected consequence of inhibiting protein synthesis, we found numerous examples in which transcription of genes and operons is truncated far downstream from putative promoters, is unchanged, or is even stimulated overall. These results indicate that gene regulation in bacteria allows for specific post-initiation transcriptional responses during periods of limited protein synthesis, which may depend both on translational coupling and on unclassified intrinsic elements of protein-encoding genes. IMPORTANCE: A large body of literature demonstrates that the coupling of transcription and translation is a general and essential method by which bacteria regulate gene expression levels. However, the potential role of noncanonical amino acids in regulating transcriptional output via translational control remains, for the most part, undefined. Furthermore, the genome-wide transcriptional state in response to translational decoupling is not well quantified. The results presented here suggest that the noncanonical amino acid selenocysteine is able to tune transcription of an important metabolic gene via translational coupling. Furthermore, a genome-wide analysis reveals that transcriptional decoupling produces a wide-ranging effect and that this effect is not uniform. These results exemplify how growth conditions that impact translational processivity can rapidly feed back on transcriptional productivity of prespecified groups of genes, providing bacteria with an efficient response to environmental changes.

Imagining the present: amnesia may impair descriptions of the present as well as of the future and the past.

Recent evidence suggests that in some patients with amnesia the capacity to imagine the future is impaired in parallel with the capacity to remember the past. This paper asks whether descriptions of the present may be similarly affected. We recruited 7 patients with amnesic syndromes of varying aetiologies who were matched for age, sex and education with 7 control participants. Patients showed no deficits on subjective measures of visual imagery. They were impaired by comparison with controls on measures of imagination and future thinking. However there was an even more marked impairment on tasks requiring them to give descriptions of their current experience. Potential explanations include effects of amnesia on narrative construction or on the texture of experience itself, and the confounding influence of cognitive impairments outside the memory domain. We conclude that tasks requiring descriptions of current experience provide a valuable control condition in studies examining the relationship between memory and imagination.

Genetic variation throughout the folate metabolic pathway influences negative symptom severity in schizophrenia.

Low serum folate levels previously have been associated with negative symptom risk in schizophrenia, as has the hypofunctional 677C>T variant of the MTHFR gene. This study examined whether other missense polymorphisms in folate-regulating enzymes, in concert with MTHFR, influence negative symptoms in schizophrenia, and whether total risk allele load interacts with serum folate status to further stratify negative symptom risk. Medicated outpatients with schizophrenia (n = 219), all of European origin and some included in a previous report, were rated with the Positive and Negative Syndrome Scale. A subset of 82 patients also underwent nonfasting serum folate testing. Patients were genotyped for the MTHFR 677C>T (rs1801133), MTHFR 1298A>C (rs1801131), MTR 2756A>G (rs1805087), MTRR 203A>G (rs1801394), FOLH1 484T>C (rs202676), RFC 80A>G (rs1051266), and COMT 675G>A (rs4680) polymorphisms. All genotypes were entered into a linear regression model to determine significant predictors of negative symptoms, and risk scores were calculated based on total risk allele dose. Four variants, MTHFR 677T, MTR 2756A, FOLH1 484C, and COMT 675A, emerged as significant independent predictors of negative symptom severity, accounting for significantly greater variance in negative symptoms than MTHFR 677C>T alone. Total allele dose across the 4 variants predicted negative symptom severity only among patients with low folate levels. These findings indicate that multiple genetic variants within the folate metabolic pathway contribute to negative symptoms of schizophrenia. A relationship between folate level and negative symptom severity among patients with greater genetic vulnerability is biologically plausible and suggests the utility of folate supplementation in these patients.

Loss of imagery phenomenology with intact visuo-spatial task performance: a case of 'blind imagination'.

The capacity for imagery, enabling us to visualise absent items and events, is a ubiquitous feature of our experience. This paper describes the case of a patient, MX, who abruptly lost the ability to generate visual images. He rated himself as experiencing almost no imagery on standard questionnaires, yet performed normally on standard tests of perception, visual imagery and visual memory. These unexpected findings were explored using functional MRI scanning (fMRI). Activation patterns while viewing famous faces were not significantly different between MX and controls, including expected activity in the fusiform gyrus. However, during attempted imagery, activation in MX's brain was significantly reduced in a network of posterior regions while activity in frontal regions was increased compared to controls. These findings are interpreted as suggesting that MX adopted a different cognitive strategy from controls when performing the imagery task. Evidence from experimental tasks thought to rely on mental imagery, such as the Brooks' matrices and mental rotation, support this interpretation. Taken together, these results indicate that successful performance in visual imagery and visual memory tasks can be dissociated from the phenomenal experience of visual imagery.

[Schnitzler syndrome--report on a fourteen-year course of the disease and an overview of information on the disease]. / Schnitzleruv syndrom--popis ctrnáctiletého prubehu nemoci a prehled informací o této nemoci.

Schnitzler syndrome is a rare disease characterised by chronic urticaria and the presence of monoclonal IgM immunoglobulin, and by other symptoms. We report ourexperience with 14-year treatment of a patient. The first medical examination in our workplace was at the beginning of 1995 and the patient was diagnosed with the disease in 1996 (at the age of 52). Antihistaminics, the first medication used to relieve the symptoms of urticaria, had no subjective or objective effect. After the detection of osteolytic-osteosclerotic changes in the pelvic region, in areas with intense pain, we started treatment with pamidronate (90 mg at 28-day intervals), and the pain disappeared completely within 3 months of application of the drug. When the bisphosphonate therapy was interrupted, the pain recurred and receded completely after renewal of bisphosphonate administration. After the diagnosis, we gave the patient high doses of dexametazone (40 mg day 1-4, 10-13 and 20-23, at 28-day cycles). However, the therapy suppressed urticaria only on the days dexametasone was administered and the effect did not last when the drug was discontinued. Therefore we moved to continuous daily doses of prednisone (10-30 mg, depending on the intensity of problems), which was the only therapy with a long-term effect which was relatively well tolerated at the same time. Based on the excellent effect of 2-chlordeoxyadenosine in Waldenström's macroglobulinaemia, three cycles of this therapy were administered to the patient in 1996 (0.1 mg/kg/day, 7 days, at 28-day intervals). After the first infusion, urticarious lesions disappeared, but the positive effect on skin eruptions was limited in time and lasted only 14 days after the last infusion, i.e. the medication proved ineffective from a long-term point of view. The first improvement lasting for a longer period of time (partial remission) was achieved by regular application of interferon alpha (3 QU 3 times a week). However, adverse effects of interferon alpha prevailed after two years and the therapy was discontinued. Similarly phototherapy using the PUVA method resulted in partial regression of urticarious symptoms. Subsequently tested cyclosporine A (5 mg/kg/day) brought no benefit. Thalidomide (100 mg in the evening) administered on a continuous basis relieved pruritus and improved sleep disturbed by pruritus. However, adverse effects prevailed after 4 months and the therapy had to be discontinued, too. In 2005, we were hoping to achieve positive results with the most effective treatment for multiple myeloma of the time, a combination of bortezomib (1.3 mg/m2 i.v. on day 1, 4, 8 and 11, thalidomide 100 mg daily and dexametazon 20 mg p.o. on days 1-4 and 8-11 in 21-day cycles --VTD). A total of 4 complete cycles and 4 cycles with bortezomib reduced by 50% were applied. Urticarious eruptions were reduced by at least 50% in the course of the therapy, and also the concentration of monoclonal immunoglobin decreased temporarily by more than 50%. However, after the therapy was discontinued, the symptoms returned with their original intensity, which means that VTD regime did not provide a long-term therapeutic response. In 2007, we started the anakinra (Kineret) therapy. Skin symptoms disappeared after the first injection and a dose of 100 mg/ day has kept the patient free of skin symptoms for 12 months by now. Also the CRP value which had been constantly high returned to normal, and haemoglobin values increased to achieve physiological range. In the course of 14 years, we confirmed partial therapeutic effect of glucocorticoids administered on a continuous basis, as well as a partial therapeutic effect of interferon alpha, thalidomide and PUVA, but all the therapies had to be discontinued due to adverse effects. A major turn, i.e. the complete disappearance of skin symptoms and normalisation of CRP and haemoglobin values, only came with anakinra which has become the drug of the first choice for the above syndrome.

ATP-dependent association between subunits of Clp protease in pea chloroplasts.

The chloroplast ATP-dependent Clp protease (EC 3.4.21.92) is composed of the proteolytic subunit ClpP and the regulatory ATPase, ClpC. Although both subunits are found in the stroma, the interaction between the two is dynamic. When immunoprecipitation with antibodies against ClpC was performed on stroma from dark-adapted pea (Pisum sativum L. cv. Alaska) chloroplasts, ClpC but not ClpP was precipitated. However, when stroma was supplemented with ATP, both ClpC and ClpP were precipitated. Co-immunoprecipitation was even more efficient in the presence of ATP-gamma-S, suggesting that the association between regulatory and proteolytic subunits is dependent on binding of ATP to ClpC, but not its hydrolysis. To further test this association, stroma was fractionated by column chromatography, and the presence of Clp subunits in the different fractions was monitored immunologically. When stroma depleted of ATP was fractionated on an ion-exchange column, ClpP and ClpC migrated separately, whereas in the presence of ATP-gamma-S both subunits co-migrated. Similar results were observed in size-exclusion chromatography. To further characterize the precipitated enzyme, its proteolytic activity was assayed by testing its ability to degrade beta-casein. No degradation was observed in the absence of ATP, and degradation was inhibited in the presence of phenylmethylsulfonyl fluoride, consistent with Clp being an ATP-dependent serine protease. The activity of the isolated enzyme was further tested using chimeric OE33 as a model substrate. This protein was also degraded in an ATP-dependent manner, supporting the suggested role of Clp protease as a major housekeeping protease in the stroma.

[Detection of myeloma cells in peripheral blood using multi-parameter flow cytometry: monitoring residual disease]. / Detekce myelomových bunek v periferní krvi vícerozmernou prutokovou cytometrií: monitorování zbytkové nemoci.

BACKGROUND: The aim of this study was to evaluate significance of CD 38(+2)45-54+, CD 38(+2)45-56+ and CD 38(+2)45-138+ cells counts in peripheral blood of patients with multiple myeloma for monitoring of the minimal residual disease. METHODS AND RESULTS: A triple-color flow cytometric analysis was used for this purpose. Peripheral blood of 29 patients with multiple myeloma who underwent high dose chemotherapy and autologous stem cells transplantation was repeatedly analysed. Counts of myeloma cells in peripheral blood were compared to serum monoclonal immunoglobulin concentration, serum calcium level, serum C-reactive protein, serum beta 2 microglobulin, and number of myeloma cells in bone marrow (morphology). From 29 patients in this study, 5 patients have relapsed. Patients in relapse had significantly higher counts of CD 38(+2)45-54+, CD 38(+2)45-56+ and CD 38(+2)45-138+ cells in peripheral blood than patients in remission (geometrical average: 12.41; 6.20; 14.45 cells/microliter versus 4.08; 2.87; 2.58 cells/microliter). The number of these cells correlated well with serum monoclonal immunoglobulin level and counts of myeloma cells in bone marrow. CONCLUSION: The authors conclude that the longitudinal multi-color flow cytometric analysis of CD 38(+2)45-54+, CD 38(+2)45-56+ and CD 38(+2)45-138+ cells in peripheral blood of patients with multiple myeloma is a useful method for evaluation of the disease activity. Significance of peripheral myeloma cells count for prediction of the relapse of the multiple myeloma remains to be evaluated.

Molecular cloning of a carotenoid-associated protein from Cucumis sativus corollas: homologous genes involved in carotenoid sequestration in chromoplasts.

Chromoplasts are carotenoid-accumulating plastids found in the corollas and fruits of many higher plants. In most cases, the pigment in these plastids is accumulated with the aid of carotenoid-associated proteins located within unique structures. This paper reports the isolation and characterization of the cDNA (CHRC) from Cucumis sativus corollas which encodes the chromoplast-specific carotenoid-associated protein CHRC. The transit peptide cleavage site was determined and, using a chloroplast uptake system, it is shown that CHRC can be post-translationally targeted to these plastids where it is peripherally associated with thylakoids. Analysis of CHRC transcript level in Cucumis sativus revealed its temporal and tissue-specific regulation: the transcript was detected only in corollas, where its level increased in parallel to flower development, peaking just before anthesis. CHRC shares significant homology (59%) with the gene coding for fibrillin-a protein in Capsicum annuum red fruits whose function is essentially identical to that of CHRC. A CHRC fragment including the potential active site of the protein was used as a probe in Northern blot analyses of floral and fruit tissues from various plants containing chromoplasts of different types: CHRC homologs of similar sizes were revealed in all cases. The existence of a group of homologous genes coding for chromoplast-specific proteins which aid in the sequestration of carotenoids within specific structures is proposed.

Biogenesis of a photosystem I light-harvesting complex. Evidence for a membrane intermediate.

CAB-7p is a chlorophyll a/b binding protein of photosystem I (PSI). It is found in light-harvesting complex I 680 (LHCI-680), one of the chlorophyll complexes produced by detergent solubilization of PSI. Two types of evidence are presented to indicate that assembly of CAB-7p into PSI proceeds through a membrane intermediate. First, when CAB-7p is briefly imported into chloroplasts or isolated thylakoids, we initially observe a fast-migrating membrane form of CAB-7p that is subsequently converted into PSI. The conversion of the fast-migrating form into PSI does not require stroma or ATP. Second, trypsin treatment of thylakoids containing radiolabeled CAB-7p indicates that there are at least two membrane forms of the mature 23-kD protein. The predominant form is completely resistant to proteolysis; a second form of the protein is cleaved by trypsin into 12- and 7-kD polypeptides. We interpret this to mean that the intermediate is a cleavable form that becomes protease resistant during assembly. This notion is supported by the observation that CAB-7p in LHCI-680 is largely cleaved by trypsin into 12- and 7-kD polypeptides, whereas CAB-7p in isolated PSI particles is trypsin resistant. In vitro, we generated a mutant form of CAB-7p, CAB-7/BgI2p, that was able to integrate into thylakoid membranes but was unable to assemble into PSI. The membrane form of CAB-7/BgI2p, like LHCI-680, was predominantly cleaved by trypsin into 12- and 7-kD fragments. We suggest that the mutant protein is arrested at an intermediate stage in the assembly pathway of PSI. Based on its mobility in nondenaturing gels and its susceptibility to protease cleavage, we suggest that the intermediate form is LHCI-680. We propose the following distinct stages in the biogenesis of LHCI: (a) apoprotein is integrated into the thylakoid, (b) chlorophyll is rapidly bound to apoprotein forming LHCI-680, and (c) LHCI-680 assembles into the native PSI complex.

[Monitoring of arterial pressure according to the "womb to tomb" program taking into account the human chronome]. / Monitorirovanie arterial'nogo davleniia po programme "ot rozhdeniia do smerti" s uchetom khronoma u cheloveka.

The concept of "chronome" is discussed in this article. A lot of data of monitoring of arterial blood pressure in healthy people from babies till senile people are reported. This chronobiologic approach allows to optimize diagnosis in a group of people with elevated blood pressure and to exclude people with false positive and false negative diagnosis of hypertension. At the same time physicians can optimize therapy of hypertensive people with taking into account chronotherapy principle.