(C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“A rapid, sensitive loop-mediated isothermal amplification (LAMP) assay was established for diagnosis of bovine leukemia virus (BLV) infection. The LAMP assay for targeting the BLV-LTR region can detect at least 2 copies of proviral DNA in a 2 mu l sample and its sensitivity is equivalent to or greater than the conventional single PCR. In addition, amplification

is obtained in less than 1 h by incubating a single tube in a water bath. The data obtained LEE011 in vivo by the LAMP assay applied to field samples were compared with PCR and serological tests for BLV. The results showed a high level of agreement with these serological methods, but there was one animal positive only by the LAMP assay. When the blood was collected from the cow after 6 months, the BLV antibody was detected. This Suggested that the LAMP assay Could help the detection of the cattle in the early stage of BLV infection. The LAMP assay is a rapid, sensitive and simple method for the diagnosis of BLV infection

as reported for other pathogens, and is available for use in local laboratories without any special equipment. (C) 2008 Elsevier B.V. All rights reserved.”
“Parkinson’s disease (PD) is a neurodegenerative disease of the central nervous system and its prevalence increases with age. Microtubule-associated protein tau (MAPT), a neuronal protein is involved in the pathogenesis of several neurodegenerative selleck chemicals llc diseases including PD. To determine the ABT-737 cell line broader significance of this association with PD, replicative studies in distinct ethnic populations are required. In this study, we investigated MAPT for its potential association with PD using five haplotype-tagging SNPs and the del-In9 polymorphism of MAPT in 301 PD patients and 243 healthy controls from eastern India. Our case-control analysis did not show a significant association

with any of the markers and PD. However, a risk haplotype [GAC + G] for PD was identified (OR 1.563; 95% CI = 1.045-2.337; p = 0.03). In addition, haplotype AAC + A (OR = 2.787; 95% Cl = 1.372-5.655; p = 0.004) was strongly associated with early onset PD (age at onset <= 40 years) and AAC + G haplotype showed a weak association (OR = 2.233; 95% Cl = 1.018-4.895; p = 0.045) with late onset PD (age at onset >40 years). This observation highlights the significance of rs7521 in modifying the age at onset of PD under a common haplotype background. We also identified AGC+A as a risk haplotype for sporadic cases (OR = 2.773,95% Cl = 1.198-6.407, p = 0.016). This is the first association study from India conducted on MAPT among PD patients and provides valuable information for comparison with other ethnic groups. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“Human cytomegalovirus (HCMV) is an opportunistic human pathogen that causes serious clinical illness in immunocompromised individuals.

9 mmol/L potassium) adenosine-lidocaine group increased coronary vascular resistance by only 30% and spontaneously recovered 107% heart rate, 92% systolic pressure, 81% aortic flow, and 113% coronary flow (all metrics returned 85% to 100% at 15 minutes) with no reperfusion arrhythmias. In contrast, hearts in the adenosine-lidocaine (3, 10, and 16 mmol/ L potassium)

groups were all PD0332991 manufacturer slow to recover (15% to 40% return at 15 minutes) and experienced arrhythmias. Increasing potassium levels in adenosine-lidocaine cardioplegia from 5.9 to 16 mmol/L resulted in a 67% loss of left ventricular contractility.

Conclusions: Polarizing adenosine-lidocaine cardioplegia (5.9 mmol/ L potassium) administered intermittently at 33 degrees C provides superior arrest and reanimation profiles under normokalemic conditions when the myocardial cell membrane potential

is close to its resting state. (J Thorac Cardiovasc Surg 2010;139:1576-86)”
“Russia, Ukraine and Kazakhstan are the leading agricultural producers, especially for potato, sugar beet and sunflower. The cumulative effect of adverse climatic XAV-939 purchase conditions, high weediness and losses related to viruses and pests (without any insecticide and herbicide treatments) led to losses amounting to 40-80% of potential production in the Russian Federation and other mentioned countries. We have used new biotechnology methods to obtain several crops (potato, sugar beet, sunflower and others) tolerant to abiotic and biotic stresses. For the first time – on the basis of domestic varieties bred by Russian scientists – GM potato varieties have been obtained, resistant to Colorado beetle. These GM potato varieties were recognised as being as safe as traditional ones and have been registered for food use. Using this technology, new biotechnological sugar beet lines Cyclosporin A tolerant to herbicides were also obtained.”
“Objective: Osteopontin is a multifunctional phosphoprotein

with an important but poorly understood role in non-small cell lung cancer pathogenesis. We hypothesize that osteopontin isoforms (OPNa, OPNb, and OPNc) have divergent roles in non-small-cell lung cancer angiogenesis and divergent impact on vascular endothelial growth factor secretion.

Methods: We examined mRNA expression using reverse transcriptase-polymerase chain reaction primers for 3 osteopontin isoforms in non-small-cell lung cancer and immortalized bronchial epithelial cell lines, and correlated expression with osteopontin secretion into media detected by enzyme-linked immunosorbent assay. Angiogenic properties conferred by osteopontin isoforms were evaluated by transfecting cDNA plasmids specific to each isoform and controls into non-small-cell lung cancer cell lines, H153 and H358 (low endogenous osteopontin) and A549 and H460 (high endogenous osteopontin), analyzing conditioned media on a bovine capillary endothelial platform, and measuring vascular endothelial growth factor levels by enzyme-linked immunosorbent assay.

We then specify definitions

that maximise international comparability. Even with this optimisation of data usage, only seven of the 25 indicators, covered at least 50% of the world’s adolescents. The worst adolescent health profiles are in sub-Saharan Dinaciclib Africa, with persisting high mortality from maternal and infectious causes. Risks for non-communicable diseases are spreading rapidly, with the highest rates of tobacco use and overweight, and lowest rates of physical activity, predominantly in adolescents living in low-income and middle-income countries. Even for present global health agendas, such as HIV infection and maternal mortality, data sources are incomplete for adolescents. We propose a series of steps that include better coordination and use of data collected across countries, greater harmonisation of school-based surveys, further development of strategies for socially marginalised youth, targeted research into the validity

and use of these health indicators, advocating for adolescent-health information within new global health initiatives, and a recommendation that every country produce a regular report on the health of its adolescents.”
“Agomelatine is a melatonergic MT1/MT2 agonist and a serotonin (5-HT) 5-HT2C antagonist. The effects of 2-day and 14-day administration of agomelatine were investigated on the activity of ventral tegmental area (VTA) dopamine (DA), locus coeruleus (LC) norepinephrine (NE), and dorsal raphe nucleus (DRN) 5-HT neurons using in vivo electrophysiology in rats. The 5-HT1A transmission was assessed at hippocampus CA3 pyramidal neurons. Dorsomorphin cell line After a 2-day regimen of agomelatine (40 mg/kg/day, i.p.), an increase in the number of spontaneously active VTA-DA neurons (p < 0.001) and in the firing rate of LC-NE neurons (p < 0.001) was observed. After 14 days, the administration of agomelatine induced an increase in: (1) the number of spontaneously active DA neurons (p < 0.05), (2) the Sitaxentan bursting activity of DA neurons (bursts/min, p < 0.01 and percentage of spikes

occurring in bursts, p < 0.05), (3) the firing rate of DRN-5-HT neurons (p < 0.05), and (4) the tonic activation of postsynaptic 5-HT1A receptors located in the hippocampus. The increase in 5-HT firing rate was D2 dependent, as it was antagonized by the D2 receptor antagonist paliperidone. The enhancement of NE firing was restored by the 5-HT2A receptor antagonist MDL-100,907 after the 14-day regimen. All the effects of agomelatine were antagonized by a single administration of the melatonergic antagonist S22153 (except for the increase in the percentage of spikes occurring in burst for DA neurons). The present results suggest that (1) agomelatine exerts direct (2 days) and indirect (14 days) modulations of monoaminergic neuronal activity and (2) the melatonergic agonistic activity of agomelatine contributes to the enhancement of DA and 5-HT neurotransmission. Neuropsychopharmacology (2013) 38, 275-284; doi:10.1038/npp.2012.

(C) 2010 Elsevier BM. All rights reserved.”
“Background

Idiopathic pulmonary fibrosis is a progressive lung disease

with a high mortality rate. Because the signaling pathways activated by several tyrosine kinase receptors have been shown to be involved in lung fibrosis, it has been suggested that the inhibition of these receptors may slow the progression of idiopathic pulmonary fibrosis.

Methods

In a 12-month, phase 2 trial, we assessed the efficacy and safety of four different oral doses of the tyrosine kinase inhibitor BIBF 1120 as compared with placebo in patients with idiopathic pulmonary fibrosis. The primary end 8-Bromo-cAMP molecular weight point was the annual rate of decline selleck in forced vital capacity (FVC). Secondary end points included acute exacerbations, quality of life (measured with the St. George’s Respiratory Questionnaire [SGRQ]), and total lung capacity.

Results

A total of 432 patients underwent randomization

to receive one of four doses of BIBF 1120 (50 mg once a day, 50 mg twice a day, 100 mg twice a day, or 150 mg twice a day) or placebo. In the group receiving 150 mg of BIBF 1120 twice a day, FVC declined by 0.06 liters per year, as compared with 0.19 liters per year in the placebo group, a 68.4% reduction in the rate of loss with BIBF 1120 (P=0.06 with the closed testing procedure for multiplicity correction;

P=0.01 with the hierarchical testing procedure). This dose also resulted in a lower incidence of acute exacerbations, as compared with placebo (2.4 vs. 15.7 per 100 patient-years, P=0.02) and a small decrease in the SGRQ score (assessed on a scale of 0 to 100, with lower scores indicating better quality of life) as compared with an increase with placebo (-0.66 vs. 5.46, P=0.007). Gastrointestinal symptoms (which led to more discontinuations in the group receiving 150 mg twice a day than in the placebo group) and increases in levels of liver aminotransferases were more frequent in the group receiving 150 mg of BIBF 1120 twice daily than in the placebo group.

Conclusions

In patients with idiopathic pulmonary fibrosis, BIBF 1120 at a dose GSK461364 in vivo of 150 mg twice daily, as compared with placebo, was associated with a trend toward a reduction in the decline in lung function, with fewer acute exacerbations and preserved quality of life. (Funded by Boehringer Ingelheim; ClinicalTrials. gov number, NCT00514683.)”
“Commercial enzyme-linked immunosorbent assay (ELISA) kits for the determination of the in vitro potency of recombinant hepatitis B vaccines, which detect hepatitis B surface antigen (HBsAg), have been used frequently as an alternative for traditional in vivo potency tests.

3-9.3), and upgrading plus up staging (HR 6.9, 95% Cl 3.3-14.5) were associated with a higher risk

of biochemical recurrence in patients who met University of California-San Francisco criteria.

Conclusions: Men who met enrollment Nec-1s molecular weight criteria for the 2 active surveillance protocols had a similar rate of upgrading, up staging and 5-year biochemical recurrence-free rates after radical prostatectomy. Further comparison between current protocols is warranted to establish universal inclusion criteria.”
“(R)-roscovitine (Ros) is a cyclin-dependent kinase inhibitor that also has been shown to have direct agonist and antagonist actions on Ca(v)2.1 (P/Q-type) and Ca(v) 2.2 (N-type) families of voltage-gated calcium channels. These kinase-independent effects represent a novel opportunity to advance our understanding of calcium channel function and

calcium-triggered neurotransmitter release. Furthermore, such actions on calcium channels may direct the development of Ros derivatives as new therapeutic agents. We used patch clamp recordings to characterize mechanisms that underlie the agonist effects of Ros on unitary N-type calcium channel gating. We found that N-type channels normally selleck compound gate with either a short or long mean open time, that Ros significantly prolonged the mean open time of the long gating component and increased the probability of observing channels that gated with a long open time, but had no effect on single channel conductance. Using Monte Carlo simulations of a single channel kinetic model and Ros interactions, we were able to reproduce our experimental results and investigate the model’s microscopic dynamics. In particular, our simulations predicted that the longer open times generated by Ros were due to the appearance of a long open state combined with an increased amount of time spent in transitions between open states. Our results suggest a mechanism for agonist effects of Ros at the level of single channels, and provide a mechanistic explanation MAPK inhibitor for previously reported agonist effects on whole cell calcium currents. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Purpose: Positive

surgical margins have a negative impact on disease outcomes after radical prostatectomy, yet their prognostic value may vary depending on specific pathological characteristics. We examined the relationship of positive surgical margins to biochemical progression according to several clinicopathological features.

Materials and Methods: We analyzed data from 1,268 patients who underwent radical prostatectomy for clinically localized prostate cancer at our center between 1992 and 2008, and did not receive any neoadjuvant or adjuvant treatment. We examined the relation of age, pretreatment prostate specific antigen, pathological T stage, radical prostatectomy Gleason score, disease risk group and surgical margin status to biochemical progression-free survival.

Results: The overall positive surgical margin rate was 20.

This approach could also be useful in the design of lentiviral vectors that transduce these relatively resistant cells.”
“Patterned

regular sieves and filters with comparable molecular dimensions hold great promise as an alternative to conventional polymeric gels and fibrous membranes to improve biomolecule separation. Recent developments of microfabricated nanofluidic sieves and filters have demonstrated superior performance for both analytical and preparative separation of various physiologically relevant macromolecules, including proteins. The insights gained from designing these artificial molecular sieves and filters, along with the promising results gathered GW4064 in vivo from their first applications, serve to illustrate the impact that they can have on improving future separation of complex biological samples. Further development of artificial sieves and filters with more elaborate geometrical constraints and tailored surface functionality is believed to provide more promising ideals and results for biomolecule separation, which has great implications for proteomic research and biomarker discovery.”
“Iron accumulation in the brain has been associated to the pathogenesis of neurodegenerative disorders. We have previously demonstrated that iron overload in the neonatal period results in severe and persistent memory deficits in

adult rats. Alterations in histone acetylation have been associated with memory deficits Liproxstatin-1 purchase in models of neurological disorders. Here we examine histone acetylation in the brain and the effects of the histone deacetylase inhibitor (HDACi) www.selleckchem.com/products/kpt-330.html sodium butyrate (NaB) on memory in the neonatal iron overload model in rats. Rats received vehicle or 30.0-mg/kg Fe(+2) orally at postnatal days 12-14. When animals reached adulthood,

they were given training in either novel object recognition or inhibitory avoidance. Histone acetylation in the dorsal hippocampus and the effects of NaB were examined in separate sets of rats. Iron overload led to a reduction in H3 lysine 9 acetylation in the hippocampus, without affecting the acetylation of other H3 and H4 lysine residues. A single systemic injection of NaB (1.2 g/kg) immediately after training ameliorated iron-induced memory impairments. The results suggest that a reduction in H3K9 acetylation might play a role in iron-induced memory impairment and support the view that HDACis can rescue memory dysfunction in models of brain disorders. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Gene mutations and reassortment are key mechanisms by which influenza A virus acquires virulence factors. To evaluate the role of the viral polymerase replication machinery in producing virulent pandemic (H1N1) 2009 influenza viruses, we generated various polymerase point mutants (PB2, 627K/701N; PB1, expression of PB1-F2 protein; and PA, 97I) and reassortant viruses with various sources of influenza viruses by reverse genetics.

Acquisition of the Rigosertib manufacturer 60-nucleotide duplication appeared to have improved the fitness of this virus, and more recent subtype B strains may need to be included in experimental vaccines to evaluate their efficacy in the current setting of evolved circulating strains.”
“We report an experiment using event-related potentials (ERPs) to study selection by color uncontaminated from selection by location. Participants monitored an RSVP sequence for a given target letter that could appear in upper- or lowercase. Prior to the sequence, a cue indicated the most likely color

of the target letter. Replicating E. Vierck and J. Miller (2005), upper-/lowercase discrimination accuracy was higher following valid than invalid color cues. Within the ERPs, the target onset produced a negative component between 150 and 350 ms at occipital sites, with shorter latencies following valid than invalid cues. We also found larger amplitude components for valid than invalid color cues at central and parietal sites between 150 and 325 ms. The results not only demonstrate clear effects of color cuing on both behavior

and ERPs but also suggest that the observed ERP differences between valid versus invalid trials mediate the behavioral effects.”
“Many psychological and physiological studies with simple stimuli have suggested that perceptual learning specifically enhances the response of primary sensory cortex www.selleckchem.com/products/mrt67307.html to task-relevant stimuli. The aim of this study was to determine see more whether auditory discrimination training on complex tasks enhances primary auditory cortex responses to a target sequence relative to non-target and novel sequences.

We collected responses from more than 2000 sites in 31 rats trained on one of six discrimination tasks that differed primarily in the similarity of the target and distractor sequences. Unlike training with simple stimuli, long-term training with complex stimuli did not generate target-specific enhancement in any of the groups. Instead, cortical receptive field size decreased, latency decreased, and paired pulse depression decreased in rats trained on the tasks of intermediate difficulty, whereas tasks that were too easy or too difficult either did not alter or degraded cortical responses. These results suggest an inverted-U function relating neural plasticity and task difficulty. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.”
“gamma delta T cells comprise an evolutionarily conserved yet poorly understood subset of T cells. Numerous features place these unconventional lymphocytes at the branching point between antigen-presenting cells and natural killer cells of the innate immune system and major-histocompatibility-complex-restricted alpha beta T cells of the adaptive immune system. We propose a role for human V gamma 9/V delta 2 T cells in the generation of monocyte-derived inflammatory dendritic cells during infection.

1038/ki.2009.434; published online 18 November 2009″
“Near-infrared light therapy is an emerging neurostimulation technology, but its cellular mechanism of action remains unresolved. Using standard intracellular recording techniques, we observed that 5-10ms pulses of 1889 nm light depolarized the membrane MLN2238 ic50 potential for hundreds of milliseconds in more than 85% of dorsal root ganglion and nodose ganglion neurons tested. The laser-evoked depolarizations (LEDs) exhibited complex, multiphasic kinetics comprising fast and slow components. There was no discernable difference in the LEDs in intact ganglion neurons and in acutely isolated neurons. Thus, the LED sensor seems to reside within the neuronal membrane. The near-uniform

distribution of responsive neurons increased membrane conductance, and the negative reversal potential value (-41 +/- 2.9 mV) suggests that LED is unrelated to the activation of heat-sensitive transient receptor potential cation channel subfamily V member 1 channels. The long duration of LEDs favors an involvement of second messengers. NeuroReport 21: 662-666 (C) 2010 Wolters https://www.selleckchem.com/products/OSI027.html Kluwer Health | Lippincott Williams & Wilkins.”
“Although fibroblast growth factor 23 (FGF23) acting through its receptor Klotho-FGFR1c decreases parathyroid hormone expression, this hormone is increased in chronic kidney

disease despite an elevated serum FGF23. We measured possible factors that might contribute to the resistance of parathyroid glands to FGF23 in rats with the dietary adenine-induced model of chronic kidney disease. Quantitative immunohistochemical and reverse transcription-PCR analysis using laser capture microscopy showed that both Klotho and FGFR1 protein and mRNA levels were decreased in histological sections of the parathyroid glands. Recombinant FGF23 failed to decrease serum parathyroid hormone levels or activate the mitogen-activated protein kinase signaling pathway in the glands of rats with advanced experimental chronic kidney disease. In parathyroid

gland organ culture, the addition of FGF23 decreased parathyroid hormone secretion VE-822 research buy and mRNA levels in control animals or rats with early but not advanced chronic kidney disease. Our results show that because of a downregulation of the Klotho-FGFR1c receptor complex, an increase of circulating FGF23 does not decrease parathyroid hormone levels in established chronic kidney disease. This in vivo resistance is sustained in parathyroid organ culture in vitro. Kidney International (2010) 77, 211-218; doi:10.1038/ki.2009.464; published online 16 December 2009″
“Dopamine signaling is strongly implicated in the etiology of schizophrenia (SZ). Because of the essential role dopamine D2 receptor (DRD2) in dopamine signaling, DRD2 gene has been regarded as one of the top candidate genes for SZ. However, the findings from linkage and association analyses on this gene are mixed and largely inconsistent across various studies.

Conclusions: Sacral nerve stimulation is effective in the majority of our patients, and should be considered in children with severe dysfunctional elimination syndrome refractory to maximum medical treatment.”
“Purpose: We investigated the correlations between ultrasonographic bladder wall thickness and urodynamic parameters, and estimated

the diagnostic accuracy of bladder wall thickness for predicting unfavorable urodynamic patterns in children with myelodysplasia.

Materials and Methods: A total of 57 children (median age 5.1 years.) with myelodysplasia were enrolled in the study. All children underwent ultrasonography to measure bladder wall thickness. Videourodynamic evaluation was also performed within 3 months of ultrasound assessment. SRT1720 Bladder wall thickness was compared to urodynamic data. A urodynamic risk of upper urinary tract deterioration was defined as maximum detrusor pressure greater than 40 cm H2O during filling or at leakage, or sphincter dyssynergia during voiding.

Results: Bladder wall thickness was significantly correlated to detrusor leak point pressure, maximum amplitude of detrusor overactivity and maximum detrusor pressure during storage phase. In 16 children who had unfavorable urodynamic risk patterns the mean bladder wall thickness was 3.9 +/- 1.0 mm, compared to 2.4 +/- 0.7 mm. in 41 patients with favorable urodynamic patterns. There was a significant difference

between bladder wall thickness in children with and those without urodynamic risk factors Foretinib (p < 0.001). For a diagnosis INCB018424 cell line of unfavorable urodynamic patterns bladder wall thickness greater than 3.3 mm had a positive predictive value of 85.7%, a negative predictive value of 90.7%, specificity of 75.0% and sensitivity of 95.1%. Receiver operator characteristic analysis revealed that bladder wall

thickness had a high predictive value for unfavorable urodynamic patterns, with an area under the curve of 0.908.

Conclusions: Ultrasonographic assessment of bladder wall thickness is a sensitive screening tool for the diagnosis of urodynamic risk factors for upper urinary tract deterioration in children with myelodysplasia.”
“Purpose: Incidentally detected complex renal cysts in children are a rare but worrisome occurrence due to the perceived potential risk of malignancy. We examined the natural history of such cysts in a cohort of children.

Materials and Methods: We obtained access to a database containing all radiology reports generated at a single institution from 1996 to 2004. We used key words to limit our search, subsequently reviewing charts and images to confirm the diagnosis of a complex renal cyst and to collect clinical data. Cases were categorized according to a modification of the Bosniak classification, using ultrasound in most patients and computerized tomography or magnetic resonance imaging when available.

Results: Complex renal cysts were identified in 39 children.

The sickle cell trait genotype frequencies were 8.7% in non-diabetic ESRD, 7.1% in type 2 diabetes-ESRD, and 7.2% in controls. There was no age-, gender-, and admixture-adjusted significance for sickle cell trait association with non-diabetic

ESRD (odds ratio 1.16); type 2 diabetes-ESRD (odds ratio 1.01); or all-cause ESRD (combined non-diabetic and type 2 diabetic-ESRD patients compared to the controls; odds ratio 1.05) in dominant models. In addition, no evidence of APOL1 or MYH9 interactions with sickle cell trait was detected. Hence, sickle cell trait is not selleck kinase inhibitor associated with diabetic or non-diabetic ESRD in a large sample of African Americans.”
“Attention selects objects/groups as the most fundamental units, and this may be achieved by an attention-spreading mechanism. Previous event-related potential (ERP) studies have found that attention-spreading is reflected by a decrease in the N1 spatial attention effect. The present study tested whether the electrophysiological attention effect is associated with the perception of object unity or amodal completion through the use of partly-occluded objects. ERPs were recorded in 14 participants who were required to pay attention to their left or right visual field and to press a button for a target shape in the attended field. Bilateral stimuli were

presented rapidly, and were separated, connected, or connected behind an occluder. Behavioral performance in the connected this website and occluded conditions was worse than that in the separated condition, indicating that attention spread over perceptual object representations after amodal

completion. Consistently, the late N1 spatial attention effect (180-220 ms post-stimulus) and the early phase (230-280 ms) of feature selection effects (target N2) at contralateral sites decreased, equally for the occluded and connected conditions, while the attention effect see more in the early N1 latency (140-180 ms) shifted most positively for the occluded condition. These results suggest that perceptual organization processes for object recognition transiently modulate spatial and feature selection processes in the visual cortex. (C) 2012 Elsevier Ltd. All rights reserved.”
“Theoretical, desirable features of second-generation metal-on-metal (MoM) hip prostheses have led to their widespread use. However, the bearing surfaces, consisting of complex cobalt-chromium alloys, are subject to wear and the release of cobalt and chromium (CoCr) nanoparticles. These nanoparticles can reduce cellular viability, induce DNA damage, lead to chromosomal aberrations, and possibly stimulate increased metal hypersensitivity. Clinically, the effects can be both local (soft-tissue reactions) and systemic (arthroprosthetic cobaltism).