0 mmol/L within 7 days of a high level has also significantly inc

0 mmol/L within 7 days of a high level has also significantly increased (p < 0.0001). Further research into the long term toxic effects of

high lithium levels specifically the duration of the high level and the magnitude is on-going. These results do however suggest that an actively managed database for lithium aids more effective monitoring of lithium and by improving the response times to high levels reduces patient exposure to the potentially toxic effects of lithium levels >1.0 mmol/L. A major limitation of this research is that other external factors impacting on the re-test rates and times to next level <1.0 mmol/L could not be controlled. The reasons for the high levels and the actions taken by the clinical team are not known from the information on the database. 1. NICE. National Institute for Clinical Excellence. Bipolar disorder: The management AP24534 of bipolar disorder in adults, children and adolescents, in primary and secondary care. Clinical Guideline 38 2006. 2006. Sally Jacobs, Karen Hassell, Sheena Johnson University of Manchester, Manchester,

UK This review identified and synthesised existing evidence for the effectiveness of organisational interventions designed to prevent or manage workplace stress. A range of interventions was identified demonstrating benefits for both employees and organisations and a model derived of BIBW2992 datasheet best practice. These findings constitute a good starting point for community pharmacies seeking to develop effective organisational

solutions to workplace stress. Workplace stress is a current concern amongst community pharmacists.1 The response of community pharmacies to perceived increases in workplace pressures could be instrumental in ensuring that they do not adversely affect pharmacists’ wellbeing or lead to an increase in dispensing errors. Yet no evidence exists of cost-effective solutions to workplace stress in community pharmacy settings. As part of a scoping study, a review of the wider organisational literature was conducted to identify effective organisational clonidine interventions for preventing or managing workplace stress. This review did not require ethical approval. A secondary synthesis of existing reviews (1995–2010) from peer-reviewed and professional sources was conducted. Reviews were identified through existing knowledge and keyword searching of the internet and electronic databases (OVID: Medline, Cinahl, HMIC; CSA: social science databases, ABI Inform). Search terms included those relating to work stress, intervention studies, and review papers. Inclusion/exclusion criteria limited the scope of the review and guided the identification and selection of papers. Crucially, only reviews of interventions including an organisational element (i.e.

0 mmol/L within 7 days of a high level has also significantly inc

0 mmol/L within 7 days of a high level has also significantly increased (p < 0.0001). Further research into the long term toxic effects of

high lithium levels specifically the duration of the high level and the magnitude is on-going. These results do however suggest that an actively managed database for lithium aids more effective monitoring of lithium and by improving the response times to high levels reduces patient exposure to the potentially toxic effects of lithium levels >1.0 mmol/L. A major limitation of this research is that other external factors impacting on the re-test rates and times to next level <1.0 mmol/L could not be controlled. The reasons for the high levels and the actions taken by the clinical team are not known from the information on the database. 1. NICE. National Institute for Clinical Excellence. Bipolar disorder: The management Cyclopamine price of bipolar disorder in adults, children and adolescents, in primary and secondary care. Clinical Guideline 38 2006. 2006. Sally Jacobs, Karen Hassell, Sheena Johnson University of Manchester, Manchester,

UK This review identified and synthesised existing evidence for the effectiveness of organisational interventions designed to prevent or manage workplace stress. A range of interventions was identified demonstrating benefits for both employees and organisations and a model derived of Panobinostat ic50 best practice. These findings constitute a good starting point for community pharmacies seeking to develop effective organisational

solutions to workplace stress. Workplace stress is a current concern amongst community pharmacists.1 The response of community pharmacies to perceived increases in workplace pressures could be instrumental in ensuring that they do not adversely affect pharmacists’ wellbeing or lead to an increase in dispensing errors. Yet no evidence exists of cost-effective solutions to workplace stress in community pharmacy settings. As part of a scoping study, a review of the wider organisational literature was conducted to identify effective organisational Y-27632 2HCl interventions for preventing or managing workplace stress. This review did not require ethical approval. A secondary synthesis of existing reviews (1995–2010) from peer-reviewed and professional sources was conducted. Reviews were identified through existing knowledge and keyword searching of the internet and electronic databases (OVID: Medline, Cinahl, HMIC; CSA: social science databases, ABI Inform). Search terms included those relating to work stress, intervention studies, and review papers. Inclusion/exclusion criteria limited the scope of the review and guided the identification and selection of papers. Crucially, only reviews of interventions including an organisational element (i.e.

Association of RMSD with variables was determined using Chi-squar

Association of RMSD with variables was determined using Chi-square test and multiple logistic

regression models for risk factors were created using SPSS 17.0 software. Results:  Prevalence of RMSD in 310 cases and controls was 42.58%; 95% CI: 37.08–48.08 and 31.61%; 95% CI: 26.43–36.79, respectively. RMS pain was marked by 194 individuals. Knee was the most common site of pain (33.4%). Prevalence of common RMSD was osteoarthritis knee (20.64%; 95% CI 16.14–25.16), frozen shoulder (16.45%; 95% CI: 12.32–20.58), diffuse idiopathic skeletal hyperostosis (14.52%; 95% CI: 10.6–18.44) and limited joint mobility (8.06%; 95% CI: 5.03–11.09). Age (P = 0.046), duration of T2DM (P < 0.001) and glycosylated

hemoglobin (P < 0.001) were found to have significant associations with RMSD. In logistic regression analysis, duration (OR: 1.467; 95% CI: 1.210–1.779) and severity (OR: 1.354; Selleckchem Fulvestrant 95% CI: 1.169–1.569) of T2DM were identified as the risk factors. Conclusion:  Thorough RMS examination should be included as an integral part of care Stem Cell Compound Library datasheet in T2DM patients. “
“Aims:  To determine what clinical factors relating to efficacy besides complications of orthopedic surgery for patients treated with anti-tumor necrosis factor (TNF)-α therapy (infliximab), we analyzed the clinical data of 52 cases of orthopedic surgery, such as total hip arthroplasy (THA), total knee arthroplasty (TKA), total shoulder arthroplasy (TSA), total elbow arthroplasty (TEA), arthroscopic synovectomy, foot arthroplasty, spine surgery, hand surgery and fracture. Methods:  We analyzed clinical

factors including age, disease duration, preoperative C-reactive protein (CRP), disease activity score (DAS)-28, matrix metalloproteinase (MMP)-3, and rheumatoid Carnitine palmitoyltransferase II arthritis particle-agglutination (RAPA) in 52 cases of rheumatoid arthritis (RA) undergoing orthopedic surgery. For complications of orthopedic surgery, signs of postoperative infection were recorded, including rubor, discharge, systemic infection and frequencies of wound dehiscence, as well as the incidence of any surgical complication requiring a secondary revision procedure were measured. Results:  Signs of infection or surgical complications occurred in two of 52 patients (3.8%). There is significant correlation between RAPA and improvement of CRP 3 months after surgery; however, there is no correlation between infection and clinical factors including age, disease duration, preoperative CRP, MMP-3, RAPA and the period until surgery after infliximab infusion. Conclusion:  Infliximab did not increase the risk of either infections or surgical complications occurring in patients with RA within 1 year of orthopedic surgery. Improvement of CRP after surgery is likely to be due to infliximab for high RAPA in RA patients.

Data regarding age, gender, country of exposure, the animal impli

Data regarding age, gender, country of exposure, the animal implicated in the exposure, prior preexposure vaccination, postexposure management with immunoglobulin and/or vaccine, site of injury, and time delay between date of exposure and treatment initiation were collected. Some travelers had started the treatment overseas and we considered human diploid cell vaccine (HDCV), purified chick embryo cell vaccine (PCECV), or purified vero cell rabies vaccine (PVRV) to be appropriate, as indicated in the HPA guidelines.

These vaccines can be Alpelisib safely interchanged.11 The management of the exposure was compared with HPA guidelines on the basis of the risk assessment (Table 2). Data analysis was performed using SPSS software (version 13 for Windows; SPSS Inc, New York, USA). A total of 142 patients attended PEP (Figure 1). Three of the medical records were not available and these were omitted from the analysis. Of the remaining 139 patients, 68 (48.9%) were female and 71 (51.1%) were male. The mean age of the cases was 35 (range: 2–84, SD: 16.8) with 8 missing data. Seven (5.3%) were younger than 10 years and 4 (2.9%) were older than 65 years (Figure 2). Exposures predominantly occurred in Thailand (31; 22.3%) and Turkey (31; 22.3%). Other countries involved were India (10; 7.2%) and Sri Lanka (5; 3.6%) (Figure 3). Most injuries involved the lower limb (67; 48.2%) followed by the Idelalisib hands

(26; 18.7%). Other sites of injuries include the trunk (25; 18%). Four patients (2.9%) had multiple sites of injuries. Dogs were implicated in the majority (69; 49.6%) of exposures, followed by cats (32; 23%) and monkeys (23; 16.5%). There were seven (5%) exposures to bats (Figure 4). Methisazone Two individuals did not have any animal exposure, but one had involved a contact with a positive rabies case abroad, with vomitus spilled on the body, and the other was a worried wife whose husband had been bitten by a confirmed rabid dog at multiple sites of the body. Most documented exposures were described as unprovoked (65; 46%). However, 27 (19%) individuals had no documentation of whether

exposures were provoked. PEP had been initiated overseas in 86 (61.9%) of the cases. Only 3 of the 78 (3.8%) cases meeting the UK criteria for administration of RIG received it while overseas. An additional 11 patients with initial treatment overseas received RIG on return to the UK; most patients were seen more than 7 days after the initiation of PEP. Because an antibody response to the active immunization is presumed to have occurred after 7 days, administration of RIG is unnecessary.12 Only 10.1% of the exposed travelers had received preexposure immunization. The median time from exposure to receiving rabies PEP was 1 day (range: 0–1,720 days; interquartile range: 0–7 days), regardless of whether it was initiated overseas or in the UK.

All comparisons were two tailed; P<005 was considered as signifi

All comparisons were two tailed; P<0.05 was considered as significant. Data were analyzed using spss 15. During the course of our experiments with SH-SY5Y neuroblastoma cells, we detected, using the EZ-PCR method, a mycoplasma contaminating our cell culture. The mycoplasma was identified as M. hyorhinis and designated as a neuroblastoma-derived M. hyorhinis (NDMH) strain. SH-SY5Y cells in the GM were infected with NDMH. NDMH-infected and noninfected (clean) cells were induced to differentiate, find more as described in Materials and methods. The morphology of the differentiated infected cells was similar to that of the clean cells,

with mycoplasma observed around the cells and in the medium of the infected cultures (Fig. 1a). PCR was carried out to determine the presence and absence of mycoplasmas in the cultured cells (Fig. 1b). Calpastatin in the control and in the NDMH-infected cells was analyzed by immunoblotting, as described in Materials and

methods. Calpastatin levels were significantly higher in the infected cells than in the clean cells, with levels of 208±20.3% (n=4), compared with the calpastatin levels in the clean cells (Fig. 2a and b). As can be seen in Fig. 2a, using a polyclonal anticalpastatin antibody, a major band of about 110 kDa was identified in both the clean and the infected cells. The NDMH did not exhibit the 110 kDa band, with a band of approximately 70 kDa observed (Fig. 2a). Using a monoclonal calpastatin antibody specific

for human calpastatin, the 110 kDa band was observed HIF activation in the clean and infected cells, whereas no bands were observed in the mycoplasma extracts, confirming that the mycoplasma did not have any human calpastatin (Fig. 2c and d). The results indicate that the high levels of calpastatin in the infected cells do not originate in the mycoplasma. Immunoblotting was also carried out for the identification of calpain. μ-Calpain was identified as a band of approximately 80 kDa, present in the clean and in the infected cells. It was not present in the NDMH (Fig. 3a). The μ-calpain levels in the infected cells were 139±9.7% (n=3), as compared with the levels in the clean cells (Fig. 3b). Calpain activation is generally considered to be associated with autolysis, with the 80 kDa subunit level indicating inactive calpain Sulfite dehydrogenase (Niapour et al., 2008), as is the case with inactive procaspases. The results thus suggested that calpain was less active in the infected cells than in the clean cells. In order to determine whether the higher calpastatin levels in the infected cells, observed by immunoblotting, interfere with calpain activity, casein zymography was carried out, as described in Materials and methods. Zymography allows the electrophoretic separation of calpastatin from calpain and estimation of calpain caseinolytic activity directly on the gel, without inhibition by the usual calpastatin content of the cell (Raser et al., 1995).

All results were subjected to statistical analysis with Student’s

All results were subjected to statistical analysis with Student’s t-test or one-way anova followed by the Newman–Keuls post hoc comparison test, with graphpad prism 4 software, in order to evaluate the significance of differences. The obtained significance levels are indicated in the text with the exact P-values up to 0.0001. Also, for post hoc tests, P-values are expressed by default as P < 0.05 or P < 0.001. We first investigated which C/EBP β isoforms were expressed by mature CGNs in culture, and whether they changed in survival/apoptotic conditions. To this aim,

primary cultures of rat CGNs were shifted from a medium with a high potassium concentration (25 mm KCl; K25), which is trophic for these neurons, to a medium with a low potassium APO866 concentration (5 mm KCl; K5), which is able to induce apoptosis, for study of the expression of the different C/EBP β isoforms in these conditions, which represent one of the most widely used models for studying neuronal survival/apoptosis (Contestabile, 2002). Immunocytochemistry of cultures shifted to a low-potassium medium demonstrated that immunoreactivity tended to decrease or disappear in apoptotic neurons as compared with neurons maintained selleck chemical in trophic conditions (Fig. 1A). Expression of C/EBP β isoforms was evaluated with western blot

analysis and the densitometry of total protein extracts at 8, 16 and 24 h after exposure to the apoptotic stimulus. This analysis showed that CGNs expressed three isoforms with the following molecular masses: 21 kDa, which matches the LIP isoform; 35 kDa, which matches the LAP2 isoform; and 50 kDa,

which matches the the LAP1 isoform post-translationally modified, probably sumoylated, as demonstrated below (Fig. 1B). Both the 50-kDa and 35-kDa bands decreased after 24 h in K5 medium, whereas the 21-kDa band increased under the same condition; the expression levels of both β-actin and GAP-43, used as controls, remained unaltered (Fig. 1B and C). In particular, comparison of the densitometric analysis data from at least three independent western blot experiments for each isoform/β-actin ratio at each time point was performed between the K25 and the K5 growth conditions by use of the two-tailed Student’s t-test; this revealed statistically significant changes at 24 h for the 35-kDa and 21-kDa isoforms (LAP2/β-actin, P = 0.023 and Z = 2.2734; LIP/β-actin, P = 0.036 and Z = 2.0969). In order to determine whether the LAP1 and LAP2 isoforms were transcriptionally activated in these conditions, phosphorylation of C/EBP β on Ser105, which is known to enhance C/EBP β transcriptional efficacy (Trautwein et al.,1993; Buck et al.,1999), was evaluated with western blot analysis in the same conditions, with a specific antibody. As shown in Fig. 1D, only the 50-kDa isoform was positive for this phosphorylation, which decreased with time in the K5 condition.

An alternative explanation is that these proteins are not Tat sub

An alternative explanation is that these proteins are not Tat substrates, but are translocated through another route, such as for example the Sec pathway. The next residue (Leu18 in AmyH) is also commonly a strongly hydrophobic residue, usually Leu, Ile, or Val, but changing this residue to Ala in SufI does not lead

to a block in its translocation buy Tanespimycin (Stanley et al., 2000). In contrast, it is critical in AmyH, as the L18A mutant is not translocated at all, shown both by the starch-plate assays and Western blotting (Fig. 3). This finding is corroborated by the observation that none of the haloarchaeal proteins in our datasets contained an Ala in that position. As outlined in the introduction, the haloarchaeal Tat system differs on several aspects from those of nonhalophilic Tat systems. Therefore, we could not exclude the possibility that, for instance, proteins with RK or KR motifs would also be Tat-dependent substrates. However, we found that residues that are critical to the translocation of an E. coli Tat substrate are also critical to the export of AmyH, including both arginine residues and the first of the pair of hydrophobic residues that follow the arginines. In addition, the second hydrophobic residue in the Tat motif is also essential for AmyH secretion, while

this residue seems to be of less importance in the E. coli Tat substrate SufI. The sequence logos indicate that this residue can also be another strongly hydrophobic amino acid such as Val or Ile, but further mutational

analysis has to be performed to confirm this. It is MG-132 ic50 interesting to note find more that the importance of this residue was already indicated by our bioinformatics analysis. The consensus motif for haloarchaeal Tat substrates can be denoted as (S/T)RRx(F/L)L, even though the first residue (Ser or Thr) does not appear to be essential for translocation. This information is useful in the prediction of Tat substrates encoded by genes found in haloarchaeal genomes. We do need to note, though, that our conclusions are based on the analysis of only one haloarchaeal Tat substrate, and it is clear that the characterization of other signal peptides is needed to understand the requirements for Tat-dependent export fully. D.K. was sponsored by a studentship from the Biotechnology and Biological Sciences Research Council, and A.B. was supported by a University Research Fellowship from the Royal Society. Table S1. Uniprot accession numbers and their Tat motifs. Please note: Wiley-Blackwell is not responsible for &!QJ;the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. “
“Salmonella enterica serovar Enteritidis is a major cause of human gastrointestinal tract disease, infection being due in large part to the consumption of contaminated eggs. Recent genome sequencing of S.

, 2008; McCamy et al, 2012) Saccades were identified with a mod

, 2008; McCamy et al., 2012). Saccades were identified with a modified version of the algorithm developed by Engbert and Kliegl (Engbert & Kliegl, 2003; Laubrock et al., 2005; Engbert, 2006; Engbert & Mergenthaler, 2006; Rolfs et al., 2006) with λ = 6 (used to obtain the velocity threshold) and

a minimum saccadic duration of 6 ms. To reduce selleck kinase inhibitor the amount of potential noise we considered only binocular saccades, that is, saccades with a minimum overlap of one data sample in both eyes (Engbert & Kliegl, 2004; Laubrock et al., 2005; Engbert, 2006; Engbert & Mergenthaler, 2006; Rolfs et al., 2006; McCamy et al., 2013a). Additionally, we imposed a minimum intersaccadic interval of 20 ms so that potential overshoot corrections might not be categorised as new saccades (Møller et al., 2002). Microsaccades were defined as saccades with magnitude < 1° in both eyes (Martinez-Conde et al., 2009, 2013). To calculate (micro)saccade properties such as magnitude and peak velocity we averaged the values for Selleck ALK inhibitor the right and left eyes. Supporting Information Table S3 includes

the descriptive statistics for microsaccades, saccades and drift. To avoid confounding factors and because (micro)saccades are sensitive to sudden visual and auditory stimuli (Rolfs, 2009), participants performed the experiment surrounded by a dark box while wearing noise-cancelling headphones. For the same reason, subjects received Sulfite dehydrogenase no

auditory or visual feedback when their gaze left the fixation dot (i.e. there was no fixation window around the central fixation target). Data from the first second of each 45-s trial were discarded to remove transient effects from the stimulus onset (Otero-Millan et al., 2012; McCamy et al., 2013c). Drift periods were defined as the eye-position epochs between (micro)saccades, overshoots and blinks. We removed 10 ms from the start and end of each drift period, because of imperfect detection of blinks and (micro)saccades, and we filtered the remaining eye-position data with a low-pass Butterworth filter of order 13 and a cut-off frequency of 30 Hz (Murakami et al., 2006; Cherici et al., 2012). To calculate drift properties (such as mean velocity and duration) we used the filtered data described above and removed an additional 10 ms from the beginning and end of each drift period to reduce edge effects due to the filter. Drifts < 200 ms were discarded. Finally, because drifts are not generally conjugate (Krauskopf et al., 1960; Yarbus, 1967; Martinez-Conde et al., 2004), we used data from both the left and right eyes. Thus, any given drift period had a duration, distance (length of the curve traced out by the drift), peak velocity and mean velocity for each eye. The cumulative distributions in Fig. 4 are the averages across subjects; each subject’s distribution is that of the drift mean velocities from both eyes.

The three most well-studied components of the nitrogen regulatory

The three most well-studied components of the nitrogen regulatory circuit that commonly impact fungal pathogenesis are the ammonium permeases (the nitrogen availability sensor candidate), ureases (a nitrogen-scavenging enzyme) and GATA transcription factors (global regulators of nitrogen catabolism). In certain species, the ammonium permease induces a morphological switch from yeast to invasive filamentous growth forms or infectious spores, while in others, urease is a bona fide virulence factor. In all species studied thus far, transcription of the ammonium permease and urease-encoding genes is modulated by GATA factors. Fungal pathogens

therefore integrate the expression of different virulence-associated OSI-744 price phenotypes into the regulatory network controlling nitrogen catabolism. “
“Bacteria have the exquisite ability to maintain a precise diameter, cell length, and shape. The dimensions of bacteria size and shape are a classical metric in the distinction of bacterial species. Much of what we know about

the particular morphology of any given species is the result of investigations of planktonic cultures. As we explore http://www.selleckchem.com/products/ldk378.html deeper into the natural habitats of bacteria, it is increasingly clear that bacteria can alter their morphology in response to the environment in which they reside. Specific morphologies are also becoming recognized as advantageous for survival in hostile environments. This is of particular importance in the context of both colonization and infection in the host. There are multiple examples of bacterial pathogens that use morphological changes as a mechanism for evasion of host immune responses and continued persistence. This review will focus on two systems where specific morphological changes are essential for persistence in animal models of human disease. We will also offer insight into the mechanism underlying the morphological changes and how these morphotypes aid in persistence. Additional examples of morphological changes associated with survival will be presented. “
“The Tat pathway is

a common protein translocation system that is found in the bacterial cytoplasmic membrane, as well as in the cyanobacterial and plant thylakoid membranes. It is unusual in that the Tat pathway transports mafosfamide fully folded, often metal cofactor-containing proteins across these membranes. In bacteria, the Tat pathway plays an important role in the biosynthesis of noncytoplasmic metalloproteins. By compartmentalizing protein folding to the cytoplasm, the potentially aberrant binding of non-native metal ions to periplasmic proteins is avoided. To date, most of our understanding of Tat function has been obtained from studies using Escherichia coli as a model organism but cyanobacteria have an extra layer of complexity with proteins targeted to both the cytoplasmic and thylakoid membranes. We examine our current understanding of the Tat pathway in cyanobacteria and its role in metalloprotein biosynthesis.

26; 95% CI 007–101) There was also a trend to lower HCV viral

26; 95% CI 0.07–1.01). There was also a trend to lower HCV viral load in this group, which may go some way to explaining this. Also, in a small French cohort of co-infected women (29% on cART), rate of transmission see more did not differ significantly between children

born by vaginal delivery or CS [227]. cART should be given to all HCV/HIV co-infected pregnant women, regardless of CD4 cell count or HIV viral load because of the evidence of increased HIV transmission in co-infected mothers. 6.2.7 Where the CD4 cell count is < 500 cells/μL, cART should be continued if HCV viraemia exists because of the increased risk of progressive HCV-related liver disease. Grading: 1B 6.2.8 Where the pre-cART CD4 cell count was > 500 cells/μL and there is no HCV viraemia or fibrosis, cART should be discontinued. Grading: 2C 6.2.9 Where the CD4 cell count is > 500 cells/μL and there is HCV viraemia and evidence of liver inflammation or fibrosis, continuing cART is preferable because of a benefit on fibrosis progression.

Grading: 2B 6.2.10 Where the CD4 cell count is between 350 and 500 cells/μL and there is no evidence of viraemia, inflammation or fibrosis, continuing cART is recommended. Grading: 1C The decision to continue ARV or not postpartum depends on both HIV and HCV factors. There is consensus amongst guidelines that all persons with active (HCV-viraemic) co-infection should receive cART if their CD4 cell count is < 500 cells/μL [175, 176, 228]. In those women with CD4 cell counts of 350–500 cells/μL

Veliparib concentration who have cleared infection either spontaneously (around 25%) or after treatment and with a sustained virological response (SVR) and who have normal liver histology as judged by biopsy or hepatic elastometry, consideration should be given to continuing cART where the patient expresses a preference to do so. This is because until the completion of the randomized PROMISE trial, which addresses the question of whether to continue cART postnatally in mothers with CD4 cell counts > 400 cells/μL, there is equipoise as to correct management. In those with CD4 cell counts over 500 cells/μL, who received Lck cART to prevent MTCT, and who are not HCV-viraemic and have no evidence of established liver disease, ARVs can be discontinued. Without additional risk factors (such as alcohol, steatosis) and assuming they do not get re-infected, these women should have no further histological progression of their liver. In women with CD4 cell counts over 500 cells/μL who have established liver disease (inflammation or fibrosis), therapy should be continued. Interruption of ART in the SMART study was shown to lead to a greater risk of non-opportunistic disease-related death, particularly among those with HIV/HCV co-infection.