, 2001), gingival fibroblasts and T cells (Belibasakis et al., 2010), which are crucial for the induction of cytokine responses and the establishment of chronic inflammation in periodontitis (Holzhausen et al., 2010; Fagundes et al., 2011). Gingipains can also stimulate IL-6 production by oral

epithelial cells Selleck BGB324 (Lourbakos et al., 2001) and IL-8 production by gingival fibroblasts (Oido-Mori et al., 2001), enhancing the inflammatory responses. However, they can also proteolytically inactivate both anti-inflammatory (IL-4, IL-5) and pro-inflammatory (IL-12, IFN-γ) cytokines (Yun et al., 1999, 2001, 2002; Tam et al., 2009). A number of particularly interesting effects are exerted by the gingipains on components of the complement system. Arg-X gingipains can cleave the C5 molecule, resulting in release of its C5a component, which is crucial for enhancing learn more the recruitment of PMNs (Wingrove et al., 1992; Imamura et al., 2001). On the other hand, Lys-X can inactivate the C5a receptor on PMNs, an action that may actually impair their recruitment (Jagels et al., 1996a, b). Along this line, the Arg-X gingipains can degrade the C3 molecule, potentially contributing to decreased bacterial opsonization (Schenkein et al., 1995). This property could confer increased resistance of P. gingivalis to bactericidal activity. Apart from their effect on immune responses, gingipains may

also be involved in the binding of P. gingivalis to host cells, as Rgp–Kgp complexes have been shown to mediate adherence on gingival epithelial cells and gingival fibroblasts (Chen et al., 2001; Grenier et al., 2003; Andrian et al., 2004). Interestingly, when P. gingivalis intracellularly invades Glutathione peroxidase gingival epithelial cells, expression of gingipain is downregulated (Xia et al., 2007). Gingipains may also affect vascular permeability and bleeding at the periodontal site. They can proteolytically activate plasma kallikrein and bradykinin, or alternatively increase the release of thrombin and prothrombin,

which can result in increased vascular permeability and PMN influx (Imamura et al., 1994, 1995a). Moreover, by degrading fibrinogen (Scott et al., 1993), they may contribute to inhibition of blood coagulation and increase bleeding at the site (Imamura et al., 1995a) , thus enhancing the availability of hemin required for P. gingivalis growth. Collectively, studies in various experimental systems indicate that gingipains have seemingly contradicting actions on the innate immune responses, hampering interpretation of their role in the pathogenesis of periodontitis. Nevertheless, such differences may be reconciled by the existence of a concentration gradient of gingipains in the tissue (Pathirana et al., 2010). Closer to the gingival epithelial barrier where the biofilm resides, gingipain concentrations are high, causing degradation or deregulation of various components of the immune response.

“
“In the case of coinfection with HIV and hepatitis B virus (HBV) and/or hepatitis C virus (HCV), hepatic disease progression is often accelerated, with higher rates of liver cirrhosis and liver-related mortality. We aimed to evaluate the performance of the rapid

tests used routinely to detect HBV surface antigen (HBsAg) and anti-HCV among HIV-infected patients in Guinea-Bissau. Blood samples from HIV-infected patients in Guinea-Bissau were stored after testing for HBsAg and anti-HCV with rapid tests. Samples were subsequently re-tested for HBsAg and anti-HCV in Denmark. Two rapid tests were used in Guinea-Bissau: HBsAg Strip Ref 2034 (VEDA.LAB, Alençon, France; sensitivity 62.3%; specificity 99.2%) and HEPA-SCAN (Bhat Bio-Tech, Bangalore, India; sensitivity 57.1%; specificity 99.7%). In the two tests the ability to obtain the correct outcome depended on

the antigen and antibody MS-275 price concentrations, respectively. Sex, age, CD4 cell count and antiretroviral therapy status did not differ between false negative and true positive samples SB203580 clinical trial in either of the tests. The study is limited by a low number of anti-HCV positive samples. New diagnostic rapid tests should always be evaluated in the setting in which they will be used before implementation. “
“To study determinants of late HIV diagnosis in a low-HIV-prevalence (<0.1%) country where HIV spread among men who have sex with men (MSM) and heterosexuals in the 1980s, and among injecting drug users (IDUs) in the late 1990s. Newly diagnosed HIV cases referred to the Helsinki University Central Hospital between 1985 and 2005 were reviewed to identify determinants of late HIV diagnosis, defined as diagnosis when the first CD4 count was <200 cells/μL, or when AIDS occurred within 3 months of HIV diagnosis. Determinants of late diagnosis were analysed using multivariate logistic regression. Among 934 HIV cases, 211 (23%) were diagnosed late. In the first 4-year interval of each sub-epidemic

(1985–1989 for MSM and heterosexuals, 1998–2001 for IDUs), rates of late HIV diagnosis much were 13%, 18% and 6%, respectively, but increased thereafter to 29%, 27% and 37%. Late diagnosis was associated with non-Finnish ethnicity, older age, male gender, lack of earlier HIV testing, diagnosis at health care settings and later stage of the sub-epidemic. The lower rate of late diagnosis in the first 4-year interval of each HIV sub-epidemic suggests that the early stages of the HIV epidemic in Finland were detected early. This factor may have contributed to the low prevalence of HIV infection in Finland. The stage and age of the epidemic should be taken into account when interpreting the data on late HIV diagnosis, especially in cross-country comparisons. Early diagnosis of HIV has become a crucial issue today.

, 1998; Takahashi et al., 2000; Sanyal & Carbon, 2002). Inner KT assembly is considered to be initiated by CENP-A deposition. CENP-A recruitment can occur through multiple pathways, which involve several genetic and epigenetic factors. Recruitment of CENP-A takes place at different stages of the cell cycle. It occurs during 17-AAG S phase and anaphase in S. cerevisiae (Pearson et al., 2004; Shivaraju et al., 2012),

at S and G2 phases in S. pombe (Chen et al., 2003; Takayama et al., 2008) and at least in anaphase in C. albicans (Shivaraju et al., 2012). Further experimentation is required to investigate whether CENP-A deposits at early S phase when the CEN DNA is replicated in C. albicans (Koren et al., 2010). An evolutionarily conserved nonhistone DNA-binding chaperone Scm3/HJURP is an essential component for KT assembly. This family of proteins has the propensity to bind to the A-T rich CEN DNA and contains a histone chaperone domain, which is required for Cse4/H4 deposition in vivo (Xiao et al., 2011). Scm3 is required for CENP-A deposition at the CEN both in S. cerevisiae and S. pombe (Camahort et al., Selleck Trametinib 2007; Mizuguchi et al., 2007; Stoler et al.,

2007; Pidoux et al., 2009; Williams et al., 2009). Moreover, over-expression of Scm3 results in a reduction in Cse4 at the CEN in S. cerevisiae (Mishra et al., 2011). Although Scm3 is required for Cse4 localization at the CEN, but its own localization at the CEN is independent of Cse4 in both S. cerevisiae and S. pombe (Williams et al., 2009; Luconi et al., 2011). Similarly, another KT protein essential for CENP-A localization is CENP-C. The localization of CENP-A is dependent on CENP-C in both S. pombe (Tanaka et al., 2009) and C. albicans (Thakur & Sanyal, 2012). In addition to these proteins, epigenetic regulation of CENP-A deposition (reviewed in Roy & Sanyal, 2011) has been demonstrated in S. pombe (Steiner & Clarke, 1994)

and C. albicans (Baum et al., 2006). Ndc10, a part of the point CEN-specific CBF3 complex, has been shown to influence the recruitment of most of the KT proteins including CENP-A in S. cerevisiae (Ortiz et al., 1999; Russell et al., 1999; Goshima Methocarbamol & Yanagida, 2000; He et al., 2001; Janke et al., 2001, 2002). It is not clear that Ndc10 is required only in S. cerevisiae because an obvious homolog is not identified in S. pombe or C. albicans. On the other hand, Ams2 at S phase (Chen et al., 2003) and Hip1 at G2 phase (Takayama et al., 2008) influence CENP-A loading in S. pombe. The cell cycle phase–specific loading of CENP-A has also been shown to be affected by Mis6 through Sim3 in S. pombe (Takahashi et al., 2000; Dunleavy et al., 2007). Interestingly, proteins from the middle and outer KT affect the localization of CENP-A in C. albicans (Roy et al., 2011; Thakur & Sanyal, 2012). The Dam1 complex, a fungal-specific outer KT protein complex, which has no known role in CENP-A recruitment in S.

There are approximately 350 million hepatitis B carriers and about 33 million Venetoclax HIV-infected people world-wide [69,70]. As the routes of transmission for these infections are similar, there is a significant rate of coinfection in patients. Underlying HIV infection increases the chance of HBV chronicity [71]. There are no comprehensive data from the UK defining HIV/HBV coinfection rates. However, data from the EuroSIDA study [72] showed a 9.1% prevalence of HBsAg coinfection in participating northern European centres. In a survey of 100 UK clinics in 2004, the

dual HIV/HBV infection rate was estimated to be 3–10% of patients in 93% of clinics [73]. In many parts of Africa, HIV/HBV coinfection is common, as seen in South Africa (5%) or Malawi (20%) Akt inhibitor [74,75]. Recent

immigrants from Africa represent the largest group of newly diagnosed HIV-positive people in the UK [76] and therefore high coinfection rates are to be expected. High rates of HBV infection are also seen in IDUs and therefore HIV/HBV is relatively common in this group of patients [77] 4.1.2.1 The influence of HBV on HIV infection. The natural history of HIV infection does not seem to be influenced by hepatitis B [71,72,78] although there is an increased rate of antiretroviral-related hepatotoxicity, and immune-reconstitution hepatitis [79–81]. 4.1.2.2 The influence of HIV on HBV infection. Although the evidence remains conflicting, acute infection with HBV is more likely to be mild or asymptomatic in HIV-positive patients compared with those who are HIV-negative [82,83]. The rate of hepatitis B clearance is

also lower, with up to 20–40% of infected patients progressing to chronic (>6 ADP ribosylation factor months) infection [82,83]. Progression to liver cancer is more rapid, with HIV-positive patients with HBV infection developing liver cancer younger than patients with HBV infection alone [52, 82–84]. Once HBV infection is established, liver damage is immunopathic (the immune response to the virus causes most of the liver damage) so liver disease would be expected to be less severe in HIV-related immunosuppression. However, recent evidence suggests that alanine aminotransferase (ALT) and liver inflammatory scores in HIV coinfected patients are no different to those in HBV monoinfected patients [78]. At very high levels of viral replication, HBV may have a direct cytopathic effect. Coinfection with HIV is generally accompanied by an increase in HBV replication [78], which might explain the evidence for an increased rate of progression to cirrhosis and death [72,78,85,86] when compared with HBV monoinfected patients. There is also a reduction in the rate of natural clearance of HBeAg by about 60% in coinfected patients compared with HIV-negative patients [87]. However, there are reports of patients clearing chronic HBV infection with the recovery of CD4 cell count responses following ART [88,89].

By parametrically varying SNRs, we found that children benefited significantly less from observing visual articulations, displaying considerably less audiovisual enhancement. The findings suggest that improvement in the ability to recognize speech-in-noise and in audiovisual integration during speech perception

continues quite late into the childhood years. The implication is that a considerable amount of multisensory learning remains to be achieved during the later schooling years, and that explicit efforts to accommodate this learning may well be warranted. “
“Mechanisms of place cell replay occurring during sharp-wave ripples (SPW-Rs) remain obscure due to the fact that ripples in vitro depend on non-synaptic mechanisms, presumably via axo-axonal gap junctions check details between pyramidal cells. We suggest a model of in vivo SPW-Rs in which synaptic excitatory post-synaptic

potentials (EPSPs) control the axonal spiking of cells in SPW-Rs: ripple activity remains hidden in the network of axonal collaterals (connected by gap junctions) due to conduction Selleckchem PD0325901 failures, unless there is a sufficient dendritic EPSP. The EPSP brings the axonal branching point to threshold, and action potentials from the collateral start to propagate to the soma and to the distal axon. The model coherently explains multiple experimental data on SPW-Rs, both in vitro and in vivo. The mechanism of synaptic gating leads to the following implication: a sequence of pyramidal cells can be replayed at ripple frequency by the superposition of subthreshold dendritic EPSPs and ripple activity in the axonal plexus. Replay is demonstrated in both forward and reverse directions. We discuss Methane monooxygenase several testable predictions. In general, the mechanism of synaptic gating suggests that pyramidal cells under certain conditions can act like a transistor. “
“The perirhinal

cortex, which is critical for long-term stimulus–stimulus associative memory, consists of two cytoarchitectonically distinct subdivisions: area 35 (A35) and area 36 (A36). Previous electrophysiological studies suggested that macaque A36 is involved in both association and retrieval processes during a visual pair-association task. However, the neuronal properties of macaque A35 have never been examined because A35 is located in a very narrow region, which makes it difficult to systematically record single-unit activity from there. In the present study, we overcame this technical difficulty for targeting A35 by combining magnetic resonance imaging-guided in-vivo localization with postmortem histological localization. This two-track approach enabled us to record from 181 A35 neurons in two macaque monkeys while they performed a pair-association task. Among these neurons, 64 showed stimulus-selective responses during the cue period (cue-selective neurons), whereas 18 did during the delay period (delay-selective neurons).

The initial list of questions was intentionally over-inclusive to allow for expert opinion to evaluate a wide range of potential research topics. At the June 2006 Northern

European Conference on Travel Medicine (Edinburgh, Scotland), the research questions were presented, discussed, and revised by the attending members of the Research Committee. The questions were then offered for comment to the other committees of the ISTM. The research priorities were compared for consistency to the Travel Medicine Practice Guidelines20 and then transformed into a priority list which was presented at a poster session at the 10th Conference of the ISTM.21 A survey for modifications was administered Selleckchem Metabolism inhibitor to the convenience sample of those attending the poster session. The Writing Group made modifications then further reviewed to choose areas with: (1) the most commonly arising questions; (2) the highest impact on health (severe OSI-744 cost disease with lack of therapy); and (3) the most likely to effect on cost savings. A literature search was then done to ensure

that adequate data answering these questions did not already exist. The research questions listed below (and in Table 2) are not an exhaustive list of all possible study areas, particularly because new issues are continuously emerging, and research priorities inevitably change Chorioepithelioma over time. Nevertheless, this provides a starting point by listing some of the data gaps that have been identified as priority areas and which could feasibly be addressed with further research. Some research questions that were raised early in the course of this initiative have been adequately answered by recent studies and have been removed from the current list. Table 2 shows research questions for which data are currently lacking and for which an improved evidence base for pre-travel interventions is required. Of particular concern is that 60% to 80% of travelers from North America,22,23 68% from Australasia,24 and 48% from

Europe17 do not access pre-travel services. There are guidelines based largely on expert opinion providing travel medicine recommendations for different types of travelers on different itineraries (Infectious Disease Society of America Guidelines20), but strategies to access these patients are lacking. The lack of pre-travel preparation has been shown to result in a low overall level of knowledge of risk and preventive practices. There is an association between failing to seek travel medicine services and acquisition of malaria.25 Although difficult to prove and fraught with potential biases, this association may hold for other adverse health impacts associated with travel.

Since the first report of ESBLs in 2002 (Chanawong

et al., 2002), blaCTX-M has been predominant in mainland (Yu et al., 2007; Liu et al., 2009). In this multicentre study, the prevalence of ESBL production in K. pneumoniae has been demonstrated to be about 40%. Of 158 ESBL-producers, the isolates harboring ESBL genes and blaCTX-M-14 were 94.3% and 49.4%, respectively, and were shown to increase 10% and 9% to those in another large-scale study (Yu et al., 2007), respectively. The proportion of blaCTX-M increased 12% compared to the percentage (72.3%) described in a report of southern China three years ago (Liu et al., 2009) and doubled the percentage reported nine years ago (Li et al., 2003). Because the usage of plasmid-based amplification method in this study and the potential selleck false-negative products

owing to the unbinding on some novel bla, the detection of β-lactamase genes AG-14699 may have been underestimated. Although there are some differences in the source of the isolates in our study as compared to the studies mentioned above, our results clearly suggest the increasing prevalence of blaCTX-M in K. pneumoniae in China. CTX-M-type ESBLs exhibit powerful activity against cefotaxime and ceftriaxone but generally not against ceftazidime, and several variants with enhanced ceftazidimase activity have been reported (Poirel et al., 2002; Bonnet et al., 2003; Branched chain aminotransferase Rossolini et al., 2008). In this study, it was observed that the isolates harboring CTX-M-15 or CTX-M-27 alone exhibited higher resistance rates to ceftazidime and aztreonam than that in subgroup CTX-M-14 without other ESBLs

(Table 2). Further, a high percentage of isolates harboring blaCTX-M-27 demonstrated the MDR phenotype. To our knowledge, this is the first study about the high prevalence of CTX-M-27 in Enterobacteriaceae in China. This warrants for an active surveillance to monitor these resistant bacteria. The overall resistance rates to the tested β-lactam antimicrobial agents were over 30% except for cefepime, piperacillin/tazobactam, and cefotetan in this study. As shown in Table 2, only 9.3% isolates harboring CTX-M-14 alone showed resistance to cefepime, but 50% isolates harboring CTX-M-15 exhibited resistance (P < 0.01), and a 100% resistance rate when CTX-M-15 coexisted with other ESBLs. Nevertheless, piperacillin/tazobactam show only 10.1% resistance rate in vitro, although the proportion increased to 26.7% when the isolates contained two types of ESBLs(blaCTX-M + blaSHV)(Table 1). Several clinical intervention studies also supported that piperacillin/tazobactam may contribute to preventing the ESBL-producing K. pneumoniae outbreaks (Lee et al., 2007; Tangden et al., 2011). These properties highlight the value of piperacillin/tazobactam as empirical therapy for infections by suspected organisms possessing a single ESBL (especially the blaCTX-M).

Since their discovery in 2003, they have been shown to play varying roles in the bacterial cell architecture such as crescentin (CreS) in Caulobacter crescentus, which establishes and maintains its vibroid/coiled-cell shape; FilP in Streptomyces LBH589 cost coelicolor plays a role in cell rigidity; and finally, in Helicobacter pylori, two IF-like proteins (Ccrp59 and Ccrp1143) play roles in maintaining cell morphology (Ausmees et al., 2003; Bagchi, 2008; Waidner et al., 2009). Here, we show that the B. bacteriovorus genome contains one predicted IF-like protein (CCRP) and

we investigate its role in prey cell entry and in B. bacteriovorus cell morphology. A full list of the strains used in this study can be found in Table 1. Genome-sequenced strain B. bacteriovorus HD100 (Stolp Everolimus mw & Starr, 1963; Rendulic, 2004) was used throughout this study,

and was grown by predation on Escherichia coli S17-1 (Simon et al., 1983) in Ca/HEPES buffer using standard culturing methods described in Lambert et al. (2003). Ca/HEPES buffer supplemented with 50 μg mL−1 kanamycin (Kn) and kanamycin-resistant E. coli S17-1:pZMR100 prey were used to maintain B. bacteriovorus strains with genome-integrated kanamycin resistance cartridges (Rogers, 1986). Gene interruptions by kanamycin cassette insertion into B. bacteriovorus HD100 were carried out as described previously (Lambert et al., 2003; Evans et al., 2007). Briefly, constructs were prepared by the amplification of a region of the HD100 genome containing either ccrp (Bd2697) or Bd2345 and 1 kb flanking genomic DNA, and were inserted into the pGEM7 vector (Promega); subsequent gene inactivation was achieved using kanamycin cassette insertion into the unique NruI site of the ccrp ORF and the EcoRV Osimertinib site of the Bd2345 ORF, and transferred into the mobilizable pSET151 plasmid (Bierman, 1992), forming the pAKF22 and pLH008 deletion constructs, respectively. These were then introduced into B. bacteriovorus cells by conjugation using the S17-1 donor strain described fully in Evans et al. (2007); candidate mutants were screened and gene knockout candidates were confirmed by Southern

blot. We were able to isolate the ccrp mutant directly from a predatory host-dependent culture, without the need to go through host–prey-independent growth for selection. Sample preparations were carried out using the methods described in Borgnia et al. (2008). Images were taken on a Tecnai T12 transmission electron microscope (TEM). Five microlitre droplets of bacterial cells were applied to holey carbon grids (Quantifoil MultiA; Micro Tools GmbH, Germany), previously glow discharged for about 30 s and coated, for scale, with 15 nm protein A–gold conjugates (BB International, Cardiff, UK). The grids were manually blotted and quenched in liquid ethane using a manual gravity plunger. Vitrified specimens were then transferred into an FEI Tecnai 12 TEM or a Tecnai Polara TEM (FEI Company, Hillsboro, OR).

In the NNRTI group, eight events of hepatotoxicity in 122 PYT were observed in the first year of therapy (6.6%), while for the whole period beyond 1 year 16 episodes in 569 PYT were found (2.8%; P = 0.04). Thus, the risk of developing hepatotoxicity was significantly higher in the first year after NNRTI treatment initiation. All hepatotoxic events in our DNA Synthesis inhibitor population occurred in 18 patients; four of them (22.2%) accounted for multiple LEEs over the years. All of these patients continued their NNRTI use

despite these multiple events. Five patients (4.1%) accounted for the five events of severe hepatotoxicity; none of them discontinued therapy because of this severe event, as the LEE had either resolved spontaneously or was attributed to other medication which was adjusted or stopped. One hundred and four patients (85.2%) did not show any clinically relevant hepatotoxicity. This retrospective cohort analysis shows that prolonged use of NNRTIs (≥ 3 years) is not accompanied by an increasing incidence of hepatotoxicity compared with the first year of NNRTI use. We did not find a difference in the risk for developing hepatotoxicity between patients using either EFV or NVP for ≥ 3 years. HCV coinfection was independently associated with the development of LEEs during NNRTI treatment. The incidence of hepatotoxicity did not differ significantly between

the NNRTI and PI groups. To date, a few studies have reported on the liver safety of long-term PFT�� order use of NVP and EFV [6, 9-11]. Most of these studies gave rates of discontinuation because of hepatotoxicity, but did not give the exact number of hepatotoxic events or describe HSP90 the time course. The significantly higher risk of liver toxicity in patients with an HCV/HIV coinfection using NNRTI has been reported before [1, 12]. The intriguing question is whether the occurrence of LEEs in these patients is indeed a marker of drug toxicity or the result of liver enzyme fluctuations in the context of chronic viral hepatitis infection [13]. It is remarkable that, although a higher proportion of patients in the PI group were HIV/HCV-coinfected,

there was no difference with the NNRTI group in terms of the number of hepatotoxic events. We observed a distinct pattern in the incidence of hepatotoxic events over the years of therapy. The number of hepatotoxic events in the first year of NNRTI therapy was significantly higher than in the period that followed. It seems that the number of events declined over the years, even in patients who had already experienced moderate to severe hepatotoxicity in the first year. This observation suggests that it is safe to continue NNRTI-based HAART, even in case of (asymptomatic) hepatotoxicity in the first year of therapy. The debate regarding the pathogenesis of NNRTI-induced hepatotoxicity is ongoing.

Vincent’s Hospital, Sydney, Australia, were invited to participate in a prospective study of the neurological/neuropsychological (NP) complications of HIV disease. The see more inclusion criteria were advanced HIV disease (Centers for Disease Control and Prevention stage C3; see Cysique et al. [22] for details), being on CART (at least three antiretroviral drugs) and being clinically stable. Therefore, this cohort was composed of individuals who had been historically immunosuppressed. Detailed information on this cohort has been published elsewhere [22]. Briefly, for advanced HIV-infected individuals, mode of infection was homosexual

contact in 93% of cases (94 of 101), injecting drug use (IDU) in two cases, transfusion in one case, unknown in two cases and heterosexual contact in two cases. The injecting drug users denied current drug use and this was confirmed by their clinician. Nineteen patients with a previous HIV-related brain disease included 16 patients with AIDS Dementia Complex (ADC)

stage 0.5 or 1, of whom two had toxoplasmosis in addition to ADC, one had progressive multifocal leukoencephalopathy in addition to ADC and one had cryptococcal meningitis in addition to ADC; and three had cryptococcal meningitis. These 19 patients did not differ from the other patients KU57788 in their neuropsychological performance. Thirty seronegative controls were also enrolled in this study to develop a standard NP reference (Table 1). The group of HIV-negative controls was recruited in the same Sydney Cediranib (AZD2171) metropolitan area as the HIV-positive sample. On average, they did not differ from the HIV-positive sample for age [mean ± standard deviation (SD): HIV-positive, 48.51 ± 9.32 years; HIV-negative, 47.40 ± 9.39 years; P=0.54], education (HIV-positive, 14.05 ± 2.85 years; HIV-negative, 15.00 ± 3.08 years; P=0.15), gender (all male) or premorbid intelligence quotient (HIV-positive, 115.71 ± 8.64; HIV-negative, 117.40 ± 6.61; P=0.32). Their overall NP performance was well within the normal range

(mean ± SD: 0.001 ± 0.20), providing a valid reference for definition of NP impairment in the HIV-positive group. The HIV-negative individuals were seronegative, on a screening test (enzyme-linked immunosorbent assay) for HIV-1-specific antibody, at least 3 months prior to the examination and screened for significant neurological or psychiatric diseases. An interview on medical history was conducted in order to exclude participants with neurological or psychiatric disease (epileptic disorder, traumatic brain injury with loss of consciousness >30 min, or current major depressive episodes) or any significant medical history (cardiovascular diseases). All denied a history of IDU. CNS penetration effectiveness (CPE) was computed using Letendre et al. [16] criteria. Depression Anxiety Stress Scale (DASS) scores are reported as standard scores derived from published normative data [23].