Compared with survivors, the deceased patients were older, had a higher BMI and greater menopausal status at diagnosis, were more likely to have reported tubal ligation prior to diagnosis, and had higher parity and ever breastfeeding. A higher proportion of deceased patients was diagnosed at an advanced stage, with ascites and poorly differentiated histopathological grade, and chemotherapy after surgery. There were no significant differences in age at menarche, hysterectomy, hormone replacement therapy, oral contraceptive use, and family history of ovarian cancer between the living and deceased patients. The survival curves in the ovarian

cancer patients according to tubal ligation status were distinctly different visually (see Fig. 1) and, based on the log-rank test for equality of survival distributions, the difference was not a chance occurrence PD-1 antibody (P < 0.001). Only 21 (38.9%) of 54 patients who had tubal ligation survived to the time of interview, in contrast to 95 women (67.4%) still alive among the 141 women without tubal ligation. Table 3 shows the crude and AZD1152-HQPA adjusted mortality hazard ratios and 95% CI for epithelial ovarian cancer according to selected factors. Compared with patients in FIGO stage I, the adjusted HR were 12.25 (95% CI 2.47–60.78; P < 0.001) and 24.54 (4.50–133.8; P < 0.001) for those who were diagnosed at FIGO stage III and IV. An insignificant

increased HR was observed for ascites 1.27 (95% CI 1.00–1.60; P = 0.05). There was no significant association between cancer survival and age, BMI, World Health Organization (WHO) grade of differentiation, and chemotherapy status. Adjusted HR and 95% CI for reproductive, gynecological and hormone factors are shown in Table 4. HR significantly increased with tubal ligation prior to diagnosis. Compared to patients without tubal ligation, the adjusted HR was 1.62 (95% CI 1.01–2.59; P = 0.04) for patients who had tubal ligation. There was no significant association found with age at menarche, menopausal status, parity, breastfeeding, hormone replacement therapy, oral contraceptive use, and

hysterectomy. The study found that tubal ligation prior to diagnosis had an independently adverse influence on epithelial ovarian cancer survival in Chinese women. The study had a relatively small sample Phosphoglycerate kinase size and exposures to some factors were uncommon (e.g. only four cases were exposed to estrogens). There was no relationship found between other reproductive, gynecological, and hormone factors and survival of ovarian cancer, in contrast to substantial effects of these factors on the incidence of the disease reported elsewhere.2–9 In addition to the evidence presented here, previous tubal ligation or hysterectomy, multiparity, oral contraceptive use and breastfeeding have been reported as protective factors against ovarian cancer incidence in several others studies.

More than 50% of the faint type colocalized with NG2 and 91% with oligodendrocyte transcription factor-2, whereas 94% of NG2-immunoreactive and 45% of oligodendrocyte transcription factor-2-immunoreactive cells were faintly CNPase-enhanced green fluorescent protein positive. Based on the complexity of the overall structure, the three types probably represent stages of a maturation process such that one subtype can morph into another. Thus, the least complex ‘smooth’ cell

would represent the youngest oligodendrocyte that matures into the stellar type and eventually progresses to become the most complex ramified oligodendrocyte. Investigation of the distribution pattern revealed that the highest density of oligodendrocytes was Silmitasertib purchase found in the stratum lacunosum-moleculare and the hilar region. PLX4032 chemical structure The distribution analysis of oligodendrocyte subclasses revealed a tendency for different cell types to segregate in large non-overlapping areas. This observation suggests that morphologically, and possible functionally, different oligodendrocytes are topographically segregated. “
“The addictive

properties of morphine limit its clinical use. Learned associations that develop between the abused opiate and the environment in which it is consumed are engendered through Pavlovian conditioning processes. Disruption of the learned associations between the opiate and environmental cues may else be a therapeutic approach to prevent morphine dependence. Although a role for the δ-opioid receptor in the regulation of the rewarding properties of morphine has already been shown, in this study we further characterized the role of the δ-opioid receptor in morphine-induced conditioned responses by examining the effect of a selective δ2-opioid receptor antagonist (naltriben), using a conditioned place preference paradigm in rats. Additionally, we used a subcellular fractionation technique to analyze the synaptic localization of μ-opioid and δ-opioid receptors

in the hippocampus, in order to examine the molecular mechanisms that may underlie this morphine-induced conditioned behavior. Our data show that the administration of 1 mg/kg naltriben (but not 0.1 mg/kg) prior to morphine was able to block morphine-induced conditioned place preference. Interestingly, this naltriben-induced disruption of morphine conditioned place preference was associated with a significant increase in the expression of the δ-opioid receptor dimer at the postsynaptic density. In addition, we also observed that morphine conditioned place preference was associated with an increase in the expression of the μ-opoid receptor in the total homogenate. Overall, these results suggest that modulation of the δ-opioid receptor expression and its synaptic localization may constitute a viable therapeutic approach to disrupt morphine-induced conditioned responses.

An in vitro study showed that an acute physiological dose of E2 administered to OVX rat striatal tissue produces a rapid conversion of DA D2Rs from their high to low affinity state (Levesque & Dipaolo, 1988). Similarly, the affinity state of DA D2Rs fluctuates across the estrous cycle with the most DA D2Rs in the high affinity state during diestrus when estrogen is low and most in the low affinity state during behavioural estrus and proestrus (Dipaolo et al., 1988).

In addition, chronic replacement of E2 in OVX rats results in an increase in striatal DA D1 receptor (D1R) binding, suggesting that E2 affects both the affinity state of D2Rs and the binding of D1Rs (Levesque & Dipaolo, 1989). Previous research showed that although selleck chemicals HAL treatment alone increased D2High availability (Samaha et al., 2007; Seeman, 2009), when paired with AMPH, HAL reduces by 60% AMPH-elevated D2High receptors (Seeman, 2009). One could speculate that different levels of circulating estrogen might influence the affinity state of DA D2R such that increased levels of estrogen might result in a shift in DA D2R affinity from its high state into a low one. This could potentially explain how E2 enhances the behavioural effects of HAL. Future studies should investigate the potential effects of estrogen replacement on the state of the DA D2R in the striatum of sensitized rats. On the other hand, such a postsynaptic

mechanism may not explain how E2 affects the NAcc DA response to HAL. We have evidence that E2 affects D2R autoreceptors in the dorsal PFT�� striatum such that autoreceptor function is less sensitive in high E2 rats (Hussain et al., 2013). This effect may be direct via estrogen receptors; our recent findings show that both ERα (estrogen receptor alpha) and GPER-1 (g-protein-coupled estrogen receptor 1) HSP90 are indeed located on DA terminals in the NAcc (Almey, A., Milner, T.A. & Brake, W.G., unpublished

observations), although we have previously shown that this is not the case in the dorsal striatum (Almey et al., 2012). Thus, E2 may be acting at both pre- and postsynaptic sites in the NAcc to modulate the effects of HAL, and possibly via different mechanisms. HAL became effective only in AMPH-sensitized rats receiving high E2 replacement, and only with prolonged treatment. These data mirror previous research on humans, where estrogen, when added to antipsychotic treatment, significantly reduces schizophrenic symptoms (Kulkarni et al., 1996, 2001; Akhondzadeh et al., 2003). In addition, the neurochemical analysis points at a direct link between NAcc DA availability and E2 levels, whereby locomotor activity in response to AMPH seems to be at least in part driven by this relationship. Although earlier studies have shown that estrogen replacement significantly increased postsynaptic striatal DA levels, as well as AMPH-induced stereotypy (Hruska et al.

cholerae RC385,

TMA21 and MZO-3 yielded expected amplification patterns. In addition, seven carried the V. cholerae RC385 VSP-II (Table 3). Among these, two were isolated from Chesapeake Bay, MD, the same location as V. cholerae RC385, and one also carried a new variant of VSP-I (Grim et al., 2010). Of the remainder, one was isolated from a sewage sample collected in Brazil, one was from Czechoslovakia, two were from Japan and one was from Bangladesh. It should be noted that four of 15 Vibrio mimicus strains were also positive for the V. cholerae RC385 VSP-II variant. Interesting results emerged from screening buy Navitoclax of the collection of V. cholerae isolates from two cholera-endemic sites in Bangladesh, collected from

2004 to 2007. Among the clinical V. cholerae O1 El Tor, a total of 96 carried the V. cholerae CIRS101 VSP-II variant and only one harbored the typical seventh pandemic VSP-II (Table 3). Moreover, three isolates did not contain VSP-II and one was positive for V. cholerae RC385 VSP-II (Table 3), which was negative for VSP-I and ctxA (Grim et al., 2010). A similar result was obtained for environmental V. cholerae O1 isolates, because these were all ctx- and tcpA-positive strains and therefore likely related to the clinical strains. That is, all carried V. cholerae selleck CIRS101 VSP-II, except one strain, which did not have V. cholerae VSP-II or VSP-I (Table 3) (Grim et al., 2010). In contrast, all V. cholerae O139, both clinical and environmental, contained the canonical seventh pandemic VSP-II (Table 3), suggesting that this serogroup is genetically isolated from the dominant V. cholerae O1 pandemic clones. Among V. cholerae non-O1/non-O139 isolates, 70% did not harbor VSP-II, 26% contained V. cholerae RC385 VSP-II and two contained the V. cholerae TMA21 VSP-II (Table

3), showing that these are the most common variants in the nonepidemic V. cholerae population. Comparative genomic analysis of 23 V. cholerae strains belonging to different serotypes, widely distributed geographically and isolated over an extended period of time, has led to the discovery of three new variants of the VSP-II genomic island. This is remarkable, because VSP-I Thiamine-diphosphate kinase and VSP-II were originally considered to be conserved genetic markers of seventh pandemic V. cholerae (Dziejman et al., 2002; O’Shea et al., 2004). To date, two other examples of sequence variation within V. cholerae VSP-II have been described (Dziejman et al., 2005; Nusrin et al., 2009). Our analysis provides further knowledge of this genomic cluster and its evolution in V. cholerae. From the standpoint of genetic comparison, it is clear that the island has undergone significant genetic rearrangement. Two loci, at the 3′ end of the VC0498 and VC0511, may represent hot spots for recombination events within the conserved genomic backbone of the island.

48th Annual Meeting of the European Association for the Study of the Liver. Amsterdam, The Netherlands. April 2013 [Abstract 101]. 61  Schinazi RF, Bassit L, Clayton MM et al. Evaluation of single and combination therapies with tenofovir disoproxil fumarate and emtricitabine in vitro and in a robust mouse model supporting high levels of hepatitis B virus replication. learn more Antimicrob Agents Chemother 2012; 56: 6186–6191. 62  Avihingsanon

A, Lewin SR, Kerr S et al. Efficacy of tenofovir disoproxil fumarate/emtricitabine compared with emtricitabine alone in antiretroviral-naïve HIV-HBV coinfection in Thailand. Antivir Ther 2010; 15: 917–922. 63  Liaw YF, Sheen IS, Lee CM et al. Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, see more and entecavir in patients with decompensated chronic hepatitis B liver disease. Hepatology 2011; 53: 62–72. 64  Dore GJ, Cooper DA, Pozniak AL et al. Efficacy of tenofovir disoproxil fumarate in antiretroviral therapy-naive and -experienced patients coinfected with HIV-1 and hepatitis B virus. J Infect Dis 2004; 189: 1185–1192. 65  Polsen J, Lee WM. AASLD position paper: the management of acute liver failure. Hepatology 2005; 41: 1179–1197. 66  Kumar M, Satapathy S, Monga R et al. A randomized controlled trial of lamivudine to treat acute hepatitis B. Hepatology 2007; 45: 97–101. 67  Yu JW, Sun LJ, Zhao YH, Kang P, Lil SC. The study of efficacy of lamivudine

in patients with severe acute hepatitis B. Dig Dis Sci 2010; 55: 775–783. 68  Yu JW, Sun LJ, Yan BZ, Kang P, Zhao YH. Lamivudine treatment is associated with improved survival in fulminant hepatitis B. Liver Int 2011; 31: 499–506. 69  Miyake Y, Iwasaki Y, Takaki A et al. Lamivudine treatment improves the prognosis of fulminant hepatitis B. Intern Med 2008; 47: 1293–1299. 70  Akhan S, Sayan M. HIV and acute HBV infection: First case report from Kocaeli, Turkey. Hepatol Int 2012; 6: 134. 71  Ikeda-Kamimura M,

Horiba M. Seroconversion of acute hepatitis B by antiretroviral therapy in an HIV-1 infected patient. Protein tyrosine phosphatase Acta Gastroenterol Belg 2010; 73: 389–391. 72  Sagredo S, Mancilla C, Estuardo N, Poniachik J. Fulminant hepatic failure by hepatitis B virus in a patient with human immunodeficiency virus infection. Report of one case. [In Spanish]. Rev Med Chil 2011; 139: 1336–1339. 73  Schirmer P, Winters M, Holodniy M. HIV-HBV vaccine escape mutant infection with loss of HBV surface antibody and persistent HBV viremia on tenofovir/emtricitabine without antiviral resistance. J Clin Virol 2011; 52: 261–264. 74  Jochum C, Gieseler RK, Gawlista et al. Hepatitis B-associated acute liver failure: immediate treatment with entecavir inhibits hepatitis B virus replication and potentially its sequelae. Digestion 2009; 80:235–240. 75  De Socio GV, Mercuri A, Di Candilo F, Baldelli F. Entecavir to treat severe acute hepatitis B.

Also, Google and PubMed searches were conducted using combinations of searching keywords “Malaysia,”“jellyfish,”“Irukandji,”“fatal,” and “near fatal. Where possible, diagnoses of “chirodropid box jellyfish sting” and “Irukandji syndrome” were made by standard clinical definitions previously used in this journal.2 Three fatalities from jellyfish stings were reported in Malaysia since 2000 (locations shown in Figure 1). A 45-year-old Swedish female tourist died after being stung by a jellyfish while taking an evening swim off a beach in Langkawi. She suddenly

shrieked with pain and became unconscious within seconds. Lesions, reportedly consistent with a chirodropid sting, were visible on her legs. She was immediately taken ashore where cardiopulmonary resuscitation (CPR) was commenced. Her husband reported that an ambulance arrived 15 minutes later and the paramedics confirmed that she had been stung by a jellyfish.12 An 8-year-old South Gefitinib solubility dmso Korean girl was reported to have died after a jellyfish sting at Palau Sapi, near Kota Kinabalu, Sabah. She had lesions on both legs and collapsed within check details seconds and died shortly thereafter.10 The lesions described were consistent with chirodropid lesions (photograph not available). However, photographs of lesions on another

child at Palau Sapi 1 month later showed a pattern typical of a multi-tentacled box jellyfish, indicating that chirodropid jellyfish occur in the area.11 A 26-year-old male tourist from Brunei reportedly died after a jellyfish sting at Palau Pangkor. He and several friends were stung and he collapsed and died on the way to hospital. The death was reported to be from an “anaphylactic reaction” to the sting.9 A 44-year-old female British Pregnenolone tourist. The wound (Figure 2), together with the accompanying description, is typical of a chirodropid envenomation, such as from Chironex

spp. The sea was calm, there were high tides, and the water was cloudy. As the victim walked from the sea she felt a light gripping sensation to her lower legs and knees. Within seconds she could not breathe or talk properly, and felt unwell. Transparent blue/gray/purple tentacles were stuck to her lower legs. After staggering a few meters she fell onto the sand, overcome by severe leg pains. Briefly everywhere felt painful, and then localized to excruciating pains in her lower legs. She reported dyspnoea and had a sore (not tight) chest. There was a period of altered (reduced) consciousness, after which she again became aware of leg pains and noticed the lifeguards applying ice. Sitting up caused a feeling of faintness. When told she had been stung by a box jellyfish she expressed disbelief as she had no warning of their potential presence (although a lifeguard later told another tourist that they occurred there). She elected to return to her hotel rather than hospital but had to be taken by wheelchair, as she could barely walk.

001). The percentage of new prescriptions from physician extenders remained relatively constant across periods for all five medications. Seventy-to-eighty per cent of all new target medication prescriptions were from ID clinics,

10% from primary care clinics and 10% from other clinics (data not shown; P<0.001). From March 2003 until December 2007, 49% of all HIV-infected veterans who were prescribed antiretrovirals were in the Southern USA, 20% were in the West, 18% were in the Northeast, and 13% were in the Northcentral (Fig. 3). Significant shifts in prescribing by region over time occurred for Enzalutamide clinical trial all target antiretrovirals. Lopinavir/ritonavir and atazanavir had earliest uptake in the West but by period 3 new prescribing had increased in

the South, closely matching prescribing of all antiretrovirals (P<0.001). Tipranavir had a similar pattern, with greatest early uptake in the West and much less uptake in the Northeast – a pattern that reversed over time (P=0.001). Darunavir had greatest initial uptake in the South but over time uptake increased in the Northeast and Northcentral regions and decreased in the South (P=0.03). Tipranavir and darunavir were FDA approved for use in treatment-experienced patients; hence, <2% of veterans prescribed these agents in any quarter were antiretroviral-naïve (data not shown). Of veterans who received atazanavir in the first two quarters post-approval, 2% Orotidine 5′-phosphate decarboxylase were antiretroviral naïve compared with 9% of veterans who received it in later quarters after approval (P<0.001). Of providers prescribing any antiretrovirals within the VHA, the proportion that prescribed selleck products each target medication rose quickly over the first five-to-six

quarters and then plateaued (e.g. atazanavir) or declined (e.g. tipranavir) (Fig. 4). In the first quarter post-approval, <5% of all antiretroviral prescribers wrote prescriptions for the target medications. By the eighth quarter, however, nearly 30% of all providers prescribing any antiretrovirals within the VHA were prescribing atazanavir in a pattern matching that of lopinavir/ritonavir. For the other target medications, regardless of duration of follow-up, <10% of antiretroviral prescribers were prescribing these agents in any quarter. On average, in any quarter approximately 3750 VHA providers prescribed an antiretroviral. The peak number and percentage of providers prescribing atazanavir occurred in quarter 14 post-approval, with 1189 out of 3702 providers (32.1%) prescribing atazanavir. For darunavir, the number of providers was still increasing at the end of the study period, with 334 out of 3848 providers (8.7%) prescribing darunavir in quarter 6 (the last complete quarter for which data are available). The peak number of providers prescribing tipranavir occurred in the fifth quarter, with 171 out of 3654 providers (4.

When an infant has been started on triple-combination PEP because the maternal VL is >50 HIV RNA copies/mL at 36 weeks and subsequently a delivery maternal VL is <50 HIV RNA copies/mL, then it is reasonable to simplify the infant PEP to monotherapy. Most neonates born in the UK to mothers known to have HIV will be exposed to ART in utero, during delivery and after birth for the first 4 weeks of life. The range of cARTs to which neonates are being exposed in utero continues to increase. Neonatal drug metabolism is generally slower than that of older infants or children and premature neonates have even less efficient metabolism. Owing to a lack of neonatal pharmacokinetic

GW-572016 concentration and efficacy studies and suitable formulations, ART dosing regimens remain restricted to a small proportion of the ARV buy Palbociclib drugs currently manufactured (Table 1). Small pharmacokinetic studies have been performed (zidovudine [24], lamivudine [[25],[26]], tenofovir [11], emtricitabine [27]) and dosing regimens are available for most of the nucleoside analogues and for abacavir from age 1 month [28], while limited study of didanosine in neonates suggests that the pharmacokinetics are highly

variable [9]. The pharmacokinetics of nevirapine in neonates has been described in more detail [[6],[7],[29][[30][#[31]]Ent]267]. Pharmacokinetic-supported dosing is available for the PIs nelfinavir [25] and ritonavir-boosted lopinavir (based on HIV-1 infected infants initiating therapy in

the first 6 weeks of life) [[32][[33][#[34]]Ent]270] and a study that included Montelukast Sodium some infants treated from birth [35]. However, evidence of adrenal suppression has been documented in some neonates treated with lopinavir/ritonavir, particularly when preterm [36], in addition to case reports of cardiac, renal and neurological toxicity, especially in, but not restricted to, premature infants, and including one death during PEP with lopinavir/ritonavir [37]. No effects have been observed with maternal lopinavir/ritonavir in the absence of neonatal dosing. It remains unclear whether these effects are related to lopinavir/ritonavir specifically or could be seen with other ritonavir-boosted PIs. The Writing Group therefore recommends that this PI should be avoided in routine infant PEP and should only be prescribed to preterm neonates in exceptional circumstances. Its use should only be considered after seeking expert advice and where there is multidrug resistance. Close metabolic monitoring in hospital should be undertaken. Nelfinavir, the only other PI with an infant-dosing regimen, will be withdrawn in the near future and will no longer be available for prescription in the UK or elsewhere in Europe. See the CHIVA website for dosing updates (http://www.chiva.org.uk). In contrast to the PIs, nevirapine efficiently crosses the placenta (see below) and is well absorbed by the neonate [38].

The purpose of

this study was to test, in aging, how these neural mechanisms are solicited in the context of visual selective attention processing when task demand is manipulated. We compared young and older adult participants’ behavioral and cerebral patterns in a context of selective attention, with the aim of addressing two main questions. (i) What patterns of activation characterize the elderly individuals? Do they show more bilateral patterns of activation, as in the HAROLD phenomenon (Cabeza, 2002), or more frontal activation, as in the PASA phenomenon (Dennis & Cabeza, 2008), as the task becomes more demanding? For the Ruxolitinib chemical structure HAROLD phenomenon, the characteristic age-related pattern will be an inter-hemispheric-based reorganization whereas there will be an intra-hemispheric reorganization if the PASA phenomenon prevails. Are the HAROLD and PASA phenomena complementary responses for coping with increasing task demand in the aging brain? (ii) What mechanisms of cognitive reserve underlie the age-related pattern? Do older adults cope with increased complexity by recruiting the same regions as younger ones (neural reserve) or by recruiting different sets of brain areas (neural compensation)? In agreement

with the neural reserve hypothesis, the patterns see more of overactivation observed in the older subjects would be ‘equivalent’ to those found when the younger brain contends with increased task Benzatropine demand, that is, for younger subjects in the high-load condition. However, in line with the compensation hypothesis, we expected that older subjects would recruit compensatory sets of brain areas not used by young subjects to compensate for the limited recruitment of specific regions in aging. In order to explore these questions, this series of experiments focused on the nature of the brain reorganization (interhemispheric vs. intrahemispheric) in the context of visual selective attention

and based on the cognitive reserve model to differentiate the underlying mechanisms (neural reserve vs. neural compensation). The purpose of theses studies was to investigate to what extent and how neural reserve and neural compensation contribute to coping with normal aging in two contexts of visual selective attention: simple perceptual processing (i.e. letter-shape matching task: e.g. A-A) and more complex naming processing (i.e. letter-name matching task: e.g. a-A). In both studies, the cognitive demand was also manipulated by varying the attentional load related to the number of stimuli to be processed (low, three letters vs. high, five letters). Taken together, the results of the two studies suggest that the neural mechanisms of cognitive reserve, i.e.

The purpose of

this study was to test, in aging, how these neural mechanisms are solicited in the context of visual selective attention processing when task demand is manipulated. We compared young and older adult participants’ behavioral and cerebral patterns in a context of selective attention, with the aim of addressing two main questions. (i) What patterns of activation characterize the elderly individuals? Do they show more bilateral patterns of activation, as in the HAROLD phenomenon (Cabeza, 2002), or more frontal activation, as in the PASA phenomenon (Dennis & Cabeza, 2008), as the task becomes more demanding? For the selleckchem HAROLD phenomenon, the characteristic age-related pattern will be an inter-hemispheric-based reorganization whereas there will be an intra-hemispheric reorganization if the PASA phenomenon prevails. Are the HAROLD and PASA phenomena complementary responses for coping with increasing task demand in the aging brain? (ii) What mechanisms of cognitive reserve underlie the age-related pattern? Do older adults cope with increased complexity by recruiting the same regions as younger ones (neural reserve) or by recruiting different sets of brain areas (neural compensation)? In agreement

with the neural reserve hypothesis, the patterns GW-572016 of overactivation observed in the older subjects would be ‘equivalent’ to those found when the younger brain contends with increased task those demand, that is, for younger subjects in the high-load condition. However, in line with the compensation hypothesis, we expected that older subjects would recruit compensatory sets of brain areas not used by young subjects to compensate for the limited recruitment of specific regions in aging. In order to explore these questions, this series of experiments focused on the nature of the brain reorganization (interhemispheric vs. intrahemispheric) in the context of visual selective attention

and based on the cognitive reserve model to differentiate the underlying mechanisms (neural reserve vs. neural compensation). The purpose of theses studies was to investigate to what extent and how neural reserve and neural compensation contribute to coping with normal aging in two contexts of visual selective attention: simple perceptual processing (i.e. letter-shape matching task: e.g. A-A) and more complex naming processing (i.e. letter-name matching task: e.g. a-A). In both studies, the cognitive demand was also manipulated by varying the attentional load related to the number of stimuli to be processed (low, three letters vs. high, five letters). Taken together, the results of the two studies suggest that the neural mechanisms of cognitive reserve, i.e.