Case notes of women attending the clinics from 1 January to 30 June 2009 were reviewed. When data were incomplete, women were prospectively interviewed. Case notes of 605 women were reviewed; 478 women had 1107 children. The majority of women (386; 81%) were of Black African ethnicity. Sixty-one per cent (675 of 1107) of the children were known to have been tested for HIV. The children resident abroad were more likely to be untested compared with those resident in the

UK; 186 of 255 (73%) vs. 246 of 852 (29%). A quarter (106 of 432) of the untested children were ≤18 years old; 49 (46%) of these were resident in the UK. The most common reason given by the mothers for not testing was a perceived ‘unlikely risk’. A significant number of children at risk p53 inhibitor of vertically transmitted HIV infection, including 49 children ≤18 years and resident in the UK, were identified through this study. The mothers are being encouraged to have these children tested and a multidisciplinary selleck chemicals team involving adult and paediatric HIV healthcare professionals has been set up to negotiate and facilitate testing. There are several cases of children vertically infected with HIV presenting at older ages in the UK [1]. These children may present with advanced HIV infection [2,3], and thus early diagnosis is important, enabling appropriate treatment to be initiated and potentially leading to improved health outcomes. The early diagnosis of these children is also important

in reducing horizontal transmission as these young people become sexually active. The children of women with HIV infection are at increased risk of being infected and are a potentially accessible group for target testing. In December 2008, the British HIV Association (BHIVA), Children’s HIV Association of the UK and Ireland (CHIVA) and British Association for Sexual Health and HIV (BASHH) issued a consensus document ‘Don’t forget the children’, giving guidance on HIV Idoxuridine testing of children born to HIV-positive women. This states that ‘the HIV status of all the children of known HIV-positive adults in the UK should be known as a matter of clinical urgency’ [4]. There are few data available on the number

of children of HIV-positive women that have yet to be tested for HIV infection. A recent BHIVA audit of 143 UK adult HIV clinics showed that only 61 (43%) had started or completed a review of their patients to identify and test children for HIV infection. In an earlier study of women with HIV infection attending a clinic in south-east England, 51% of their children under 16 years old living in the UK and 91% living abroad were untested [5]. This study looked at the HIV testing status of children whose mothers attend HIV services at three south-west London clinics. It is a statutory duty in England under the Children Act 1989 for healthcare professionals to safeguard children up to the age of 18 years. Hence this study focuses on untested children aged 18 years and younger.

14,19 Treatment strategies for GAE will include combinations of critical care techniques to reduce increased ICP, craniotomy for biopsy or excision of mass lesions, and combination pharmacotherapy with antifungals, anti-protozoal agents, synergistic antibiotics, and several experimental therapies that have shown promise in vitro, such as phenothiazines. Although case fatality rates in GAE are very high (90%–94% in acanthamoebiasis and ≥90% in balamuthiasis), successful drug treatment combinations in acanthamoebiasis have included intravenous pentamidine isethionate, flucytosine (5-flurocytosine), amphotericin B, the benzimidazole

antifungals (albendazole), the triazole antifungals (itraconazole and fluconazole), the synergistic antibiotics, rifampin and trimethroprim/sulfamethoxazole (TMP/SMX) (or amikacin or oral sulfadiazine), and topical ketoconazole PLX-4720 mouse or miltefosine for skin ulcers.26,34–37 In 2008, Aichelburg and colleagues in Vienna reported treating a patient successfully with disseminated tuberculosis and acanthamoebiasis

find more with topical and oral miltefosine, a phosphocholine analog used to treat visceral leishmaniasis, and a combination of intravenous fluconazole, TMP/SMX, synergistic antibiotics (amikacin), and four tuberculostatic drugs.22 Successful intravenous drug treatment combinations in balamuthiasis have included azoles (albendazole, fluconazole, or itraconazole), flucytosine, pentamidine, sulfadiazine, and synergistic macrolide antibiotics (azithromycin or clarithromycin) (-)-p-Bromotetramisole Oxalate and phenothiazines (thioridazine or trifluoperazine).29,31 In 2004, Schuster and Visvesvara demonstrated that the phenothiazines demonstrated in vitro efficacy against B mandrillaris in clinical specimens.34 The optimum duration of drug therapy for GAE is unknown, but most survivors have been treated for many weeks to months.29–31,35–37 In 2010, Martinez and coworkers reported the successful treatment of B mandrillaris-confirmed GAE in a patient with extensive cutaneous and neurological

involvement with prolonged therapy with albendazole, fluconazole, and miltefosine.38 A genetic predisposition to B mandrillaris GAE has now been identified in American Hispanics, who appear less able to produce effective antibodies against the free-living amebae, and may be predisposed by more frequent contact with Balamuthia-contaminated soils and aerosols in agricultural occupations.39,40 Prevention and control strategies for GAE should include (1) consideration of GAE in organ transplant and immunocompromised patients with encephalitis and skin ulcers not improving with standard therapies; (2) recognition of genetic risk factors for acanthamoebiasis and balamuthiasis in Hispanics less able to produce antibodies against causative free-living amebae; and (3) recognition of other soil or stagnant freshwater risk factors in both immunocompetent and immunosuppressed patients with skin ulcers and unexplained meningoencephalitis.

When CB1Rs were blocked in WIN55,212-2 treated newborns, persistent hyperventilation was still observed, which could partly be explained by a perturbation of the central respiratory network. In fact, in vitro medullary preparations from WIN55,212-2 treated pups, free of

peripheral or of supramedullary structures, showed an altered fictive breathing frequency. In conclusion, the endocannabinoid pathway at birth seems to modulate breathing and protect the newborn against apnoeas. However, when exposed prenatally to an excess of cannabinoid, the breathing neuronal network in development seems to be modified, probably rendering the newborn more vulnerable in the face of an unstable environment. “
“It has been reported NVP-BGJ398 price that the hippocampus is very susceptible to methamphetamine (METH) and that neuropeptide Y (NPY) is an important neuroprotective agent against hippocampal excitotoxicity. However, there is very little information regarding the role of the NPYergic system in this brain region under conditions of METH toxicity. To clarify this issue, we investigated the role of NPY and its receptors against METH-induced neuronal cell death in hippocampal organotypic slice cultures. Our data show that NPY (1 μm) is neuroprotective in DG, CA3 and CA1 subregions UK-371804 chemical structure via Y2 receptors. Moreover, the selective activation of Y1 receptors

(1 μm [Leu31,Pro34]NPY) partially prevented the toxicity induced by METH in DG and CA3 subfields, but completely blocked its toxicity in the CA1 pyramidal cell layer. Regarding Y2 receptors, its activation (300 nm NPY13–36) completely prevented METH-induced toxicity in all subregions analysed, which involved changes in levels of pro- and anti-apoptotic proteins Bcl-2 and Bax, respectively. Besides neuronal cell death, we also showed that METH triggers a microglial response in the mouse hippocampus which was attenuated by Y2 receptor activation. To better clarify the effect of METH and the NPY system on microglial cells, we further used the N9 microglial cell line. We found that both NPY and the Y2 receptor agonist were able

to protect microglia against METH-induced cell death. Overall, our data demonstrate that METH is toxic to both neurons and Telomerase microglial cells, and that NPY, mainly via Y2 receptors, has an important protective role against METH-induced cell death and microgliosis. “
“Short-term information retention is crucial for information processing in the brain. It has long been suggested that the hippocampal CA3 region is able to support short-term information retention through persistent neural firing. Theoretical studies have shown that this persistent firing can be supported by abundant excitatory recurrent connections in CA3. However, it remains unclear whether individual cells can support persistent firing.

When CB1Rs were blocked in WIN55,212-2 treated newborns, persistent hyperventilation was still observed, which could partly be explained by a perturbation of the central respiratory network. In fact, in vitro medullary preparations from WIN55,212-2 treated pups, free of

peripheral or of supramedullary structures, showed an altered fictive breathing frequency. In conclusion, the endocannabinoid pathway at birth seems to modulate breathing and protect the newborn against apnoeas. However, when exposed prenatally to an excess of cannabinoid, the breathing neuronal network in development seems to be modified, probably rendering the newborn more vulnerable in the face of an unstable environment. “
“It has been reported check details that the hippocampus is very susceptible to methamphetamine (METH) and that neuropeptide Y (NPY) is an important neuroprotective agent against hippocampal excitotoxicity. However, there is very little information regarding the role of the NPYergic system in this brain region under conditions of METH toxicity. To clarify this issue, we investigated the role of NPY and its receptors against METH-induced neuronal cell death in hippocampal organotypic slice cultures. Our data show that NPY (1 μm) is neuroprotective in DG, CA3 and CA1 subregions Dabrafenib nmr via Y2 receptors. Moreover, the selective activation of Y1 receptors

(1 μm [Leu31,Pro34]NPY) partially prevented the toxicity induced by METH in DG and CA3 subfields, but completely blocked its toxicity in the CA1 pyramidal cell layer. Regarding Y2 receptors, its activation (300 nm NPY13–36) completely prevented METH-induced toxicity in all subregions analysed, which involved changes in levels of pro- and anti-apoptotic proteins Bcl-2 and Bax, respectively. Besides neuronal cell death, we also showed that METH triggers a microglial response in the mouse hippocampus which was attenuated by Y2 receptor activation. To better clarify the effect of METH and the NPY system on microglial cells, we further used the N9 microglial cell line. We found that both NPY and the Y2 receptor agonist were able

to protect microglia against METH-induced cell death. Overall, our data demonstrate that METH is toxic to both neurons and Phosphoprotein phosphatase microglial cells, and that NPY, mainly via Y2 receptors, has an important protective role against METH-induced cell death and microgliosis. “
“Short-term information retention is crucial for information processing in the brain. It has long been suggested that the hippocampal CA3 region is able to support short-term information retention through persistent neural firing. Theoretical studies have shown that this persistent firing can be supported by abundant excitatory recurrent connections in CA3. However, it remains unclear whether individual cells can support persistent firing.

A 23-item survey was Ku-0059436 administered to all students enrolled in each year of the 4-year pharmacy undergraduate programme, University of Sydney, Australia. Perceptions of research in general were measured with four items on a five-point semantic-differential scale and attitudes towards PPR with19 items on a five-point Likert scale. In total 853 students responded to the survey (83% response rate). While students perceived research to be necessary, they found it difficult and were divided in their interests in pursuing research. Attitudes towards PPR were assessed within five identified domains: ‘role of PPR in the curriculum’, ‘engaging in PPR

activities’, ‘confidence to do PPR’, ‘faculty involvement of students in PPR’ and ‘role of PPR in the profession’. Most participants agreed that PPR played an important part in the profession and curriculum but almost half of the cohort lacked confidence to undertake PPR, with very few holding positive attitudes towards all five domains. The PPR instrument was found to be valid SGI-1776 chemical structure and reliable. There were significant differences in perceptions and attitudes at various stages of the degree. Future research should investigate changes in perceptions and attitudes in a single cohort over the 4-year degree, explore factors influencing attitudes

and identify strategies for stimulating research interest. “
“Objectives The aim was to identify local organisational factors that affect sustained delivery of the first Danish publicly reimbursed cognitive service, the Inhaler Technique Assessment Service (ITAS). The ITAS is a 10-min interactive counselling session during which pharmacy staff

assess the inhalation technique of individual asthma patients Tau-protein kinase at the pharmacy counter, and correct any errors. Knowledge of how the organisation of a local pharmacy influences ITAS provision will be used to develop quality indicators as part of a targeted quality-assurance system to support the sustainability of the service in all Danish community pharmacies. Methods Qualitative methods included field observations, semi-structured interviews, group interviews and the collecting of documentary material. Data-source and method triangulation were applied. Seven pharmacies were included in the study. A cross-case analysis compared pharmacies with sustained and reduced numbers of services based on three selected themes: administration of the ITAS, leadership interventions and professional values of pharmacy owner and staff. Key findings Pharmacies with sustained delivery had introduced systematic evaluations of the local delivery of the ITAS and made ongoing efforts to improve staff competencies.

Professor Saye Khoo has received lecture and consultancy fees from Abbott, Gilead and ViiV. Professor Clifford Leen has received consultancy fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Janssen and Merck Sharp and Dohme. STA-9090 order His department has received research awards from Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Janssen and ViiV. Dr Fiona Lyons has no conflicts of interest to declare.

Mr Neal Marshall has received lecture and consultancy fees from Abbott, Bristol-Myers Squibb, Janssen and ViiV. Dr Mark Nelson has received lecture fees from Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Merck Sharp and Dohme, Tibotec and ViiV and consultancy fees from Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Idenix, Merck Sharp and Dohme, Pfizer, Tibotec, and ViiV. His department has received research grants from Abbott, Aspen Pharmaceuticals, Bristol-Myers Squibb, Gilead, Merck Sharp and Dohme, Tibotec and ViiV. Dr Chloe Orkin has received lecture fees from Abbott, Boehringer-Ingelheim, Palbociclib Bristol-Myers Squibb, Gilead, GSK, Janssen, Merck Sharp and Dohme, Pfizer, Tibotec and ViiV. She has received consultancy fees from Abbott, Boehringer

Ingelheim, Bristol-Myers Squibb, Gilead, GSK, Janssen, Merck Sharp and Dohme, Pfizer, Tibotec and ViiV. Her department has received research grants from Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GSK, Janssen, Merck Sharp and Dohme, Pfizer, Tibotec and ViiV. Dr Nicholas Paton’s department has received research grants from Abbott and Merck Sharp and Dohme. Professor Andrew Phillips has received consultancy

fees from Bristol-Myers Squibb, Gilead, GSK Bio, Johnson and Urease Johnson, Merck Sharp and Dohme and ViiV and his department has received research grants from Bristol-Myers Squibb. Dr Frank Post has received lecture fees from Bristol-Myers Squibb, Gilead, Merck Sharp and Dohme, Tibotec/Janssen and ViiV/GSK and his department has received research grants from Gilead and ViiV. Dr Anton Pozniak has received lecture and consultancy fees from Boehringer Ingelheim and Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp and Dohme and ViiV and conference support from Bristol-Myers Squibb and Merck Sharp and Dohme. Professor Raffi has received research funding or honoraria from or consulted for Abbott, Avexa, Boehringer-Ingelheim, Bristol-Myers Squibb, Ferrer, Gilead, Janssen, Merck Sharp and Dohme, Pfizer, Roche, Schering-Plough, ViiV Healthcare. Professor Caroline Sabin has received lecture and consultancy fees from Abbott, Bristol-Myers Squibb, Gilead, and Janssen. Mr Roy Trevelion has no conflict of interests to declare. Dr Andy Ustianowski has received lecture and consultancy fees from Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Merck Sharp and Dohme, Janssen and ViiV and his department has received research grants from Abbott.

In settings of year-round malaria transmission where most adults are semi-immune to malaria, the incidence of parasitaemia and clinical malaria are increased in individuals with HIV infection

[5]. Malaria presents non-specifically with fever, headache, arthralgia, myalgia, diarrhoea and sometimes features of bacterial infection. Patients may be severely unwell and hypotensive, requiring intensive care unit (ICU) involvement early in the hospital admission. Other than severity there is no evidence that HIV ABT199 serostatus modifies presentation. Complications of malaria include hyperparasitaemia, acute renal failure, hypoglycaemia, disseminated intravascular coagulopathy, lactic acidosis, fulminant hepatic failure and cerebral malaria [6]. Mortality is still around 20% with higher rates in HIV-seropositive individuals when treated in Africa. Controversy remains concerning the impact of malaria on mother-to-child transmission of HIV but HIV-seropositive women with malaria have an increased incidence of anaemia, infants with low birth weight, prematurity and infant mortality due to malarial parasites

preferentially binding to the placenta [7]. Malaria should be diagnosed in the same way as in HIV-seronegative individuals, using a combination of thick and thin blood films with or without a rapid diagnostic (antigen) test in selleck chemicals HIV-seropositive individuals (category IV recommendation). In practice, this involves considering the diagnosis in anyone with fever who has returned from an endemic area. Falciparum malaria usually presents within 3 months of their return but non-falciparum malaria may recrudesce many years after their return. There is little information on how HIV may modify this but partial immunity may delay the presentation of falciparum malaria. Malaria should be suspected in anyone returning from an endemic area, as the presentation, especially in the semi-immune person, is very variable. Diagnosis is made by a thick and thin blood film although highly sensitive and specific diagnostic dipsticks now exist [8–10]. Thick films (to diagnose

malaria and estimate the percentage parasitaemia) and Amrubicin thin films (for speciation) should be collected on all patients (category IV recommendation) [6]. Rapid diagnostic tests for malaria antigens may be helpful if malaria is suspected but blood films are negative. In HIV-seronegative individuals they are less sensitive but are useful for laboratories with less experience in interpreting malaria blood films [6]. There is limited information on their performance in HIV-seropositive individuals. Current guidelines recommend that any patient considered to be at risk of viral haemorrhagic fever should have a malaria film done under category 3 conditions first [11]. Follow the World Health Organization guidelines [12].

More recently, C. vulgaris NJ-7, a strain isolated from the Antarctic, was used to investigate the adaptation of eukaryotic microbes to permanently cold environments (Hu et al., 2008; Li et al., 2009). The strain NJ-7 possesses the same 18S rRNA gene sequence as that of UTEX259, a strain isolated

from the temperate region, but shows a significantly intensified freezing tolerance (5- to  1000-fold higher viability) than the temperate strain. Comparative studies of the two C. vulgaris strains provide opportunities to understand how intra-species Cabozantinib mw evolution is undertaken in eukaryotic microbes to adapt to the Antarctic or other extreme environments. HIC6 is a group-3 late embryogenesis abundant (LEA) protein found in C. vulgaris. Together with HIC12, it was first identified by 2D-HPLC and SDS-PAGE to be hardening (cold treatment)-induced in the strain C-27 (Honjoh et al., 1995). Its cDNA was also identified by differential screening of a cDNA library (Joh et al., 1995) or suppression subtractive hybridization (Machida et al., 2008). LEA Smad inhibitor proteins were initially found at the late stage of embryogenesis in cotton (Galau et al., 1986) and were subsequently found in algae (such as C. vulgaris), cyanobacteria (Close & Lammers, 1993), nematodes (Browne

et al., 2002) and fungi (Abba’ et al., 2006). The proteins can be divided into different groups on the basis of similarities in amino acid sequences (Colmenero-Flores et al., 1997; Cuming, 2005; Battaglia et al., 2008). Like many other LEA proteins, HIC6 remained soluble under boiling conditions and showed in vitro cryoprotective activities on lactate dehydrogenase (LDH) (Honjoh et al., 2000). Overexpression of HIC6 in plant or yeast could enhance their freezing tolerance (Honjoh et al., 1999, 2001), and

in the transgenic plant, HIC6 was localized to mitochondria (Honjoh et al., 2001). In strains NJ-7 and UTEX259, the encoding gene hiC6 was also induced upon exposure to cold, and the expression was intensified in strain NJ-7 in comparison with UTEX259 (Li et al., 2009). These results suggest that the enhanced expression of hiC6 is probably involved in the development of freezing tolerance in C. vulgaris. The intensified expression of hiC6 in NJ-7 could be due to gene duplication, increased transcription or post-transcriptional regulation. many In our previous study, only one hiC6 gene was identified in each of the two Chlorella strains, NJ-7 and UTEX259 (Li et al., 2009). In the present study, however, sequencing of that chromosomal region revealed that multiple hiC6 genes are organized in tandem in both strains. The tandem-arrayed genes encode different HIC6 isoforms and are differentially expressed. Chlorella vulgaris strains were grown in BG11 (Stanier et al., 1971) in the light of 50 μE m−2 s−1 at 20 °C with aeration. Cells grown at 20 °C were cooled to 4 °C in a water bath and transferred to a 4 °C refrigerator with aeration and illumination (50 μE m−2 s−1) for different periods of time.

The cold shock response is highly conserved amongst bacteria with Csps as well as PNPase also contributing to the cold selleck chemicals shock response in other species such as Yersinia and Bacillus (Palonen et al., 2010). The enteric pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) is closely related to E. coli. It is a successful pathogen capable of infecting both warm-blooded and poikilothermic animals

including fish, nematodes, amoebas and plants (Lewis, 1975; Van der Walt et al., 1997; Charkowski et al., 2002; Cooley et al., 2003; Tenor et al., 2004; Doyel & Beuchat, 2007; Onyango et al., 2009). Hence, S. Typhimurium is also expected to experience wide fluctuations in environmental temperature. Both pnp and csdA (the latter also termed deaD) are closely linked on the genome of S. Typhimurium and only separated by nlpI that encodes for a membrane lipoprotein (Blattner et al., 1997; Ohara et al., 1999; McClelland et al., 2001; Parkhill et al., 2001; Nie et al., 2006). We have previously shown that pnp and nlpI have opposing effects on biofilm formation at decreased growth temperatures with PNPase and NlpI, respectively, enhancing and suppressing biofilm formation (Rouf et al., 2011). As nlpI is positioned between pnp and csdA, we have here investigated the contribution of pnp, nlpI and csdA (the latter hereafter referred to as deaD) in the cold

acclimatization response in S. Typhimurium. Our data show that pnp and nlpI constitute an operon that is transcriptionally separate from deaD and that PNPase, NlpI and DeaD individually Ku-0059436 in vitro contribute to the growth of S. Typhimurium at 15 °C. Our findings thereby define a new role for NlpI in bacterial cold acclimatization. Bacterial strains and plasmids are listed in Table 1. Bacteria were grown in Luria–Bertani medium (LB). Antibiotics (Sigma) Liothyronine Sodium were used where appropriate including ampicillin, 100 μg mL−1; chloramphenicol, 10 μg mL−1; kanamycin, 30 μg mL−1; and tetracycline, 10 μg mL−1. For induction of recombinant NlpI, media were supplemented with 0.1% L (+)-Arabinose (Sigma). Salmonella

enterica serovar Typhimurium SR-11 mutants (∆pnp, ∆nlpI and ∆deaD) were created by the one-step gene inactivation technique described previously (Datsenko & Wanner, 2000; Rouf et al., 2011). Mutated genes were transferred into S. Typhimurium SR-11 by phage P22 int transduction from S. Typhimurium ATCC 14028 background (Schmieger, 1972). The pnp–nlpI double mutant was constructed in succession. First, the PCR-amplified tetracycline resistance gene from pACYC184 was cloned into the KpnI site at codon 201 of pnp in vector pSU41. Then, the pnp::tet mutation was cloned into the pCVD442 suicide plasmid (Donnenberg & Kaper, 1991) and introduced into S. Typhimurium SR-11. The integrated vector was excised through sucrose selection to generate the pnp* mutant strain MC55.

4 Hz in young rats and 53.5 Hz in aged rats (Insel et al., 2012), and this difference was statistically reliable. Because gamma frequencies are thought

to be mediated by network interactions between glutamatergic and GABAergic cells (Tiesinga et al., 2001; Börgers et al., 2005; Wang, 2010), the changes in gamma frequency suggest that the interaction between these cell types may be compromised in aged animals. In support of this, Insel et al. found that, during the performance of the task, putative excitatory and inhibitory neurons of the medial PFC fired preferentially at different phases of the gamma cycle in young and aged rats. When cross-correlation analysis was applied to simultaneously recorded excitatory–inhibitory cell pairs, the interval between the excitatory drive onto Cyclopamine molecular weight inhibitory cells was lengthened in the older rats (Insel et al., 2012). While arguments for direct causation cannot be made, these studies suggest that GABAergic transmission is altered in the PFC of aged rodents and that this may contribute to altered gamma synchrony among medial PFC networks. Converging evidence links age-related working memory impairments to dysfunction of adrenergic systems in primates. Indeed, age-related disinhibition of cyclic adenosine monophosphate (cAMP) signaling has been shown to lead to decreases in persistent firing of area 46 neurons that are active through a delay period during Enzalutamide nmr working-memory

tasks (Ramos et al., 2003; Arnsten et al., 2010; Wang et al., 2011). These delay-firing neurons show a sustained activation that Resminostat lasts for the duration of the cue delay period of a delayed response task (Goldman-Rakic, 1995). This increased activation is modulated by spatial location on a screen, and is greatest for the neurons’ preferred direction. In aged monkeys, there is an age-related loss in response modulation of these neurons to their preferred spatial location during working memory tasks, to a point where

delay neurons show very little increase in firing rate during the cue delay period (Wang et al., 2011). The decrease in activity of delay neurons in aged monkeys could be rescued using local drug administration that inhibited either cAMP or the downstream potassium channels that cAMP is known to activate (HCN, KCNQ; Wang et al., 2011). The same results could be obtained using local infusion of guanfacine, an α2A adrenergic agonist that inhibits cAMP signaling (Wang et al., 2011). Guanfacine and clonidine are both α2A adrenergic agonists known to enhance working memory performance in aged rats (Arnsten et al., 1988; Arnsten & Goldman-Rakic, 1990; Ramos et al., 2003). Because α2A adrenergic agonists have no effects on a visual pattern discrimination task (Arnsten & Goldman-Rakic, 1985), the effect of guanfacine on working memory performance is probably through its action on the activity of PFC neurons.