It is hoped that these mutations will not affect the probability

It is hoped that these mutations will not affect the probability of treatment success on second-line regimens as they are based on a PI coupled with two novel NRTIs to which the patient has not been previously exposed [1]. A number

of studies have provided data consistent with this expectation [8–10]. However, the development of thymidine analogue mutations (TAMs) or other major NRTI mutations has the potential to render these second-line regimens ineffective because of the widespread cross-resistance with other NRTIs [11]. Recent studies have suggested that failing NNRTI-based regimens have a greater susceptibility to the development of NRTI resistance mutations than do boosted PI-based regimens [12,13]. In industrialized countries, see more the increased frequency of these mutations is likely to be of little clinical consequence as regimens can be tailored to the individual resistance mutation profiles. However, whether these mutations would reduce effectiveness of the commonly available second-line regimens in RLSs is unknown. The aim of this study was to examine how the development of

specific drug resistance mutations among individuals on highly active antiretroviral therapy (HAART) could affect the likelihood of treatment success on the second-line regimens that are available in RLSs. The rationale for performing this study in British Columbia (BC), as compared with resource-limited settings, is that PIs are not widely available outside of industrialized countries AZD4547 concentration Protein tyrosine phosphatase and almost never used as first-line therapy [14,15]. This means that such a comparison would be difficult to conduct in these settings. Our primary explanatory variable was the third drug class (boosted PI or NNRTI) included in the participant’s initial ART regimen. The HAART Observational Medical Evaluation and Research (HOMER) study is a prospective observational cohort of all antiretroviral-naïve patients aged 18 years and

older initiating HAART in BC, Canada. It has been described in more detail elsewhere [16,17]. The BC Centre for Excellence in HIV/AIDS (BC CfE) through the Drug Treatment Program distributes antiretroviral drugs free of charge based on specific guidelines generated by the centre’s therapeutic guidelines committee [18]. The guidelines are largely compatible with those of the International AIDS Society–USA panel [19]. Physicians enrolling HIV-infected individuals complete drug request forms, which compile information on the applicant’s address, past HIV-specific drug history, CD4 cell counts, plasma HIV-1 RNA, drugs requested and enrolling physician data. At the time of the first drug refill, participants are asked to provide informed consent for accessing additional medical information, including electronic records. The consent is optional and participants’ refusal to sign it does not limit access to free ART.


Opportunities Cyclopamine ic50 are therefore emerging to comparatively analyse host-invading fungal transcriptomes. In this minireview, we examine the results of recent investigations and ask whether it is possible to

draw exploitable parallels or diversifications among the studies. We consider analyses of three human (Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans) and two plant (Ustilago maydis and Magnaporthe grisea species complex) fungal pathogens (Table 1), giving careful consideration to methodological and technical limitations of the experimentation involved. Six recent studies were included in our analysis. Methodological aspects (e.g. host species, immunosuppression and/or dosing regimens, etc.) of the reported experimentation are detailed in Table 1. Those that characterized host adaptation of the human respiratory pathogens A. fumigatus and C. neoformans (Hu et al., 2008; McDonagh et al., 2008) used mouse inhalational models of pulmonary infection, with subsequent bronchoalveolar lavage (BAL), to examine early-stage host adaptation in harvested fungal elements. Aspergillus fumigatus is a common mould that causes opportunistic invasive

infection Dabrafenib manufacturer in immunocompromised patients (Latge, 1999). To mimic this pathophysiology, mice were chemotherapeutically rendered neutropenic before infection. As A. fumigatus spores are abundant among the airborne microbial communities, and pulmonary infection is usually acquired following spore inhalation, mice were infected via the intranasal route (Fig. 1a), with a saline suspension of freshly harvested mitotic spores. Mice were culled at a time point (14 h) corresponding to the onset of pulmonary tissue invasion (Fig. 1b) and the transcriptome of infecting fungal germlings was analysed, relative to developmentally matched laboratory-cultured

germlings, using doubly amplified mRNA populations. A similar experimental protocol (Fig. 1d and Protein kinase N1 e) was adopted by Hu and colleagues for C. neoformans, with the exception that mice were not immuncompromised, and two time points, 8 and 24 h, were adopted for the harvest of fungal elements. The serial analysis of gene expression (SAGE) methodology (Patino et al., 2002) was used to profile transcript populations from unamplified total RNA, obtained from the pooled contents of 20 murine BALs. SAGE ranks transcript abundance in RNA populations, which, with normalization between samples, can provide information on the relative transcript abundance between transcript populations. Therefore, no direct comparison with a reference sample was performed for this study; rather, the number of SAGE tags identified per transcript was recorded and tag populations were compared with those obtained in previous experimentation. Various infection modelling options exist for Candida species as these organisms cause a range of infectious diseases.

“The Pharmacy Clinical Services Group (PCSG) was formed in

“The Pharmacy Clinical Services Group (PCSG) was formed in 2009. Its aim was to design and deliver a world-class pharmacy service to 250 000 accredited persons and consider the pharmaceutical needs of 9.2 million visitors to the London 2012 Games. The explanatory case study method was used to investigate how the PCSG prepared and how they considered the wider vision of

the Games. The study investigated two propositions: (1) that the PCSG has a communication function and (2) that it has a design function. A range of data were examined using NVivo 9 data management software. The study identified four emerging themes and a number of subthemes. The study validated the propositions and highlighted that the PCSG had a leading role within the wider multidisciplinary team. The study found that the PCSG embraced the wider vision of the Games and was exceptionally well prepared to deliver a world-class pharmacy service, anticipating a check details new gold standard for the provision of pharmacy services for future sporting events. “
“In 2007 Alberta, Canada, became

the first North American jurisdiction to adopt prescribing legislation for pharmacists. In light of these legislative changes and expanded scope of pharmacy practice, we evaluated what ‘prescribing’ means to pharmacists in Alberta and the application of prescribing in pharmacy practice. We invited pharmacists to participate in semi-structured telephone interviews using JNK inhibitors closed and open-ended questions. Pharmacists working in community, hospital or other settings were selected using a mix of random and purposive sampling. Interviews were audiorecorded and transcribed, and data were entered into nVIVO 9 software. Transcriptions were analysed by two investigators using an interpretive description approach to identify themes. Thirty-eight pharmacists were interviewed, of whom 13 had additional (independent) prescribing authorization.

Prescribing had a wide breadth of meaning to the pharmacists in our study, which included writing a new prescription and extending an existing prescription, as well as advising on non-prescription medications. Pharmacists described prescribing in terms of the physical act of writing the prescription and as part of the patient care process as well as the legislated definition of pharmacist prescribing. The sense of increased Roflumilast responsibility associated with prescribing was noted by many pharmacists. Prescribing had diverse meanings to pharmacists in our study, and appeared to be context-specific. Understanding the meaning prescribing holds for individual pharmacists is important to explore whether pharmacist’s definition of this expanded scope has shaped pharmacists’ enactment of prescribing practice. “
“To examine factors influencing the amount of time and information pharmacy personnel provide to patients at drive-through and walk-in counselling areas. On-site observational data collection in 22 community pharmacies by pharmacy students.

Current treatment guidelines recommend first-line HAART regimens

Current treatment guidelines recommend first-line HAART regimens containing a combination of two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) [2]. Mitochondrial toxicity (MtT) has been recognized as one of the most serious potential side effects of NRTI therapy, particularly with the use of the thymidine analogue NRTIs zidovudine

and stavudine (d4T) [3]. Although the clinical manifestations of MtT vary between specific NRTIs, a serious and immediately life-threatening consequence of MtT is symptomatic hyperlactataemia (SHL) and lactic acidosis (LA) [4], often associated with exposure to d4T and didanosine (ddI) [5]. Although infrequent with a reported incidence of three-to-four per 1000 patient-years (py) [6,7], LA is a serious condition associated with significant mortality [4]. SHL without acidosis, although less serious, is more prevalent PLX-4720 clinical trial five of 349 (1.4%) patients were affected in one study [6]. Risk factors for SHL and LA have not been clearly defined, and vary depending on the study and the population exposed. Extremes of body mass index (BMI) [8,9], female gender [5] and lower CD4 T-cell count [5] have been reported to be associated

selleck chemicals llc with LA and SHL. The use of d4T and ddI in developed countries has markedly declined, with reductions in the prevalence of associated toxicities [10]. However, these agents are still commonly used in resource-limited settings, where Thalidomide the largest burden of HIV disease remains. Reports of clinical manifestations of MtT have been increasing in these regions, where there is also a difficulty in diagnosing MtT and a shortage of alternate antiretroviral agents [9,11]. As a result, there is a need for predictors for LA and SHL to identify

those who may be at higher risk. It is presumed that SHL and LA arise from an inability of liver and skeletal muscle to meet aerobic energy requirements secondary to mitochondrial dysfunction [12–14]. However, biopsy of these tissues is invasive and associated with significant risks. In contrast, peripheral blood mononuclear cells (PBMCs) are easier to sample and changes in markers of mitochondrial function such as mitochondrial DNA (mtDNA) and mitochondrial RNA (mtRNA) in PBMCs have been reported with both HIV infection itself and with exposure to HAART [15–17]. This offers the potential for changes in mtDNA and mtRNA in PBMCs to be used as markers of tissue mitochondrial dysfunction, although reports to date have been conflicting. In cross-sectional studies, HIV-infected individuals have been found to have lower PBMC mtDNA copy numbers than HIV-uninfected individuals, and those with SHL to have lower mtDNA copy numbers than untreated HIV-infected controls [15]. However, other cross-sectional studies in HIV-infected subjects have failed to show an association between PBMC mtDNA and current or prior exposure to NRTIs [18] or mtDNA content in tissues such as muscle [19].

The cruise ship passenger death rates declined significantly duri

The cruise ship passenger death rates declined significantly during each year’s third quarter (p = 0.0025; Figure 2). However, the cruise ship passenger death rates increased significantly, from 0.37 to 0.82 deaths per million passenger-nights from year 1 to year 3 (p = 0.0094). The rate of cardiovascular deaths among cruise ship passengers increased significantly from 0.27 to 0.66 per million passenger-nights over the 3-year period (p = 0.0088) and decreased every third quarter (significant seasonality) (p = 0.0055). In contrast, the rate of non-cardiovascular deaths among cruise ship passengers did

not differ significantly by year for years 1 to 3 (range 0.1–0.18 per million passenger-nights). This analysis represents the first comprehensive TGF-beta inhibitor investigation of causes of death among international travelers arriving in the United States on conveyances. Our investigation showed that cardiovascular conditions were the major cause of death for travelers of both sexes. This finding is consistent with an earlier report that the most common cause of death for U.S. travelers abroad in 1975 and 1984 was cardiovascular Raf inhibitor disease.9 From 2005 to 2007, approximately one third of deaths in the U.S. population were attributed to cardiovascular disease (including

stroke).32–34 In contrast, 70% of the deaths in our investigation were attributed to cardiovascular conditions, which is more than twice the proportion of cardiovascular deaths for the U.S. population. Infectious disease caused 12% of the deaths in our investigation, but only one of these deaths, which occurred in an HIV-positive person with pneumococcal pneumonia, may have been preventable by vaccination.35 The other three persons who died from vaccine-preventable diseases (two meningococcal meningitis and one rabies) did not meet the vaccination criteria of the Advisory Committee on Immunization TCL Practices and CDC’s Health Information for International Travel (Yellow Book) and were unlikely to have received these vaccinations before travel.36–40 The male predominance

of deceased travelers reported to CDC is consistent with previous published reports.5,9–11,14–15,20 An analysis of GeoSentinel data from 1997 to 2007 showed that male travelers had a higher risk of acute hepatitis A, chronic viral hepatitis, and sexually transmitted infections (STI).41 Of the males who died from infectious disease in our investigation, one died of disseminated Neisseria gonorrhoeae, one from viral hepatitis, one from chronic hepatitis C, and three from HIV/AIDS complications; no deaths of females were attributed to STIs, hepatitides, or HIV/AIDS. However, male travelers were not more likely to die of infectious disease than female travelers. Sixty-two percent of deaths in our investigation were associated with maritime travel; of these, 85% were associated with cruise ships.

The following guidance considers issues concerning the initiation

The following guidance considers issues concerning the initiation and PD0325901 mouse choice of ART for HIV-positive women who are not currently pregnant. For guidance on the management of pregnancy in HIV-positive woman please refer to the BHIVA guidelines for the management of HIV infection in pregnant women 2012 [1]. There are few specific data on ART treatment in women other than in pregnancy. Data available are largely from a meta-analysis, post hoc analyses or derived from cohort studies. The majority of the randomized

clinical trial data on ART comes from studies that have enrolled mostly male subjects. If RCTs do enrol women, the numbers are often too small to draw significant gender-based conclusions. Approximately one-third of people diagnosed with, and accessing care, for HIV in the UK are women [2]. The majority are of childbearing age but the age range is increasing, adding the complexity of menopause and its sequelae to the management

of HIV-positive women. Many HIV-positive women in the UK are of African heritage and face overlapping challenges to their health and well-being [3]. Women’s experience of HIV reflects multiple social and cultural influences, which when combined with sex-specific biological factors influence individual responses to HIV. We recommend therapy-naïve HIV-positive women who are not pregnant start ART according to the same indicators as in men (see Section 4: When to start) 1A. Proportion of HIV-positive women with CD4 cell count <350 cells/μL

not on ART. Gender differences in HIV VL and CD4 cell count at different stages of infection have been observed [4] but PF-02341066 molecular weight have not been consistently associated with long-term clinical outcomes for HIV-positive women. Based on current data, the indications for starting ART do not differ between Rapamycin women who are not pregnant and men. Gender-specific socio-economic and cultural factors may impact on women’s ability to access care and manage their medication, compromising their ability to initiate and adhere to therapy, and they may require support from the multidisciplinary team. We recommend therapy-naïve HIV-positive women start ART containing two NRTIs and one of the following: PI/r, NNRTI or INI (1A), as per therapy-naïve HIV-positive men. We recommend therapy-naïve HIV-positive women start ART with preferred or alternative NRTI backbone and third agent as per therapy-naïve HIV-positive men (See Section 5.1: What to start: summary recommendations) (1A). Factors such as potential side effects, co-morbidities, drug interactions, patient preference and dosing convenience need to be considered in selecting ART in individual women. We recommend both HIV-positive women of childbearing potential and healthcare professionals who prescribe ART are conversant with the benefits and risks of ARV agents for both the health of the HIV-positive woman and for that of an unborn child (GPP).

We have demonstrated that the reduction in pathogenicity is attri

We have demonstrated that the reduction in pathogenicity is attributable to the detachment of the germlings

on treatment with effective enzymes. In this study, MMPs were confirmed to be useful for protecting wheat from M. oryzae. Such a detachment effect by MMPs was also reported OSI-906 in Alternaria alternata Japanese pear pathotype (Hyon et al., 2009) suggesting universality in filamentous fungi. We also demonstrated biological control for rice blast disease by employing detachment action with gelatinolytic bacteria (Shimoi et al., 2010). Further studies are needed to elucidate the particular substrate(s) of these enzymes in filamentous fungi. We are indebted to Professor Yukio Tosa, Kobe University, for providing M. oryzae (Br48), wheat seeds, and valuable suggestions. This research was supported in part by Grants-in-Aid for Scientific Research B (No. 18380033) and by Grants-in-Aid for Young Scientists B (No. 19780036) from the Japan Society for the Promotion of Science,

and was also supported by The Plant Science Education Unit, Nara Institute of Science and Technology (NAIST), Japan. “
“Phenotype-based Palbociclib mw screening of bacterial metagenomic libraries provides an avenue for the discovery of novel genes, enzymes, and metabolites that have a variety of potential clinical and industrial uses. Here, we report the identification of a functionally diverse collection of antibacterially active enzymes from the phenotypic screening of 700 000 cosmid clones prepared from Arizona soil DNA and hosted in Ralstonia metallidurans. Environmental DNA clones surrounded by zones of growth inhibition in a bacterial overlay assay were found, through bioinformatics and functional analyses, to encode enzymes with predicted peptidase, lipase, and glycolytic Resveratrol activities conferring antibiosis. The antibacterial activities observed in our R. metallidurans-based assay could not be replicated with the same clones in screens using Escherichia coli as a heterologous host, suggesting that the large-scale screening of metagenomic libraries for antibiosis

using phylogenetically diverse hosts should be a productive strategy for identifying enzymes with functionally diverse antibacterial activities. “
“Polyketides and nonribosomal peptides represent two large families of natural products (NPs) with diverse structures and important functions. They are synthesized by polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS), respectively. Lysobacter enzymogenes is emerging as a novel biocontrol agent against pathogens of crop plants and a new source of bioactive NPs, such as antibacterial antibiotic WAP-8294A2 and antifungal antibiotic HSAF. Genome survey of strain OH11, a Chinese L. enzymogenes isolate, detected four novel PKS, NRPS or hybrid gene clusters, designed as cluster A to D.

, 1987a, b) or to Saccharomyces cerevisiae expressing norA or ord

, 1987a, b) or to Saccharomyces cerevisiae expressing norA or ordA after induction with

galactose (Yu et al., 1998). Following a 4-h incubation, metabolites were extracted into methylene chloride and aliquots were examined by TLC. blast searches (tblastx and blastp) were performed against the sequenced fungal genome datasets in Pubmed (, the Broad Institute fungal database (, and the A. flavus genomic sequence ( The cut-off for matches selleck screening library was E−30. Transformation of A. flavus AF13ΔniaD with the linearized norA knockout vector (Fig. 2a) yielded approximately 60 colonies, three of which had

slightly darker orange mycelia when regrown on PDA plates. The three darker orange transformants buy Tamoxifen were confirmed to be double crossover norA disruptants by PCR (Fig. 2b). A 1.5-kb PCR band was obtained for intact norA in the AF13 control strain and an 8 kb product for the positive ΔnorA transformants (Fig. 2b). The latter product is consistent with the size expected with the 7 kb niaD selection marker inserted into the norA gene. Only acetone extracts of the norA knockout cultures and cultures transformed with the selection marker were examined by liquid chromatography combined with mass spectrometry (LC/MS; Fig. 3 and Table 1). A metabolite eluted after AFB1 (14.1 min compared with 13.7 min) and exhibited a blue-shifted (λmax=332 nm) chromophore compared with that of AFB1 (λmax=362 nm). This less polar compound was identified as deoxyAFB1 by its positive ion mass spectrum (M+H=297; deoxyAFB1, M=296 Da) and having a retention time and UV-visible chromophore identical to that of deoxyAFB1 prepared by established synthetic methods (Hsia & Chu, 1977). The LC data showed that deoxyAFB1 accumulated in at least 20-fold greater

amounts in the norA knockout strain than in the selection marker-only transformed strain (Fig. 3). Comparison of other metabolites in the acetone extracts of an AF13ΔnorA clone (#15) and the AF13 control with natural or synthetic standards by UV-visible spectrophotometry and positive ion LC/MS confirmed the presence of OMST (15.9 min), HOMST (12.4 min, M+H=355, M=354), and AFB1 (13.8 min) (Table 1). Endonuclease The metabolites shared identical LC retention times, UV-visible chromophores, and mass spectra with their respective standard. Several unknown compounds were also observed in extracts of fungi with both mutant and intact norA. One exhibited a chromophore (λmax=318 nm, shoulder at 360 nm; M+H=371, M=370) similar to those of OMST and HOMST, suggesting that it could be a related intermediate in the pathway. Two unknown compounds eluting at 10.9 and 13.0 min with the same mass (M+H=329, M=328) were found in extracts from control and norA mutant fungi. One of them eluted at 10.9 and 13.0 min, and exhibited a chromophore similar to that of AFB1 (λmax=360 nm).

pseudintermedius EXI Significant homology was detected with thes

pseudintermedius EXI. Significant homology was detected with these known ETs (38.4–70.4% identity), particularly with SHETB (70.4%), ETD (66.1%) and EXI (56.9%). In addition, the predicted amino acid sequence of the orf possessed the conserved catalytic triad, His-99 (H), Asp-147 (D) and Ser-221 (S), which is known to comprise the active site of S. aureus ETA, ETB and ETD needed to digest Dsg1 (Fig. 1) (Hanakawa et al., 2004). Phylogenic analysis of the ETs revealed that the orf was most similar to SHETB in its primary structure (Fig. 2). To investigate whether

the novel orf gene product conferred exfoliative toxicity in canine skin, purified recombinant protein of the orf product (new ORF) or PBS was injected into the skin of three healthy Beagles. Macroscopically, the novel ORF protein induced skin exfoliation at 24 h postinjection, whereas no selleck inhibitor PLX3397 apparent changes were observed with PBS alone (Fig. 3a and b). The injection site was evaluated histopathologically 12 h after injection. Intraepidermal splitting at the level of the granular layer was observed at the site of injection of the new ORF protein, while no changes were observed at the PBS injection site (Fig. 3c and d). Splitting was also observed in the granular layer of the follicular

infundibulum (data not shown). To determine the effect of the new ORF protein on Dsg1 in canine skin, immunofluorescence analysis of Dsg1 and Dsg3 was performed using cryosections of the canine skin described above. In normal canine skin, Dsg1 is reportedly expressed throughout the entire epidermal layer, while Dsg3 is only expressed in the lower epidermis (Nishifuji et al., 2007). We found that cell surface staining for Dsg1 was abolished in canine skin injected with the new ORF protein, whereas staining was retained in the skin injected with PBS (Fig. 3e and f). In the same area, the cell surface staining for Dsg3 was not altered by the presence or absence of the recombinant toxins (Fig. see more 3g and i). To further investigate the direct degradation

of the extracellular domains of canine Dsg1 by the novel ORF protein, baculovirus cDsg1 and cDsg3 proteins were incubated with the purified ORF protein or PBS alone in vitro. Immunoblot analysis showed that cDsg1, but not cDsg3, was degraded into smaller peptides by the novel ORF protein (Fig. 4). The exfoliative toxicity of the new ORF protein demonstrated in this study, namely the selective digestion of Dsg1, was similar to that seen with previously isolated ETs (Amagai et al., 2000, 2002; Yamaguchi et al., 2002; Fudaba et al., 2005; Nishifuji et al., 2005), including S. pseudintermedius EXI (K. Iyori & K. Nishifuji, manuscript in preparation). The occurrence of the orf gene was determined among Japanese isolates of S. pseudintermedius from the cutaneous lesions of dogs with superficial pyoderma exhibiting various clinical phenotypes and from the nasal cavities of healthy dogs without any skin lesions.

cocaine self-administration) with brain region group as a repeate

cocaine self-administration) with brain region group as a repeated measure. These were followed by planned Bonferroni’s tests for multiple comparisons. Statistical significance was considered

at P < 0.05. Animals self-administered cocaine (1.5 mg/kg per injection) for five consecutive days with a daily maximum of 40 total injections (all animals self-administered the maximum each day). Injections were limited to ensure that all animals had the same intake over each self-administration session to control for total intake as a factor in the functional effects of cocaine. Because of this limit on the number of daily injections, animals quickly reached the maximum total daily intake (60 mg/kg) and could not exceed that. However, animals could control the rate of intake over the sessions ZD1839 research buy (Fig. 1).

Similar to previous studies this rate increased over the 5-day Palbociclib solubility dmso period (Mateo et al., 2005; Calipari et al., 2012; Ferris et al., 2012). One-way anova revealed a main effect of session (F4,56 = 14.93, P < 0.001). Tukey's post hoc analysis revealed an increase in rate vs. the first session on sessions two (q = 4.216, P < 0.05), three (q = 5.843, P < 0.01), four (q = 8.734, P < 0.001) and five (q = 9.673, P < 0.0001). Following cocaine self-administration, behavioral activity was assessed using automated monitors. Our a priori hypothesis was that locomotor activity in response to a novel environment would be reduced following cocaine self-administration (Koeltzow & White, 2003). Two-way anova revealed a main effect of Oxymatrine cocaine self-administration on the response to a novel environment (F1,75 = 4.04, P < 0.05). In addition, there was a main effect of time (F5,75 = 73.53, P < 0.0001) as animals habituated to the activity chamber. There were no significant differences between the groups in either stereotypy or vertical activity. Bonferroni's tests for multiple comparisons were performed

to compare across treatment groups, and a reduction in locomotor activity was observed at the 15-min time point in animals that had undergone cocaine self-administration (t = 3.219, P < 0.05; Fig. 2). Alternatively, we found a significant effect of time (F17,204 = 17.64 P < 0.001), but not of treatment (F1,204 = 0.05, NS) or an interaction (F17,204 = 8.93, NS) on saline-induced locomotion, indicating that normal forward locomotion was not impaired by a prior cocaine self-administration history (Fig. 3). To determine whether other measures of locomotor behavior had changed as a consequence of cocaine self-administration and withdrawal, we assessed vertical activity and stereotypy-like behavior. Student’s t-test revealed that cocaine self-administration animals had higher vertical counts as compared with controls (t12 = 7.604, P < 0.0001; Fig. 4). In addition, cocaine self-administration animals had lower stereotypy counts as compared with controls (t12 = 3.988, P < 0.0001; Fig. 4).