Human Enterovirus Diversity by Next-Generation Sequencing Analysis in Urban Sewage Samples From Buenos Aires Metropolitan Area, Argentina: A Retrospective Study.

Human Enteroviruses (hEVs) are responsible for a wide variety of human diseases. During hEVs infection, virions are excreted in human feces and the fecal-oral route is the primary pathway for person-to-person transmission. Sewage surveillance could help in monitoring hEVs circulation and describing their diversity in a specific population. In this study, sewage samples collected in Buenos Aires Metropolitan Area (Argentina) were retrospectively studied through an amplicon-deep sequencing approach and phylogenetic analyses to characterize hEVs spread. We identified 17 different hEVs types belonging to A, B, and C species. To the best of our knowledge, this is the first report in Buenos Aires for 7 identified hEV-C types. Phylogenetic analyses suggest several introductions of coxsackievirus B4, echovirus 1, and echovirus 9 in the country, along with the national spread reached by some variants. Besides, well-supported monophyletic groups of Argentine, Uruguayan, and Brazilian strains unveiled regional circulation patterns for some variants. These results extend our knowledge about hEVs circulation in Buenos Aires and might exhort authorities to implement more active sewage surveillance in the region.

Expression analysis of selected miR-206 targets from the transforming growth factor-ß signaling pathway in breast cancer.

Breast cancer as a molecularly heterogeneous malignancy is associated with dysregulation of several signaling pathways, including transforming growth factor-ß (TGF-ß) signaling. On the other hand, several recent studies have demonstrated the role of microRNAs (miRNAs) in breast cancer pathogenesis. In the current study, we performed a computerized search to find miR-206 target genes that are functionally linked to the TGF-ß signaling pathway. We selected LEF1, Smad2, and Snail2 genes to assess their expression in 65 breast cancer samples and their adjacent noncancerous tissues (ANCTs) in correlation with expression levels of miR-206 as well as clinicopathological characteristics of patients. miR-206 was significantly downregulated in (Estrogen receptor) ER-positive breast cancer samples compared with their corresponding ANCTs. Association analysis between expression levels of genes and demographic features of patients showed significant association between expressions of SMAD2 and LEF1 genes and body mass index ( P values of 0.03 and 0.02, respectively). miR-206 low-expression levels were associated with TNM stage, mitotic rate, and lymph node involvement ( P values of 0.02, 0.01, and 0.01 respectively). In addition, SMAD2 high-expression levels were associated with HER2 status ( P = 0.02). Consequently, our data highlight the role of TGF-ß signaling dysregulation in the pathogenesis of breast cancer and warrant further evaluation of miRNAs and messenger RNA coding genes in this pathway to facilitate detection of cancer biomarkers and therapeutic targets.

Efficiency of mesenchymal stem cells in treatment of urinary incontinence: a systematic review on animal models.

AIM: In recent years, the administration of stem cells has been considered a new option for treatment of urinary incontinence (UI). In the present study, the efficiency of mesenchymal stem cell (MSC) transplantation in the treatment of UI was evaluated. METHODS: Combinations of the key words 'mesenchymal stem cells', 'MSCs', 'urinary incontinence', 'urethral sphincter' and 'involuntary urination' were searched in PubMed and Science Direct databases. Following application of exclusion criteria to the 1946 papers obtained and review and duplicate articles were removed, 23 articles were considered further. The search was limited to the animal model studies. RESULTS: The data obtained from the evaluation of different studies indicated that the injected MSCs play an important role in the neovascularization and the recovery of muscle cells in UI models through the paracrine process. CONCLUSION: The obtained data suggested that further trials are needed to be focused on clinical phase of MSC therapy on the patients affected by UI.

The Relationship Between the MTHFR C677T Genotypes to Serum Anti-Müllerian Hormone Concentrations and In Vitro Fertilization/Intracytoplasmic Sperm Injection Outcome.

BACKGROUND: The expression of the 5,10-methylentetrahydrofolate reductase (MTHFR) gene in human oocytes and preimplantation embryos suggests that the MTHFR gene is involved in folliculogenesis and female reproduction. Considering the importance of the MTHFR gene on female reproduction, the aim of this study was to evalu- ate the influence of MTHFR C677T polymorphism on ovarian marker reserve, particularly serum anti-Müllerian hormone (AMH) levels, and ovarian response as well as clinical pregnancy rates after in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI). METHODS: A total of 137 women who underwent ART treatment due to male factor infertility enrolled in this study. Genotyping of MTHFR C677T polymorphism and serum AMH concentrations were performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and an ultrasensitive enzymelinked immunosorbent assay (ELISA). RESULTS: Women with the TT genotype showed significantly higher AMH levels (4.5 ± 3.2 ng/mL) compared to carriers of other genotypes after ovarian stimulation. We observed a nonsignificant trend towards lower clinical pregnancy rates in patients with the TT (23.1%) versus CT (48.4%) genotypes (p = 0.2). No significant differences existed in terms of miscarriage and live birth rates among the groups. Multivariable logistic regression revealed that the duration of infertility and AFC were important predictive variables for the live birth rate. CONCLUSIONS: Our results confirmed that the presence of the T mutant allele of the 677 polymorphism in the MTHFR gene led to an increased trend in AMH levels. Interestingly, we observed that the numbers of oocytes retrieved decreased in the mutated genotypes. We have not observed this trend in relation to oocyte maturity. The influence of the MTHFR C677T polymorphism on embryo quality and pregnancy rate after ART cycles remains unclear.

Application of Blood-Brain Barrier Permeability Imaging in Global Cerebral Edema.

BACKGROUND AND PURPOSE: Blood-brain barrier permeability is not routinely evaluated in the clinical setting. Global cerebral edema occurs after SAH and is associated with BBB disruption. Detection of global cerebral edema using current imaging techniques is challenging. Our purpose was to apply blood-brain barrier permeability imaging in patients with global cerebral edema by using extended CT perfusion. MATERIALS AND METHODS: Patients with SAH underwent CTP in the early phase after aneurysmal rupture (days 0-3) and were classified as having global cerebral edema or nonglobal cerebral edema using established noncontrast CT criteria. CTP data were postprocessed into blood-brain barrier permeability quantitative maps of PS (permeability surface-area product), K(trans) (volume transfer constant from blood plasma to extravascular extracellular space), Kep (washout rate constant of the contrast agent from extravascular extracellular space to intravascular space), VE (extravascular extracellular space volume per unit of tissue volume), VP (plasmatic volume per unit of tissue volume), and F (plasma flow) by using Olea Sphere software. Mean values were compared using t tests. RESULTS: Twenty-two patients were included in the analysis. Kep (1.32 versus 1.52, P < .0001), K(trans) (0.15 versus 0.19, P < .0001), VP (0.51 versus 0.57, P = .0007), and F (1176 versus 1329, P = .0001) were decreased in global cerebral edema compared with nonglobal cerebral edema while VE (0.81 versus 0.39, P < .0001) was increased. CONCLUSIONS: Extended CTP was used to evaluate blood-brain barrier permeability in patients with SAH with and without global cerebral edema. Kep is an important indicator of altered blood-brain barrier permeability in patients with decreased blood flow, as Kep is flow-independent. Further study of blood-brain barrier permeability is needed to improve diagnosis and monitoring of global cerebral edema.

Evaluating CT Perfusion Deficits in Global Cerebral Edema after Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Global cerebral edema is an independent predictor of mortality and poor outcomes after aneurysmal SAH. Global cerebral edema, a complex disease process, is thought to be associated with an altered cerebral autoregulatory response. We studied the association between cerebral hemodynamics and early global cerebral edema by using CTP. MATERIALS AND METHODS: We retrospectively studied consecutive patients with aneurysmal SAH with admission CTP performed at days 0-3. Two neuroradiologists classified global cerebral edema and hydrocephalus on NCCT performed concurrently with CTP. Global cerebral edema was defined as diffuse effacement of the sulci and/or basal cisterns or diffuse disruption of the cerebral gray-white matter junction. CTP was postprocessed into CBF and MTT maps by using a standardized method. Quantitative analysis of CTP was performed by using standard protocol with ROI sampling of the cerebral cortex. The Fisher exact test, Mann-Whitney test, and independent-samples t test were used to determine statistical associations. RESULTS: Of the 45 patients included, 42% (19/45) had global cerebral edema and 58% (26/45) did not. Patient groups with and without global cerebral edema were well-matched for demographic and clinical data. Patients with global cerebral edema were more likely to have qualitative global CTP deficits than those without global cerebral edema (P = .001) with an OR = 13.3 (95% CI, 2.09-138.63). Patients with global cerebral edema also had a very strong trend toward statistical significance, with reduced quantitative CBF compared with patients without global cerebral edema (P = .064). CONCLUSIONS: Global perfusion deficits are significantly associated with global cerebral edema in the early phase after aneurysmal SAH, supporting the theory that hemodynamic disturbances occur in global cerebral edema.

Evaluating blood-brain barrier permeability in delayed cerebral infarction after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Patients with SAH are at increased risk of delayed infarction. Early detection and treatment of delayed infarction remain challenging. We assessed blood-brain barrier permeability, measured as permeability surface area product, by using CTP in patients with SAH with delayed infarction. MATERIALS AND METHODS: We performed a retrospective study of patients with SAH with delayed infarction on follow-up NCCT. CTP was performed before the development of delayed infarction. CTP data were postprocessed into permeability surface area product, CBF, and MTT maps. Coregistration was performed to align the infarcted region on the follow-up NCCT with the corresponding location on the CTP maps obtained before infarction. Permeability surface area product, CBF, and MTT values were then obtained in the location of the subsequent infarction. The contralateral noninfarcted region was compared with the affected side in each patient. Wilcoxon signed rank tests were performed to determine statistical significance. Clinical data were collected at the time of CTP and at the time of follow-up NCCT. RESULTS: Twenty-one patients with SAH were included in the study. There was a statistically significant increase in permeability surface area product in the regions of subsequent infarction compared with the contralateral control regions (P < .0001). However, CBF and MTT values were not significantly different in these 2 regions. Subsequent follow-up NCCT demonstrated new delayed infarction in all 21 patients, at which time 38% of patients had new focal neurologic deficits. CONCLUSIONS: Our study reveals a statistically significant increase in permeability surface area product preceding delayed infarction in patients with SAH. Further investigation of early permeability changes in SAH may provide new insights into the prediction of delayed infarction.

Cost-effectiveness of CT angiography and perfusion imaging for delayed cerebral ischemia and vasospasm in aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia and vasospasm are significant complications following SAH leading to cerebral infarction, functional disability, and death. In recent years, CTA and CTP have been used to increase the detection of delayed cerebral ischemia and vasospasm. Our aim was to perform comparative-effectiveness and cost-effectiveness analyses evaluating CTA and CTP for delayed cerebral ischemia and vasospasm in aneurysmal SAH from a health care payer perspective. MATERIALS AND METHODS: We developed a decision model comparing CTA and CTP with transcranial Doppler sonography for detection of vasospasm and delayed cerebral ischemia in SAH. The clinical pathways were based on the "Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage: A Guideline for Healthcare Professionals from the American Heart Association/American Stroke Association" (2012). Outcome health states represented mortality and morbidity according to functional outcomes. Input probabilities of symptoms and serial test results from CTA and CTP, transcranial Doppler ultrasound, and digital subtraction angiography were directly derived from an SAH cohort by using a multinomial logistic regression model. Expected benefits, measured as quality-adjusted life years, and costs, measured in 2012 US dollars, were calculated for each imaging strategy. Univariable, multivariable, and probabilistic sensitivity analyses were performed to determine the independent and combined effect of input parameter uncertainty. RESULTS: The transcranial Doppler ultrasound strategy yielded 13.62 quality-adjusted life years at a cost of $154,719. The CTA and CTP strategy generated 13.89 quality-adjusted life years at a cost of $147,097, resulting in a gain of 0.27 quality-adjusted life years and cost savings of $7622 over the transcranial Doppler ultrasound strategy. Univariable and multivariable sensitivity analyses indicated that results were robust to plausible input parameter uncertainty. Probabilistic sensitivity analysis results yielded 96.8% of iterations in the right lower quadrant, representing higher benefits and lower costs. CONCLUSIONS: Our model results suggest that CTA and CTP are the preferred imaging strategy in SAH, compared with transcranial Doppler ultrasound, leading to improved clinical outcomes and lower health care costs.

CT perfusion for detection of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia is a significant cause of morbidity and mortality after aneurysmal SAH, leading to poor outcomes. The purpose of this study was to evaluate the usefulness of CTP in determining delayed cerebral ischemia in patients with aneurysmal SAH. MATERIALS AND METHODS: We conducted a systematic review evaluating studies that assessed CTP in patients with aneurysmal SAH for determining delayed cerebral ischemia. Studies using any of the following definitions of delayed cerebral ischemia were included in the systematic review: 1) new onset of clinical deterioration, 2) cerebral infarction identified on follow-up CT or MR imaging, and 3) functional disability. A random-effects meta-analysis was performed assessing the strength of association between a positive CTP result and delayed cerebral ischemia. RESULTS: The systematic review identified 218 studies that met our screening criteria, of which 6 cohort studies met the inclusion criteria. These studies encompassed a total of 345 patients, with 155 (45%) of 345 patients classified as having delayed cerebral ischemia and 190 (55%) of 345 patients as not having delayed cerebral ischemia. Admission disease severity was comparable across all groups. Four cohort studies reported CTP test characteristics amenable to the meta-analysis. The weighted averages and ranges of the pooled sensitivity and specificity of CTP in the determination of delayed cerebral ischemia were 0.84 (0.7-0.95) and 0.77 (0.66-0.82), respectively. The pooled odds ratio of 23.14 (95% CI, 5.87-91.19) indicates that patients with aneurysmal SAH with positive CTP test results were approximately 23 times more likely to experience delayed cerebral ischemia compared with patients with negative CTP test results. CONCLUSIONS: Perfusion deficits on CTP are a significant finding in determining delayed cerebral ischemia in aneurysmal SAH. This may be helpful in identifying patients with delayed cerebral ischemia before development of infarction and neurologic deficits.

Polymorphisms of the angiotensin converting enzyme gene in Iranian Azeri Turkish women with unexplained recurrent pregnancy loss.

Several factors which influence the balance between fibrinolysis and coagulation pathways play role in the outcome of conception. A large body of studies demonstrate that gene variations are associated with recurrent pregnancy loss (RPL) by different mechanisms. We aimed to determine the allele and genotype frequencies of the angiotensin converting enzyme (ACE) gene in Iranian Azeri Turkish women with unexplained RPL. Fifty patients with RPL and 63 fertile healthy women as controls were entered in the study. A standard method was used for DNA isolation. All genotypes were determined using PCR. Our analysis showed that patient (chi(2) = 0.347, p = 0.84) and control (chi(2) = 0.77, p = 0.68) groups fitted the Hardy-Weinberg equilibrium strongly. No significant differences were found regarding the frequencies of ACE genotypes [deletion/deletion (D/D), insertion/deletion (I/D) and insertion/insertion (I/I)] and alleles between cases and controls. Based on these findings, we could not find any association between ACE (D/D, I/D and I/I) gene polymorphisms and RPL.

Population pharmacokinetics of the humanised monoclonal antibody, HuHMFG1 (AS1402), derived from a phase I study on breast cancer.

BACKGROUND: HuHMFG1 (AS1402) is a humanised monoclonal antibody that has undergone a phase I trial in metastatic breast cancer. The aim of this study was to characterise the pharmacokinetics (PKs) of HuHMFG1 using a population PK model. METHOD: Data were derived from a phase I study of 26 patients receiving HuHMFG1 at doses ranging from 1 to 16 mg kg(-1). Data were analysed using NONMEM software and covariates were included. A limited sampling strategy (LSS) was developed using training and a validation data set. RESULTS: A linear two-compartment model was shown to be adequate to describe data. Covariate analysis indicated that weight was not related to clearance. An LSS was successfully developed on the basis of the model, in which one sample is collected immediately before the start of an infusion and the second is taken at the end of infusion. CONCLUSION: A two-compartment population PK model successfully describes HuHMFG1 behaviour. The model suggests using a fixed dose of HuHMFG1, which would simplify dosing. The model could be used to optimise dose level and dosing schedule if more data on the correlation between exposure and efficacy become available from future studies. The derived LSS could optimise further PK assessment of this antibody.

Differential effects of weekly and daily exposure to the hot plate on the rat's behavior.

Animals were assigned to two groups: weekly stimulated (WS, n = 30) and daily stimulated (DS, n = 30). Three hot plate tests (55.0 +/- 0.5 degree C, 45 s exposure time) were carried out for each rat. Behavior was videotaped and analyzed by a 14-pattern ethogram and a software package. A cluster analysis revealed that naive rats mainly displayed: i) exploratory patterns (walk-sniff, immobile-sniff), ii) primary noxious-evoked elements (forepaw licking, hindpaw licking, stamping), iii) escape responses (learning posture, jumping), and iv) hindleg withdrawal, an independent noxious-evoked element. The main behavioral changes over time were: i) exploratory behavior was habituated in both groups, ii) sensitization of primary noxious-evoked elements was observed only in the WS group, iii) escape elements were enhanced in both groups, although to less extent in the DS group, and iv) hindleg withdrawal was enhanced in both groups. Furthermore, in the WS group, the nociceptive threshold was significantly decreased, and cluster analysis indicated reliable changes over time. Results suggest that a sensitization phenomenon came about when rats were tested weekly, but was minimized by using the daily testing schedule. This study indicated that an ethological analysis is useful to categorize the rat's patterns in the hot plate test, as well as to follow the gradual changes in responses when repeated measures are used.

Effects of morphine and naloxone on behaviour in the hot plate test: an ethopharmacological study in the rat.

The objectives of this study were: i) to analyse the effects of morphine and naloxone on the rat's behaviour in the hot plate test using an ethological approach, and ii) to compare the effectiveness of repeated versus single test paradigms. Animals received either morphine (0, 3, 6 or 9 mg/kg SC) or naloxone (0, 0.01, 0.1 or 1 mg/kg SC). For repeated hot plate measures, rats were tested before and 60, 120, 180 and 240 min following morphine treatment, as well as 30, 60, 90 and 120 min after naloxone injection. For the single test schedule, rats were tested only once 60 min after morphine or 30 min after naloxone administration, or at 60, 120, 180, 240 and 300 min after 9 mg/kg morphine treatment. Behaviour was videotaped and analysed by an ethogram and ethological techniques. A cluster analysis revealed that the most frequently displayed patterns could be categorised into exploratory sniffing reactions (walk-sniff, immobile-sniff) and noxious-evoked elements, including primary (paw-licking, stamping), escape (jumping, leaning posture) and independent (hindleg-withdrawal) patterns. During repeated tests, morphine treatment induced: i) a maximum hypoalgesic effect 60 min post-injection (noxious-evoked patterns were significantly reduced), and ii) an unexpected "thermal hyperreactivity rebound effect" after 120 min (paw-licking and hindleg-withdrawal were enhanced), although changes in hindpaw-licking are more indicative of a hyperalgesic rebound effect. Most changes were quite similar during the single test schedule at 60 and 120 min after morphine injection. With regard to naloxone treatment, jumping latency was significantly decreased during the repeated test schedule, but not on single exposure to the plate. Other elements were facilitated, however, in the single test (stamping, leaning posture, hindleg-withdrawal). The results indicated that both repeated and single tests paradigms are of value for testing the effects of morphine and naloxone on rats. However, under our conditions the single test paradigm gave a better picture of the overall effects of the drug. Learning as well as habituation and sensitization may mask certain effects during repeated tests. In conclusion, an ethological analysis of the rat's behaviour in the hot plate test following administration of morphine and naloxone has been validated in this study.

Structure of the rat's behaviour in the hot plate test.

The objectives of the study were: (i) to elaborate an ethogram of the rat's behaviour during the hot plate test, (ii) to analyse the rat's responses to the nociceptive heat stimulus by using ethological techniques, and (iii) to discern the suitable pattern or patterns to evaluate the rat's reaction to the noxious stimulus. Male Wistar rats (n = 30) were employed, and one hot plate test was carried out for each rat. The platform (Socrel DS37) was maintained at 55.0 +/- 0.5 degrees C, and the exposure time was 45 s. Behaviour was videotaped and analysed by an ethogram and a software package. Every pattern parameter (frequency, duration and latency for the first occurrence) was quantified. Cluster and Markovian analyses were also employed, whereby a dendrogram and a Markov chain were obtained, respectively. The ethogram was composed of twelve patterns: immobile-sniff, walk-sniff, rearing, forepaw-licking, hindpaw-licking, face-washing, body-cleaning, stamping, hindleg-withdrawal, leaning posture, jumping off, and freezing. Cluster analysis indicated that the most frequent patterns could be classified into three categories: sniffing responses (immobile-sniff, walk-sniff), primary noxious-evoked patterns (forepaw-licking, hindpaw-licking, stamping), and escape noxious-evoked responses (leaning posture, jumping off). Hindleg-withdrawal would be an independent noxious-evoked pattern, and freezing an alerting behaviour. The ethological information could be useful to better elucidate effects on rats' behaviour of drug treatment or other phenomena during the hot plate test.

Accumbens lesion in female rats increases mount rejection without modifying lordosis.

Ovariectomized Wistar rats received bilateral electrolytic (n = 24) or sham (n = 11) lesion of the nucleus accumbens. Following priming with estradiol benzoate (25 micrograms/rat) and progesterone (0.5 mg/rat) they were tested for sexual behavior with a stud male. Tests were carried out once prior to operation and twice postoperatively. Both lordosis and rejection behaviors as responses to male mount attempts were evaluated for each session. Proceptive patterns (hopping, darting and presenting) were also recorded. Females with accumbens lesion did not differ from control animals either with regard to lordosis or to soliciting behaviors. On the contrary, the lesioned group showed a statistically significant increase in rejection behavior in both postoperative sessions (p less than 0.05 and p less than 0.002). In conclusion, nucleus accumbens lesion dissociated the normal correlation between lordosis and rejection responses to male mount attempts without affecting soliciting behaviors. This finding is thought to be related to the hyperreactivity produced by nucleus accumbens lesion.

Effects of nucleus accumbens lesion on female rat sexual receptivity and proceptivity in a partner preference paradigm.

A partner preference paradigm, stud male vs estrous female, was used to study sexual behavior. Ovariectomized Wistar rats received bilateral electrolytic (n = 33) or sham (n = 16) lesion of the nucleus accumbens. Animals were tested in two different experimental situations, either with stimulus animals tethered (test with possibility of mating) or with stimulus animals behind a wire mesh (test without possibility of mating). Each test was carried out once prior to surgery and twice postoperatively following priming with estradiol benzoate and progesterone. Lordosis, rejection behaviors and soliciting patterns were scored in tests with tethered stimulus animals. The tendency of the experimental female to approach and remain in the vicinity of each stimulus animal was quantified to study the partner preference. Nucleus accumbens lesion increased the number of rejection responses to male mount attempts without modifying either receptivity estimated by lordosis reflex or soliciting behaviors. Control females showed a statistically significant preference for the male throughout the experiments. Lesioned females exhibit a preference for the male only in the test without sexual interaction possibility. This preference disappeared in the test with possibility of mating and it was even reversed when the male showed copulatory activity. These results, together with the absence of changes in lordosis behavior and soliciting activity, suggest that both the inversion in preference and the higher levels of mount rejections found in the lesioned animals are more likely attributable to hyperreactivity to the copulatory stimulus rather than an alteration in the female's rat sexual motivation.

Behavioral study in rats of paired accumbens-lesioned residents and intact intruders.

Behavior in accumbens-lesioned male Wistar rats during paired encounters was assessed by several parameters, scores and cluster analysis based on similarity between patterns. Encounters were videotaped and analyzed by an ethogram and a software package previously elaborated. Residents were lesioned (n = 23) or sham operated (n = 10). A reactivity score was used to corroborate the effectiveness of the lesions. Although accumbens lesions produced the well-known increase in reactivity and enhancement of piloerection, only subtle changes were elucidated by the ethological analysis. Dendrograms revealed postoperative changes in the lesioned rats as well as in the intruders paired with them. Threat category in the lesion group dissociated in threat with arched-back attitude and threat with erect posture. In intruders paired with lesioned rats, compared with those paired with sham-operated animals, the patterns of freezing and on-back became mainly associated with immobile-crouch instead of upright defense posture, and the category of defense/submission was not observed in dendrograms.

Effects of nucleus accumbens lesions in rats on spatial preference in an open field.

Selective lesions placed in three different regions of the nucleus accumbens were performed to assess their effects on spatial preference in the rat. Histological verification allowed to establish three groups of lesioned animals: medial, intermediate and lateral. Sham operations involved all procedures except the passing of a current. All animals were tested once prior to operation and twice postoperatively. Sherman's directionality score (DS) was adopted. Positive values indicate right side preference and negative ones leftward bias. Statistical analysis revealed that rats used in this study showed a nonsignificant spontaneous right side preference in the open field (DS = +0.08). Medial and intermediate lesions increased the right side bias (DS = +0.37), whereas lateral lesioned animals reversed their preoperative rightward bias and showed a significant left side preference (DS = -0.48). These results suggest a participation of the nucleus accumbens in spatial preference and are considered to be due to the well known uneven distribution of the afferent and efferent fiber systems within the nucleus.