Emotional Value of Fear Memory and the Role of the Ventral Hippocampus in Systems Consolidation.

Recent studies have explored the circuitry involving the ventral hippocampus (vHPC), the amygdala, and the prefrontal cortex, a pathway mainly activated to store contextual information efficiently. Lesions in the vHPC impair remote memory, but not in the short term. However, how the vHPC is affected by distinct memory strength or its role in systems consolidation has not yet been elucidated. Here, we investigated how distinct training intensities, with strong or weak contextual fear conditioning, affect activation of the dorsal hippocampus (dHPC) and the vHPC. We found that the time course of memory consolidation differs in fear memories of different training intensities in both the dHPC and vHPC. Our results also indicate that memory generalization happens alongside greater activation of the vHPC, and these processes occur faster with stronger fear memories. The vHPC is required for the expression of remote fear memory and may control contextual fear generalization, a view corroborated by the fact that inactivation of the vHPC suppresses generalized fear expression, making memory more precise again. Systems consolidation occurs concomitantly with greater activation of the vHPC, which is accelerated in stronger fear memories. These findings lead us to propose that greater activation of the vHPC could be used as a marker for memory generalization.

Structural and functional properties of the Kunitz-type and C-terminal domains of Amblyomin-X supporting its antitumor activity.

Amblyomin-X is a Kunitz-type FXa inhibitor identified through the transcriptome analysis of the salivary gland from Amblyomma sculptum tick. This protein consists of two domains of equivalent size, triggers apoptosis in different tumor cell lines, and promotes regression of tumor growth, and reduction of metastasis. To study the structural properties and functional roles of the N-terminal (N-ter) and C-terminal (C-ter) domains of Amblyomin-X, we synthesized them by solid-phase peptide synthesis, solved the X-Ray crystallographic structure of the N-ter domain, confirming its Kunitz-type signature, and studied their biological properties. We show here that the C-ter domain is responsible for the uptake of Amblyomin-X by tumor cells and highlight the ability of this domain to deliver intracellular cargo by the strong enhancement of the intracellular detection of molecules with low cellular-uptake efficiency (p15) after their coupling with the C-ter domain. In contrast, the N-ter Kunitz domain of Amblyomin-X is not capable of crossing through the cell membrane but is associated with tumor cell cytotoxicity when it is microinjected into the cells or fused to TAT cell-penetrating peptide. Additionally, we identify the minimum length C-terminal domain named F2C able to enter in the SK-MEL-28 cells and induces dynein chains gene expression modulation, a molecular motor that plays a role in the uptake and intracellular trafficking of Amblyomin-X.

Liver transplantation for hilar inflammatory myofibroblastic tumor: Case report and review of the literature.

BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) of the liver are rare neoplasms. These tumors are difficult to distinguish from other neoplasms by radiological examination, have uncertain evolution, and there is no consensus on the treatment of these lesions. Hilar tumors can involve the portal vein, hepatic artery, bile duct, and spread to the branches of the portal triad, causing obstructive symptoms, occlusive phlebitis, and portal hypertension. Thus, liver transplantation (LT) is an excellent alternative for locally advanced hilar tumors, since it ensures complete tumor resection with free margins. METHODS/RESULTS: We present a literature review and a case report showing a 3-year-old boy with liver IMT invading the hepatic hilum and inferior vena cava, who underwent a successful living donor liver transplantation that required portal vein and vena cava replacement. CONCLUSION: The incidence of hilar IMTs is low and there is no well-established standard treatment. Liver transplantation for a hilar tumor with vascular invasion was acceptable in this case because the radically of the surgery was the key for the cure, and because the tumor was benign in nature.

A comparison of the physical demands associated with various right-angle direct-current power tools.

This work examined the physical demands associated with 4 commercially available direct current right-angle power tools along with their computer controlled fastening strategies. Physical demands were measured via an external instrumented handle that could also control the trigger of each tool. Data revealed that forces recorded by the external handle for each of the 4 tools differed. Independent of Joint-Hardness and Target Torque the Atlas Copco TurboTight® and Cleco Low Torque Reaction fastening strategies, both using a rapid spindle-head rotation strategy, produced the lowest peak and impulse force, respectfully, when compared to the 2 tools that were designed to fasten with a longer duration. This work has shown that short duration fastening strategies provide an ergonomics benefit to the users as it requires less force to operate, such force reduction in previous research has been linked to reduced handle displacement and lower muscle effort.

Physical demands associated with right-angle direct-current power-tools: An evaluation of current technology.

The purpose of this work was to evaluate the physical demands associated with three direct current powered right-angle power tool tightening strategies at various fastener-location-orientations, target torques and joint-hardness. Physical demands were measured using surface electromyography, handle force and upper body kinematics. Results identified TurboTight®, a rapid and short duration fastening strategy, to produce lower handle force impulse, less joint angle displacement, and lower EMG magnitudes when compared to the longer duration fastening strategies tested. The reduced magnitudes associated with TurboTight®, independent of fastener-location-orientations, target torques and joint-hardness, indicate a lower physical demand on power tool operators, providing a significant ergonomic benefit when compared to the slower fastening strategies.

Increased grp78 transcription is correlated to reduced tlr4 transcription in patients surviving sepsis.

Regulated transcriptional readthrough during stress maintains genome structure and ensures access to genes that are necessary for cellular recovery. A broad number of genes, including of the bacterial sensor Toll-like receptor 4 (TLR-4), are markedly transcribed on initiating the systemic inflammatory response. Here we study the transcriptional patterns of tlr4 and of its modulator grp78 during human sepsis, and establish their correlations with the outcome of patients. We measured the daily tlr4 and grp78 RNA expression levels in peripheral blood of septic patients, immediately after admission to intensive care, and modeled these RNA values with a sine damping function. We obtained negative correlations between the transcription of tlr4 and grp78 RNA in the survivor group. In contrast, such relation is lost in the deceased patients. Loss of transcriptional homeostasis predicted by our model within the initial 4 days of hospitalization was confirmed by death of those patients up to 28 days later.

Silver/polysaccharide-based nanofibrous materials synthesized from green chemistry approach.

In this contribution a novel green chemistry approach for the synthesis of nanofibrous materials based on blends of carboxymethyl-cellulose (CMC)-silver nanoparticles (AgNPs) composite and polyvinyl-alcohol (PVA) is proposed. These nanofibrous materials were obtained from the electrospinning of blends of aqueous solutions of CMC-AgNPs composite and PVA, which were prepared at different CMC/PVA weight ratios in order to electrospin nanofibers applying a constant tension of 15kV. The synthesized materials were characterized by means of transmission electron microscopy, scanning electron microscopy; as well as Fourier-transform infrared, ultraviolet and Raman spectroscopic techniques. Experimental evidence suggests that the diameter of the nanofibers is thinner than any other reported in the literature regarding the electrospinning of CMC. This feature is related to the interactions of AgNPs with carboxyl functional groups of the CMC, which diminish those between the later and acetyl groups of PVA.

Immunosuppressive PAS-1 is an excretory/secretory protein released by larval and adult worms of the ascarid nematode Ascaris suum.

Helminths use several strategies to evade and/or modify the host immune response, including suppression or inactivation of the host antigen-specific response. Several helminth immunomodulatory molecules have been identified. Our studies have focused on immunosuppression induced by the roundworm Ascaris suum and an A. suum-derived protein named protein 1 from A. suum (PAS-1). Here we assessed whether PAS-1 is an excretory/secretory (E/S) protein and whether it can suppress lipopolysaccharide-induced inflammation. Larvae from infective eggs were cultured in unsupplemented Dulbecco's modified Eagle medium (DMEM) for 2 weeks. PAS-1 was then measured in the culture supernatants and in adult A. suum body fluid at different time points by enzyme-linked immunosorbent assay (ELISA) with the monoclonal antibody MAIP-1. Secreted PAS-1 was detected in both larval culture supernatant and adult body fluid. It suppressed lipopolysaccharide (LPS)-induced leucocyte migration and pro-inflammatory cytokine production, and stimulated interleukin (IL)-10 secretion, indicating that larval and adult secreted PAS-1 suppresses inflammation in this model. Moreover, the anti-inflammatory activity of PAS-1 was abolished by treatment with MAIP-1, a PAS-1-specific monoclonal antibody, confirming the crucial role of PAS-1 in suppressing LPS-induced inflammation. These findings demonstrate that PAS-1 is an E/S protein with anti-inflammatory properties likely to be attributable to IL-10 production.

[Premature ejaculation]. / L'éjaculation prématurée.

INTRODUCTION: Premature ejaculation (PE) is the most common masculine sexual disorder with a potentially deleterious effect on the patient's morale and the relationship with the partner. It is underdiagnosed, or self-diagnosed, and as patients hesitate to confide in their doctor, and doctors do not enquire about it, it is rarely treated. Effective medication does exist, in particular serotonin reuptake inhibitors. METHODS: Medical literature was reviewed and combined with expert opinion of the authors. RESULTS: The distinction is rarely made between lifelong, primary and acquired PE but this distinction determines the choice and efficacy of the therapeutic strategy. Originally seen from a psychoanalytical viewpoint, it was later seen from a behavioral angle. For primary PE, according to Kaplan and contemporary sexology, a psycho-sexological concept has been evoked: sinful stain and symbolic frustration of the woman following an unresolved conflict, revived by a conflict with the partner. For primary PE, a pathophysiological origin with the notion of genetic susceptibility with possible variation of the central serotoninergic neurotransmission has been suggested. We give here the different etiological hypotheses, the clinical types and the different therapeutic strategies for management of PE (a more precise etio-pathological diagnosis). Some key points are highlighted: factors related to the partner are underestimated, her 'use' as therapy is underexploited, an integrated or combined approach which is potentially more efficacious can go beyond the prolongation of the ejaculation time lapse to optimize the patient's relationship and equilibrium. Maintaining the results over time is however problematic. CONCLUSION: When rapid ejaculation causes a distress, it is a sexual dysfunction deserving medical and/or psycho-sexological management currently evidence-based.

Bacterial toxins: an overview on bacterial proteases and their action as virulence factors.

Bacterial pathogenicity is a result of a combination of factors, including resistance to environmental threats and to the host's defenses, growth capability, localization in the host, tissue specificity, resource obtaining mechanisms and the bacterium's own defenses to aggression. A variety of bacterial components, often specific to each strain, are involved in the microorganism's survival, adhesion and growth in the host. Many of them are harmful and, therefore, are called virulence factors. The effects caused by the virulence factors determine the degree of aggressivity of the strain. In many cases the virulence factors are secreted proteins or enzymes, sometimes performing very specific functions. The enzymatic activity is directed to specific proteins from cell membranes, synaptic vesicle fusion proteins, among other important targets. One of the most toxic bacterial proteins is secreted by Clostridium botulinum, targeted to synaptic vesicle fusion proteins, cleaving them with a zinc-metalloprotease activity, which results in severe neurotoxic effects with a lethal dose as low as eight nanograms per kilogram of body weight. The tetanus neurotoxin acts in a similar way but is less active and Bacillus anthracis also presents a potent metalloprotease activity. In this work we describe a selection of these specially interesting and important bacterial proteins and proteases, stressing their relevance in the pathological process and in medical studies.

[Severe child abuse admitted to paediatric ICU]. / Maltrato infantil grave en la unidad de cuidados intensivos pediátricos.

OBJECTIVE: To describe cases of severe child abuse admitted to PICU. METHODS AND PATIENTS: It is a retrospective study (2000-2008) in which patients diagnosed with physical child abuse admitted to PICU were included. Other abuse patterns were excluded (severe negligence, sexual abuse or scalding). RESULTS: There were 8 patients included (3 boys and 5 girls). The median age was 5.2 months, with 6 patients were less than 7 months old. The most frequent sign was neurological symptoms: seizures (4 patients), subdural haematoma (2 patients), traumatic brain injury (1 patient). Other: haemothorax (1 patient) and cardiac arrest of no known aetiology (1 patient). The CT showed a subdural haematoma in 5 patients, 3 of which needed surgical drainage. Child abuse was confirmed using the social history and the presence of inflicted injuries. There were long bones fractures (tibia, ulna and radius, bilateral rib fractures) in 3 patients and 4 patients had retinal haemorrhages. There was one death and 3 had severe neurological after effects. CONCLUSION: Severely abused children can be falsely diagnosed with a casual neurological disease. The most frequent injury is subdural haematoma with or without another injury associated to child abuse. It very important to diagnose child abuse in order to prevent recurrent injuries.

Granular Vulvovaginitis Syndrome in Nelore pubertal and post pubertal replacement heifers under tropical conditions: role of Mycoplasma spp., Ureaplasma diversum and BHV-1.

In order to determine the role of Mycoplasma spp, Ureaplasma diversum and BHV-1 as causal agents of Granular Vulvovaginitis Syndrome in Nelore heifers raised under tropical conditions and based on the hypothesis that stressful conditions during puberty or breeding season would be a determinant factor for the infection, 340 heifers not vaccinated against BHV-1 were divided in Post-pubertal, in the beginning of the first breeding season, and Pubertal heifers. The vaginal lesion score (VLS) Grade 1 to 4 was giving according to lesion area and severity. Vaginal mucus was used to isolate Mycoplasma spp., Ureaplasma diversum and BHV-1. The predominant VLS was 2. No sample was positive for BHV-1; 48% were positive for Mycoplasma spp., Ureaplasma diversum, or both, with predominance of Ureaplasma diversum. Serum neutralization for BHV-1 showed more positive animals in pubertal group (23%); 3 of the paired sera demonstrated seroconversion. These data indicated that post-pubertal and pubertal Nelore heifers raised under extensive conditions are more susceptible to Mycoplasma spp. and Ureaplasma diversum. The hypothesis that the stress of pubertal period could lead to an acute vaginal infection by HBV-1 was not proofed.

Nitric oxide synthase activity and endogenous inhibitors in rats recovered from allergic encephalomyelitis.

We have previously reported that in comparison with normal rats, the presence of experimental allergic encephalomyelitis (EAE) leads to decreased endogenous inhibitory activity (EIA) of Ca2+-dependent nitric oxide synthase (NOS) in both brain and serum, and increased expression of protein 3-nitrotyrosine (NT) in brain. In this work we show that animals recovered from the clinical signs of EAE are not different from controls in terms of either brain NOS activity, EIA of NOS, or NT expression. These results suggest that parallel to the reversal of the disease symptoms, a normalization of the production of nitric oxide and related species occurs.

Nitric oxide synthase activity and endogenous inhibitors in rats recovered from allergic encephalomyelitis

We have previously reported that in comparison with normal rats, the presence of experimental allergic encephalomyelitis (EAE) leads to decreased endogenous inhibitory activity (EIA) of Ca2+-dependent nitric oxide synthase (NOS) in both brain and serum, and increased expression of protein 3-nitrotyrosine (NT) in brain. In this work we show that animals recovered from the clinical signs of EAE are not different from controls in terms of either brain NOS activity, EIA of NOS, or NT expression. These results suggest that parallel to the reversal of the disease symptoms, a normalization of the production of nitric oxide and related species occurs.

The effect of long-term treatment with erdosteine on chronic obstructive pulmonary disease: the EQUALIFE Study.

Erdosteine is a new thiol compound with effects on bacterial adhesiveness as well as antioxidant and mucoactive properties. The EQUALIFE study, a fully randomized, double-blind, placebo-controlled, parallel-group, multicenter study, was designed to assets the effectiveness of long-term treatment with erdosteine in patients with moderate chronic obstructive pulmonary disease (COPD). One hundred and fifty-five patients received oral erdosteine, 300 mg b.i.d., or placebo for 8 months during the winter season to assess the effect of treatments on exacerbation rate, hospitalization, lung function and quality of life, assessed using the Short Form 36 and the St. George's Respiratory Questionnaire. A pharmacoeconomic analysis was also conducted to compare the two treatments. One hundred and twenty-four patients completed the study with erdosteine (n = 63) or placebo (n = 61). The group of COPD patients who received 8 months of continuous treatment with erdosteine had significantly fewer exacerbations and spent fewer days in the hospital than did the placebo group; furthermore, they had no loss of lung function. Patients in the erdosteine group also showed a significant improvement in health-related quality of life. The mean total COPD-related disease costs per patient were lower in the erdosteine group than in the placebo group over the study period. The results indicate that 8 months of treatment with erdosteine is effective in reducing exacerbation and hospitalization rates and in improving health status. The study suggests that erdosteine is likely to provide an important contribution to the therapy of patients with symptomatic COPD.

Safety, feasibility, and diagnostic accuracy of accelerated high-dose dipyridamole stress echocardiography.

Protocols for dipyridamole stress testing have evolved in the last 16 years in the neverending quest of optimal diagnostic accuracy and user friendliness. Higher dipyridamole dose in a shorter infusion time provides higher sensitivity, but concern over safety is still controversial. An accelerated high-dose (0.84 mg/kg in 6 minutes without atropine) dipyridamole stress test was performed on 1,295 patients in 2 echocardiographic laborotories: Institute of Clinical Physiology of Pisa and Niguarda Hospital of Milan. During testing, there were no deaths and no patients had ventricular fibrillation. Major adverse reactions occurred in 3 cases (1 every 431 studies): 1 myocardial infarction, 1 brief cardiac asystole, and 1 transient ischemic attack. Overall feasibility was 97%. In 66 patients with normal function at rest who were evaluated off therapy, with coronary angiography performed independently of test results, the accelerated high-dose protocol showed a sensitivity of 85% (confidence interval [CI] 73% to 92%) and a specificity of 93% (CI 83% to 97%) for angiographically assessed coronary artery disease (quantitatively assessed diameter reduction > or = 50%). Diagnostic accuracy of the accelerated high dose was 89% (CI 79% to 95%). Thus, accelerated high-dose dipyridamole stress echocardiography was reasonably safe and well tolerated. This protocol is especially appealing for its excellent diagnostic accuracy coupled with the short imaging time and no need for drug cocktails.

Transcription rate modulation through the Trypanosoma cruzi life cycle occurs in parallel with changes in nuclear organisation.

In trypanosomes transcription occurs as large polycistronic units, with trans-splicing and polyadenylation generating each individual mRNA. There are no defined RNA polymerase II promoters and mRNA stabilisation is most likely the process controlling levels of differentially expressed mRNAs, since no selective modulation of gene activity has even been reported at the transcriptional level. Here, we show a large decrease in the transcription rates by RNA polymerases I and II when proliferative forms of Trypanosoma cruzi (epimastigotes and amastigotes) transform into non-proliferative and infective forms (trypomastigotes). We also show that these changes in transcription occur in parallel with modifications in the nuclear structure. While nuclei of proliferative forms are round, contain small amounts of peripheral heterochromatin and a large nucleolus, nuclei of trypomastigotes are elongated, the nucleolus disappears and the heterochromatin occupies most of the nuclear compartment. The decrease in the transcription parallels the nucleolus disassembly, as seen by the dispersion of nucleolar antigens. As T. cruzi cycles continuously through proliferative and infective forms, the molecular mechanisms involved in the control of nuclear organisation and chromatin remodelling can be revealed by this system.

[Relationship between tumor recurrence and the expression of the p53 gene in primary superficial transitional carcinoma of the bladder]. / Relación entre las recidivas tumorales y la expresión del gen p53 en los carcinomas transicionales superficiales primarios de vejiga.

Contribution of 60 patients with primary surface transitional cell tumours of the bladder where nuclear expression of p53 protein was prospectively studied and compared to known prognostic factors in an attempt to find out its role in the development of relapses. An statistically significant relationship was found between the protein expression and cytology, tumoral multifocality, stage, relapse development and tumoral progression. It can be concluded that expression of this protein can be of use as relapse predictor.

The impact of second harmonic imaging on stress echocardiography reading.

BACKGROUND: Noncontrast harmonic significantly improves overall image quality in echocardiography. The aim of this study was to assess whether harmonic imaging, without contrast, impacts on interobserver variability and diagnostic accuracy of "beginners" in stress echocardiography. METHODS: Images at rest and peak stress were obtained in digitized format in 15 consecutive patients (10 males, 5 females, mean age 66 +/- 9 years) and analyzed by 5 inexperienced observers (stress echo beginners) who were blinded to the imaging modality (standard versus harmonic imaging). Each observer graded the image quality as 1 = uninterpretable up to 5 = excellent, in a total of 240 segments. RESULTS: The mean image quality per segment was 2.9 for conventional technology and increased up to 3.6 for harmonic imaging (p < 0.001). The interobserver agreement (> or = 4 out of 5 readers) rose from 46 to 60%. The percentage of uninterpretable segments was 7.5% at rest and 8.9% at peak stress of conventional imaging, and decreased to 4.6 and 6.5%, respectively (p < 0.05) by second harmonic technology. The unanimous reading of two additional independent expert observers was arbitrarily assumed to be the "gold standard" to verify the accuracy of reading of the 5 beginners. The 5 beginners showed poor diagnostic accuracy with fundamental imaging (73%), and they did not improve with second harmonic imaging (70%, NS vs fundamental). CONCLUSIONS: Noncontrast second harmonic imaging improves image quality over conventional imaging. The improved quality of the image deflated interobserver variability but did not determine per se an improvement in the diagnostic accuracy of nonexperienced readers.