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Articles by Marco Pisapia in JoVE

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Long-term Lethal Toxicity Test with the Crustacean Artemia franciscana


JoVE 3790 4/14/2012

1Department of Environmental Quality Monitoring, Institute for Environmental Protection and Research, 2Regional Agency for Environmental Protection in Emilia-Romagna

This study concerns the development and standardization of a valuable methodological protocol to determine long-term (14 days) lethal toxicity exerted by chemical substances, industrial wastewater or sewage and liquid environmental samples on the saltwater crustacean, Artemia franciscana.

Other articles by Marco Pisapia on PubMed

Use of Blood-bank Plasma for the Coagulase Test

[Considerations on Religious Delusion]

[ON THE SUBJECT OF LATE SCHIZOPHRENIA (CLINICAL AND NOSOGRAPHIC CONTRIBUTION)]

MENTAL RETARDATION IN THE SOCIAL WORK CURRICULUM

[LUNG CANCER IN THE FEMALE SEX (BIBLIOGRAPHIC REVISION AND STUDY OF 30 CASES)]

[CLINICO-RADIOLOGIC PICTURE IN ESOPHAGEAL CANCER AND RESULTS OF RADIOTHERAPY]

[Correlation Between Histologic and Scintigraphic Aspects of Malignant Neoformations of the Thyroid]

[Involvement of the Urinary Apparatus in Uterine Neoplasms]

[Considerations on Radiotherapy of Malignant Tumors of the Uterine Body]

[Results of Telecobalt Therapy in Inoperable Malignant Neoplasms of the Rectum and in Recurrences After Surgical Intervention]

[Clinical and Radiological Evolution of Hiatal Hernia with Brachyesophagus in Infancy]

[Cancerization of the Gastric Stump in Patients Subjected to Surgical Operation for Benign Gastroduodenal Ulcer]

[Pulmonary and Skeletal Metastases from Uterine Neoplasms]

[CONSIDERATIONS ON CANCER OF THE CERVIX UTERI TREATED BY RADIOLOGIC THERAPY ALONE]

[Paroxystic Atrial Fibrillation Due to Contusive Craniocerebral Injury]

Wolff-Parkinson-White Syndrome: T Wave Abnormalities During Normal Pathway Conduction

Forty-five patients with Wolff-Parkinson-White syndrome (WPW) were reviewed. The preexcitation using Boineau's classification was: right anterior (six patients), left lateral (nine patients), right posterior (15 patients) and left posterior (15 patients). Normal pathway conduction was observed to occur either spontaneously or after administration of ajmaline, procainamide, or by eye-ball pressure. Disappearance of preexcitation was associated with T wave abnormalities in 39 patients (86.6%). The orientation of the T spatial vector (SAT), after suppression of the WPW aspect, varied according to the site of ventricular preexcitation. In eight patients with left lateral ventricular preexcitation (LLVP), the frontal T wave axis was between +70 degrees and +120 degrees (mean +92 degrees) and the horizontal T wave axis was located in the left anterior quadrant. In the five patients with right anterior ventricular preexcitation (RAVP), the frontal axis was between + 40 degrees and - 10 degrees (mean + 26 degrees) and the horizontal axis was in the left posterior quadrant. The 26 cases with right posterior ventricular preexcitation (RPVP) and left posterior ventricular preexcitation (LPVP) had a frontal axis between - 10 degrees and - 70 degrees (mean -39 degrees) and the horizontal T wave axis in the left anterior quadrant. This study suggests that the T wave anomalies observed after suppression of the WPW aspect are in direct relation to the localization of the preexcitation according to Boineau's classification. The analogy between the abnormalities of the T wave and those which are observed after right ventricular pacing (VP) or after disappearance of left bundle branch block (LBBB) is discussed.

[Sinus Node Disease - Diagnosis and Treatment]

The concept of sinus node disease is defined by a group of clinical and electrocardiographic features related to sinus node dysfunction whatever its mechanism; the organicity of the disease can be proven if total or subtotal histological alterations of the sinus node are demonstrated. The most typical symptoms are neurological (syncopes and dizziness). Sinoatrial block, sinus arrest, sinus bradycardia or bradyarrhythmia, and the bradycardia-tachycardia syndrome are the most usual electrocardiographic aspects. The diagnosis is often rendered difficult by the usually intermittent and frequently nonspecific character of the symptoms and of the ECG signs. Holter monitoring is often essential to resolve these difficulties. If the diagnosis remains dubious, the use of electrophysiological methods is necessary: direct recording of the sinus nodal intracardiac potential can now be added to the classical rapid and premature atrial stimulation, possibly complemented by pharmacological tests. Finally, therapeutic indications can be considered after a correct clinical, electrocardiographical and electrophysiological evaluation of the patient. Medical treatment alone is usually ineffective in controlling the attacks of arrhythmia and the neurological episodes. If the sinus nodal dysfunction is obvious and symptomatic, permanent pacing is the treatment of choice. Its short and medium term results are generally excellent, while the long term results, especially with regard to survival of the patients, could be improved by the most recent pacing techniques.

[Study of Primary and Secondary Sinus Depression After Atrial Stimulation. Use of a Pharmacological Test for Blockade of the Autonomic Nervous System (author's Transl)]

Clinical Use of a New Myocardial Electrode

Prior to clinical use, this new myocardial stimulating electrode was studied in animals in order to test its electrical and mechanical reliability. The Telectronics 030.168 electrode consists of a conductor constructed of 3 stainless steel wires. Its present surface area is 25 mm and its length is 10 mm. The device is easily inserted into the myocardium with a suture and needle and is held in place with a surgical clip. We report observations on 42 patients made over an average follow-up period of 14.6 months. There were no surgical complications and there was no operative mortality. Calculated as an average of recorded electrical measurements, the stimulating threshold was 1.03 volts and 2.40 mA at 500 ms. None of the patients have required further surgery and no malfunctions have been discovered.

Part of the Autonomous Nervous System in the Development of Chaotic Post-extrasystolic Pictures. Electrophysiological and Pharmacological Studies of 49 Cases

The interpretation of post-extrasystolic parameters and their significance is discussed. Programmed extrastimulation according to Strauss was carried out in 49 cases, before and after atropine and propranolol administration. The result was a computable sinoauricular conduction time (SACT), a chaotic picture, or an ascending line without plateau. The patients were selected on basis of their intrinsic heart rates (IHR). If the total SACT exceeded 250 ms, the chaotic post-extrasystolic picture and the ascending 1st phase without plateau were considered pathologic, then after drug testing the ratio of pathologic parameters decreased from 54 to 22% in cases with normal IHR. Including cases with pathologic IHR the ratio increased from 55 to 90%, especially in asynchronous chaotic pictures. After drug testing the chaotic forms were always replaced by a plateau in cases with normal IHR, but in pathologic ones the chaotic picture appeared to be a dominant electrophysiological parameter. It follows that the autonomous nervous system has its part in the development of chaotic post-extrasystolic pictures. A plateau in the post-extrasystolic curve could mean a functional organization and synchronism rather than a conduction disturbance; to the latter a high-level plateau would correspond.

Ocular Manifestations in Thalassemia Minor

The authors report the results of a study on 96 subjects affected with thalassemia minor. The study was made at the Center for the Study of Microcythemia of the OORR in Naples. Of extreme scientific interest is the finding of ocular involvement in 33.3% of the cases. Therefore, after formulating a pathogenetic hypothesis, the authors plan more involved studies and research on these patients.

Synchronized and Desynchronized Sinus Node Activity

In certain cases because of sinus arrhythmia and/or anarchic return and postreturn cycles caused by premature atrial stimulation, the sinoatrial conduction time cannot be calculated since a chaotic postextrasystolic pattern appears. We examined 49 patients with a history and ECG signs suggesting sinus node dysfunction by programmed extrastimulation method as proposed by Strauss et al. prior to and after pharmacologic autonomic blockade (with propranolol 0.2 mg/kg body weight and atropine sulfate 0.04 mg/kg intravenously). Patients with normal intrinsic heart rate (IHR) (n = 31) showed chaotic postextrasystolic responses in 38%, which in every case could be eliminated by autonomic blockade, resulting in a clear I and II phase with a well estimated intrinsic conduction time. Patients with pathologic IHR (n = 18) gave chaotic responses in 22% which after drug testing increased up to 72%. The chaotic postextrasystolic patterns are to be interpreted as the desynchronization of the sinus potentials, while plateau (phase II) as functional integrity, synchronized activity of the sinus node, dependent on the momentaneous balance of the autonomous tone, and on the integrity of the pacemaker cells. The desynchronized chaotic responses are considered on one hand as a dystonic neurovegetative electrophysiologic characteristic, on the other hand as a primary extrastimulation parameter of the intrinsic sinus node dysfunction.

Electrophysiological Effect of Overdrive Suppression and Combined Autonomic Blockade with Propranolol and Atropine in Patients with Sinus Node Dysfunction

Electrophysiological Classification of Normal and Pathological Sinus Node Function

The sympathetic and parasympathetic neurological cardiac effects were blocked with atropine and propranolol. The intrinsic heart rate (IHR) was determined and rapid atrial pacing (RAP) was carried out before and after administration of the drugs. The primary and secondary postpacing parameters were examined in both circumstances. Normal (n = 31) and pathological (n = 20) cases were differentiated on the basis of the IHR. In the secondary phase (PPC 2-10) after autonomic blockade returned to the basic frequency was of exponential character in the great majority of normal IHR cases. Anomalies may appear in both the primary and secondary phases. They are of different types: one of them concerns the recovery time; another electrophysiological anomaly occurs when there is no return to the predrive normal cycle length after pharmacological neurotomy. In the secondary phase there may appear sinoauricular blocks. They may depend on or appear independently of the effect of the vegetative nervous system. The new test allows a physiopathological classification of normal and pathological sinus node function.

[Sinoatrial and Intra-atrial Conductive Disorders. The Value of Recording the Sinus Node Potential]

Direct recording of the sinus node potential in the bipolar mode using two electrodes of a quadripolar recording catheter positioned in the region of the sinus node at the junction of the superior vena cava to the right atrium was performed in 24 patients. Asynchronous overdrive atrial pacing was carried out using Strauss 'technique. Pharmacological denervation was carried out using intravenous propranolol (0,02 mg/kg) and atropine (0,04 mg/kg) using Jose's technique. An intravenous injection of a bolus of 20 mg of ATP was given in 3 cases. The sinus potential was identified by morphological criteria and confirmed after carotid sinus compression and atrial extrastimuli to exclude artefacts, especially the end of ventricular repolarisation of the preceding complex. The sinoatrial conduction time measured directly under basal conditions was considered normal when within 80 to 150 ms. Direct measurement of the sinus potential in the diagnosis of sinus node dysfunction seems to be less useful than the indirect techniques. On the other hand, it does confirm the diagnosis of sinoatrial block: five cases of special interest are described; in four cases the degree of sinoatrial block was variable: a significant increase of sinoatrial conduction time under basal conditions in 1 case; paroxysmal 3rd degree sinoatrial block revealed by programmed atrial stimulation in 2 cases; 2nd degree 2/1 sinoatrial block after injection of ATP in which the direct sinoatrial conduction time and sinus node function had been considered to be normal (1 case).(ABSTRACT TRUNCATED AT 250 WORDS)

[Reinterventions in Biliary Surgery]

Intracolonic By-pass: a New Technique to Prevent Anastomotic Complications in Colon and Rectal Surgery

A new technique, the "intracolonic bypass" designed to prevent anastomotic complications after colonic and rectal resections is reported. It consists of a latex tube fixed to the intestinal wall above the anastomosis, which prevents the fecal stream from reaching the anastomotic site. The tube is retained until complete healing of the anastomosis and then excreted spontaneously through the anus. This new and simple technique avoids the disadvantages of a temporary diverting ileostomy or colostomy.

[High Ligation of the Spermatic Vein in the Surgical Therapy of Varicocele. Our Experience]

[Intra-sinus Echo: Demonstration Using Direct Intracavitary Recording of the Sinus Potential]

The authors searched for intra-sinusal echos during electrophysiological investigation of 53 patients (41 men, 12 women, average age: 61 +/- 12 years). Cycles of sinus echos were recorded in 8 patients (15 per cent). The period during which sinus echos could be recorded was 125 ms (average 40.6 +/- 34 ms). Indirect assessment of sinus node function in patients with sinus echos was normal (corrected sinus node recovery time, estimated atrio-sino atrial conduction times using Narula's technique). A valid and reproducible direct recording of the sinus node potential was only possible in one patient. In this case the echo cycles were provoked by stimulation periods of between 440 and 320 ms (echo zone of 120 ms). All the echos obtained were preceded by a sinus node potential with a different duration and morphology to that observed during basal sinus cycles (respective sino-atrial conduction times 105 and 115 ms). In this patient we were also able to induce sinus echos after a single extrastimulus during the spontaneous rhythm. the echo zone was 130 ms and with a shorter coupling interval (310 ms) two successive sinus echos were recorded. The demonstration of intrasinusal echos by direct recording of the sinus node potential supports the experimental data of Allessie and Bonke on isolated right atrial tissues of the rabbit. Improvements in the technique of endocavitary direct recording of the sinus node potential in man should complete this data by showing the possibility of sinoatrial tachycardias due to reentry.

[Diagnostic Problems in the Physiopathological Characterization of Sinus Dysfunction]

Sino-atrial Dissociation: Evidence by Intracardiac Recordings in Man and by Microelectrode Studies on Isolated Rabbit Atrium

The electrophysiologic mechanisms of sinus dysfunction have recently been determined by direct recordings of the sinus node electrogram. The association of various degrees of abnormalities in the formation of the impulse within the sinus node and of sinoatrial conduction block, represents the pathophysiological substrate of the mechanism of sinus node dysfunction. The purpose of this work is to present clinical and experimental data supporting the concept of sinus node isolation. In our clinical case, the sinus node was probably intact despite aspects of sinus node dysfunction on the surface ECG. Sinus node electrograms were recorded with a sinoatrial conduction time of 100 ms (normal values in our laboratory: 83 ms +/- 38 ms). Atrial mapping demonstrated that the area depolarized by the sinus node involved a 2 cm2 zone surrounding it. This perisinusal activity could not be recorded on the surface ECG. Both exit and entry blocks in the sinus node were demonstrated. Our experimental data showed a total desynchronization between the electrical activity of the sinus node and that of the atrium under hypoxic conditions. Both types of cases demonstrated that an atrial dysrhythmia was coexisting with regular sinus activity. From these data we concluded that a sinus node free from any pathological involvement could be associated with severe symptoms of sinus node dysfunction on the surface ECG.

Intrinsic and Extrinsic Sinus Node Dysfunction: Diagnostic Problems

Based on clinical and experimental experience, pacemaker dysfunction in sick sinus syndrome can be differentiated into intrinsic and extrinsic. Sinus node activity is characterized electrophysiologically by automaticity, recovery and sinoatrial conduction. The automaticity of the sinus pacemaker cell groups and sinus recovery can be differentiated properly under experimental conditions. Studies of the electrophysiological characteristics have shown the basic functional parameters to be normal in extrinsic-autonomic sinus dysfunction. Diagnosis is either based on clinical observation or on the data of Holter monitoring, the electrophysiological methods being inadequate for diagnosing this neurovegetative form of sick sinus syndrome. On the other hand, intrinsic sinus dysfunction can be diagnosed by electrophysiological tests. If completed by complex pharmacological studies, in this organic form of sick sinus syndrome, even the severity of the intrinsic injuries can be assessed quantitatively. The above division provides a basis for selection and evaluation of the differential diagnostic procedures, while information on the aetiopathology of sinus dysfunction and on the degree of the functional injuries of the electrophysiological structure of the heart provides an adequate basis for therapy.

Coadministration of Flecainide Acetate and Sotalol During Pregnancy: Lack of Teratogenic Effects, Passage Across the Placenta, and Excretion in Human Breast Milk

[Value of Cibenzoline in the Preventive Treatment of Recurrent Atrial Arrhythmia]

Cibenzoline is a Vaughan-Williams class I anti-arrhythmic with properties intermediate between subclasses IA and IC which limit the incidence of proarrhythmic effects. These specific properties of the drug facilitate the prescription of cibenzoline in cardiology, particularly for the prevention of recurrent atrial arrhythmia: fibrillation, flutter, atrial tachycardia. This study demonstrates that cibenzoline is effective in these indications, since only 23% of the patients had relapsed after 6 months. This efficacy, combined with the good tolerance of the treatment, makes it possible to recommend the prescription of cibenzoline as a first-line treatment for the prevention of atrial arrhythmia. It represents an effective and safe option.

[Digitalis Poisoning in a Patient with Septic Shock: Value of Plasma Exchange]

[Criteria of Localization of the Bundle of Kent]

The high success rate (> 90%) of radiofrequency ablation of accessory pathways is related to accurate mapping. This determines the site of the accessory pathway and the best target for ablation with the object of reducing the number of applications and the associated morbidity. Analysis of the surface ECG is the first step of localisation of a Kent bundle. Different algorithms may be used based on the correlation between the polarity of the delta wave, of the QRS and the site of the accessory pathway confirmed at surgery or during radiofrequency ablation procedures. Some of the recent algorithms allow localisation of certain postero-septal or sub-epicardial pathways, the ablation of which can only be accomplished via the coronary sinus or one of its branches, or in an abnormally dilated coronary sinus, the so-called diverticulum. A relatively accurate localisation of the accessory pathway from the surface ECG reduces the duration of an ablation procedure and may economise the need for left-sided catheterisation. However, the endocavitary electrogrammes determine the precise target of ablation whether this be the ventricular or atrial pole of the bundle of Kent. The association of the criteria obtained by bipolar and unipolar recordings in sinus rhythm, during pacing or reentrant tachycardia enables accurate localisation in the majority of cases. Ablation of some pathways may be more complex because of their site or the presence of associated congenital or acquired cardiac disease which alters the anatomical or electrical markers. In these cases, the electrical criteria, especially those of the surface ECG may be erroneous and non invasive investigations such as Doppler echocardiography, isotopic ventriculography with phase analysis are most valuable with a positive predictive value of over 90%.

[Cost of Psychiatric Patients by Disability Type]

The study of the relation between treatment costs and disability of psychiatric patient groups.

Pilot Study of a Combination of Highly Active Antiretroviral Therapy and Cytokines to Induce HIV-1 Remission

A pilot study of a combination of highly active antiretroviral therapy (HAART) and cytokines in early HIV-1 infection has been undertaken to test the hypothesis that HIV-1 remission can be reached with this strategy by flushing latently infected viral reservoirs. Ten previously antiretroviral naive patients have received a combination of zidovudine, lamivudine, didanosine, saquinavir, and ritonavir for 72 weeks. Between weeks 12 and 48, three courses of interleukin (IL)-2 (7.5 millions of international units [MUI] twice a day for 5 consecutive days) and 2 courses of gamma-interferon (IFN) (100 microg every other day during 2 weeks) were administered subcutaneously. All patients reached plasma HIV-1 RNA levels < 20 copies/ml within 12 +/- 4 weeks. Transient increases in plasma levels (< 120 copies/ml) were observed during administration of IL-2, but less frequently during gamma-IFN administration. HIV-1 RNA decreased in lymph node cells by approximately 4 log, then remained stable after week 24. A mean drop of -0.8 log in peripheral blood mononuclear cell (PBMC) proviral DNA was observed during the trial. Isolation of potentially infectious HIV-1 was successful in each case by coculture of CD4+ T cells taken at week 72. The 2 patients who stopped therapy at the end of the trial showed rebounding plasma HIV-1 RNA levels within a few weeks. No additional mutations were selected in comparison with those present at baseline in 8 patients. In addition, 2 patients developed new mutations in the reverse transcriptase or protease gene and in 1 case, resistance selection was found in lymphoid tissue HIV-1 RNA but not in latently infected cells. In all cases, a rapid increase in both naive and memory CD4+ T cells was observed, with a reduction in activation markers and preservation of the CD8+CD28+ subset. Consequently, an aggressive regimen of HAART and cytokines administered in early stage disease is associated with a positive effect in terms of proviral load reduction and immune reconstitution but is unable to induce HIV-1 remission, allowing low levels of viral replication to persist in lymphoid reservoirs.

Enoxaparin As Adjunctive Antithrombin Therapy for ST-elevation Myocardial Infarction: Results of the ENTIRE-Thrombolysis in Myocardial Infarction (TIMI) 23 Trial

ENTIRE-TIMI 23 evaluated enoxaparin with full-dose tenecteplase (TNK) and half-dose TNK plus abciximab.

Myeloablative Therapy and Bone Marrow Transplantation in Jehovah's Witnesses with Malignancies: Single Center Experience

Hematological malignancies in Jehovah's Witnesses are often difficult to cure since these patients deny transfusions. By a retrospective analysis, we report the possibility of treating some tumors, mostly hematological, with either autologous or allogeneic bone marrow transplantation (BMT) without blood support. Eight patients were evaluated, including lymphoma (two patients), acute lymphoblastic (one patient) and myeloblastic (one patient) leukemia, chronic lymphocytic leukemia (one patient), refractory anemia with blasts in transformation (one patient), chronic myeloid leukemia (one patient) and metastatic breast cancer (one patient). All patients experienced a severe cytopenia with no major side effects or life-threatening complications. We had four deaths: three from relapse and progression of the disease (at 5, 8 and 15 months after the stem cell infusion), and one from acute intestinal GVHD (at 2 months after the stem cell infusion). Four patients are in complete clinical remission (at 8, 10, 16 and 26 months after the stem cell infusion), and this was related to the disease outcome. We conclude that autologous and allogeneic BMT are feasible without the support of transfusions. We believe that this should be performed as soon as possible in the course of the disease.

Hepatitis Viruses and HIV Infection in the Naples Area

In 189 anti-HIV positive subjects (130 males and 59 females; median age 32 years, range 17-57) we evaluated the prevalence of patients with hepatitis infections, the role of parenteral and sexual risk factors on the acquisition of these infections and the reciprocal influence between HIV and HCV infections. HCV infection was detected in 53.9% of cases and HBV infection in 8.4%. In only 32% of our patients no marker of hepatitis virus infection was detected. The presence of a hepatitis virus infection was associated to drug addiction; indeed in 91 drug abusers HIV/HCV co-infection was present in 80% of cases and HIV infection alone in 7.7%, p<0.0001. On the other hand, the association between unsafe sexual activity, whether homosexual or heterosexual, and sexual activity with a steady anti-HIV positive partner with HCV infection was less evident, although the high prevalence of anti-HCV in these cases (10.4%, 15.4% and 26.4% respectively) clearly suggests that HIV infection may improve the sexual transmission of HCV. No substantial differences in the level of immunodeficiency, nor in the HIV viral load nor in the frequency of AIDS cases were observed between patients with HIV infection alone and those with HIV/HCV co-infection. In fact, the percentage of patients with AIDS was similar in these two groups. However, we observed a statistically significant association between an advanced HIV clinical stage and the presence of HIV/HCV co-infection (p<0.005), since subjects with co-infection more frequently than with HIV infection alone were in the CDC-B clinical stage. The presence of a more severe liver disease was linked to a multiple hepatitis virus infection, regardless of the degree of immunodeficiency.

Helicobacter Spp. and Liver Diseases

To test whether Helicobacter species play a role in the enhancement of liver necro-inflammation and fibrosis and in the development of hepatocellular carcinoma (HCC), we sought DNA sequences of Helicobacter species in liver specimens from patients with viral-related chronic hepatitis, HCC or metastatic liver carcinoma. We enrolled 28 consecutive patients with ultrasound evidence of hepatic nodule(s) on their first liver biopsy: 21 had histological evidence of HCC (Group I) and 7 of metastatic liver carcinoma (Group II). In the same period we observed 27 consecutive patients with chronic hepatitis on their first liver biopsy (Group III). Helicobacter sequences were sought by PCR using primers for the 16S rDNA of Helicobacter spp, designed to amplify a 400 base-pair fragment, and detected by 2% agarose gel and hybridization with a specific biotinylated probe. We used, as positive controls for the DNA extraction from liver tissue, hepatic biopsy sections in which HBV infection was confirmed by HBcAg positivity and in which we amplified HBV-DNA by specific primers; positive controls for the amplification of Helicobacter spp were obtained from gastric biopsy sections in which Helicobacter pylori infection was confirmed by biochemical and histochemical tests. HBV-DNA was found in all five HBcAg positive liver biopsies. Helicobacter spp 16S rDNA was detected in all five biopsy specimens of gastric mucosa and in none of liver specimens from patients in any group. Our data suggest that Helicobacter species were not involved in the pathogenesis of virus-related HCC, chronic hepatitis or liver carcinoma metastasis.

Visualizing Sexual Dimorphism in the Brain

Sexually dimorphic behaviors are likely to involve neural pathways that express the androgen receptor (AR). We have genetically modified the AR locus to visualize dimorphisms in neuronal populations that express AR. Analysis of AR-positive neurons reveals both known dimorphisms in the preoptic area of the hypothalamus and the bed nucleus of the stria terminalis as well as novel dimorphic islands in the basal forebrain with a clarity unencumbered by the vast population of AR-negative neurons. This genetic approach allows the visualization of dimorphic subpopulations of AR-positive neurons along with their projections and may ultimately permit an association between neural circuits and specific dimorphic behaviors.

Lipodystrophy and Serum Lipid Abnormalities in HIV-positive Sub-Saharan Population on ART

To evaluate whether racial factors may be involved in the development of ART-induced lipodystrophy and/or lipid serum abnormalities, we carried-out a case-control study on all 23 consecutive anti-HIV-positive sub-Saharan black African patients observed from September 20fc01 to December 2001 ('Cases') and 23 Caucasian 'Controls' pair-matched for sex, age (+/-5 years), number of CD4 cells (+/-100 cells), clinical stage of HIV infection, overall duration (+/-3 months) of anti-retroviral treatment and type and duration (+/-3 months) of the last anti-retroviral regimen. The cases, as compared with the controls, less frequently showed lipodystrophy (4.4 vs. 65.2%, P<0.001) and hypertriglyceridemia (8.8 vs. 56.5%, P<0.005), whereas the prevalence of subjects with hypercholesterolemia was similar in the two groups (30 and 39.1%, respectively). Overall, the prevalence of patients lacking both lipodystrophy and serum lipid abnormalities was markedly higher for the cases than for the controls (69.5 vs. 13%, P<0.001). This study seems to indicate that anti-retroviral-induced lipodystrophy and hypertriglyceridemia may be associated to some racial factor.

Clinical and Virological Improvement of Hepatitis B Virus-related or Hepatitis C Virus-related Chronic Hepatitis with Concomitant Hepatitis A Virus Infection

We evaluated the clinical and virological characteristics of hepatitis A virus infection in persons concomitantly infected with hepatitis B virus (HBV) or hepatitis C virus (HCV).

Impact of Occult Hepatitis B Virus Infection in HIV Patients Naive for Antiretroviral Therapy

To study the impact of occult hepatitis B virus (HBV) infection in 115 consecutive anti-HIV-positive, hepatitis B surface antigen-negative patients, naive for antiretroviral treatment.

Interchromosomal Interactions and Olfactory Receptor Choice

The expression of a single odorant receptor (OR) gene from a large gene family in individual sensory neurons is an essential feature of the organization and function of the olfactory system. We have used chromosome conformation capture to demonstrate the specific association of an enhancer element, H, on chromosome 14 with multiple OR gene promoters on different chromosomes. DNA and RNA fluorescence in situ hybridization (FISH) experiments allow us to visualize the colocalization of the H enhancer with the single OR allele that is transcribed in a sensory neuron. In transgenic mice bearing additional H elements, sensory neurons that express OR pseudogenes also express a second functional receptor. These data suggest a model of receptor choice in which a single trans-acting enhancer element may allow the stochastic activation of only one OR allele in an olfactory sensory neuron.

Bone Marrow CD8 Cells Down-modulate Membrane IL-7Ralpha Expression and Exhibit Increased STAT-5 and P38 MAPK Phosphorylation in the Organ Environment

By comparing mature CD8-cell turnover in different organs, we previously demonstrated that CD8 cells proliferate predominantly in the bone marrow (BM). To investigate the mechanisms underlying such increased turnover, we compared BM, lymph nodes, and spleen CD8 cells from untreated C57BL/6 mice regarding in vivo proliferation within the organ; in vitro response to interleukin-7 (IL-7), IL-15, IL-21; ex vivo expression of membrane CD127 (IL-7Ralpha), intracellular Bcl-2, phospho-STAT-5 (signal transducer and activator of transcription 5), phospho-p38 mitogen activated protein kinase (MAPK); and in vivo proliferation on adoptive transfer. In the BM, the proliferation rate was increased for either total CD8 cells or individual CD44 and CD122 subsets. In contrast, purified CD8(+) cells from the BM did not show an enhanced in vitro proliferative response to IL-7, IL-15, and IL-21 compared with corresponding spleen cells. After transfer and polyinosinic-polycytidylic acid (polyI:C) treatment, both spleen-derived and BM-derived CD8 cells from congenic donors proliferated approximately twice more in the recipient BM than in spleen and lymph nodes. Our results suggest that BM CD8 cells are not committed to self-renewal, but rather are stimulated in the organ. Molecular events constantly induced in the CD8 cells within the BM of untreated mice include increase of both phosphorylated STAT-5 and phosphorylated p38 intracellular levels, and the reduction of CD127 membrane expression.

HPV Oral Infection. Case Report of an HIV-positive Nigerian Sex Worker

HPV infections have become a major problem in immunocompromised patients, particularly in HIV-positive subjects. HPV lesions are observed more frequently in the ano-genital area and rarely in different body areas, such as the skin and oral cavity. However, in HIV-positive subjects there is an increased risk of oral condylomas. We describe the case of an HIV-positive Nigerian young woman, who came to our notice due to the appearance of small labial and mouth mucous membrane lesions, related to HPV infection, as shown by a biopsy. These lesions were not evident in the genital area. After two years in which the patient no longer received therapy, there was a progressive reduction in CD4 count, associated with the development of the oral condylomas. Hence the patient began a new HAART combination, but after seven months, although a slight improvement emerged in the CD4 count with the disappearance of HIV-RNA, there has been no regression of oral condylomas.

Anti-HCV IgG Avidity Index in Acute Hepatitis C

The diagnosis of acute hepatitis C (AHC) is based on seroconversion to positive anti-HCV, which is usually not clinically possible.

Virological and Clinical Aspects of HBV-HCV Coinfection in HIV Positive Patients

In a long-term follow-up study the clinical and virological presentation of HBV/HCV coinfection in anti-HIV positive patients was evaluated. Plasma HBV-DNA, HCV-RNA, and HIV-RNA were determined by PCR in 5 HBsAg/anti-HCV/anti-HIV positive patients, in 4 HBsAg/anti-HIV positive patients and in 82 anti-HCV/anti-HIV positive patients first observed at a Unit of Infectious Diseases in Naples (Italy) from 1990 to 2000 (follow up 6-16 years). All five hepatitis B and C coinfected patients showed reciprocal inhibition of viral replication on admission and during the follow up. At the end of the follow up a clearance of HBsAg from serum was observed in four patients and a clearance of anti-HCV in one of them. In two patients after clearance of HBsAg, evidence of occult HBV infection was observed, at times associated with a hepatic flare. None of the four patients with HIV/HBV coinfection lost HBsAg and none of the 82 with HIV/HCV coinfection lost anti-HCV during the follow up. In anti-HIV positive patients HBV/HCV coinfection is characterized by reciprocal inhibition of viral replication, more evident in HBV expression in plasma and at times by progression to occult HBV infection.

Functional Specializations in Lateral Prefrontal Cortex Associated with the Integration and Segregation of Information in Working Memory

Control processes are thought to play an important role in working memory (WM), by enabling the coordination, transformation, and integration of stored information. Yet little is known about the neural mechanisms that subserve such control processes. This study examined whether integration operations within WM involve the activation of distinct neural mechanisms within lateral prefrontal cortex (PFC). Event-related functional magnetic resonance imaging was used to monitor brain activity while participants performed a mental arithmetic task. In the integration (IN) condition, a WM preload item had to be mentally inserted into the last step of the math problem. This contrasted with the segregation (SG) condition, which also required maintenance of the WM preload while performing mental arithmetic but had no integration requirement. Two additional control conditions involved either ignoring the preload (math only condition) or ignoring the math problem (recall only condition). Left anterior PFC (Brodmann's Area [BA] 46/10) was selectively engaged by integration demands, with activation increasing prior to, as well as during the integration period. A homologous right anterior PFC region showed selectively increased activity in the SG condition during the period in which the math problem and preload digit were reported. Left middorsolateral PFC regions (BA 9/46) showed increased, but equivalent, activity in both the SG and IN conditions relative to both control conditions. These results provide support for the selective role of lateral PFC in cognitive control over WM and suggest more specific hypotheses regarding dissociable PFC mechanisms involved during the integration and segregation of stored WM items.

Preparation for Integration: the Role of Anterior Prefrontal Cortex in Working Memory

The execution of complex working memory tasks often requires various cognitive control operations on stored content. Here we focus on the integration operation - defined as merging the outcome of subtask processing with additional information actively maintained before and during subtask execution. In prior work, we identified the anterior prefrontal cortex as critical for integration during mental arithmetic. Here we replicate and extend these results in an adapted mental arithmetic task that enabled examination of the detailed temporal dynamics of the anterior prefrontal activation. We find that this region is involved in the preparation for integration, possibly by ensuring that goal-relevant information is maintained in an accessible form, while at the same time protected from subtask interference.

[Epidemiology of Dog Bite Lesions]

Virological Pattern in Plasma, Peripheral Blood Mononuclear Cells and Liver Tissue and Clinical Outcome in Chronic Hepatitis B and C Virus Coinfection

BackgrounD: We aim to evaluate in chronic hepatitis B virus-hepatitis C virus (HBV-HCV) coinfection the interplay of these viruses in liver tissue, peripheral blood mononuclear cells (PBMC), and plasma and to analyze the effect on disease course and response to treatment.

Diagnosis and Clinical Impact of Occult Hepatitis B Infection in Patients with Biopsy Proven Chronic Hepatitis C: a Multicenter Study

Occult hepatitis B virus (HBV) infection in patients with chronic hepatitis C has been found associated with severe liver damage, low response to interferon treatment and increased risk of developing HCC. However, doubts remain on its clinical impact and the sensitivity and specificity of its detection. HBV-DNA was sought by PCR in plasma, peripheral blood mononuclear cells (PBMCs) and liver compartments of 89 patients with biopsy proven chronic hepatitis C, using sets of primers for core ("c"), surface ("s"), and x ("x") regions of HBV genome. Occult HBV infection was defined by the presence of HBV-DNA in at least two different PCRs in at least one compartment. Occult HBV infection was detected in 37 (41.6%) of the 89 patients investigated. It was more frequent (80.8%) in 26 anti- HBs negative/anti-HBc positive patients than in 18 anti-HBs/anti-HBc positive (61.1%, P < 0.01) and 45 anti-HBs/anti-HBc negative (11.1%, P < 0.0001), and more frequently in liver (91.9%) than in PBMCs (62.2%) and plasma (32.4%). No association was found between occult HBV infection and the degree of liver necroinflammation and fibrosis. However, considering the 52 patients without occult HBV infection, 51.4% of 35 patients with genotype 1 and 5.9% of 17 with genotype non-1 showed severe fibrosis (P = 0.003); patients with occult HBV infection did not show such difference. Instead of seeking occult HBV infection in patients with chronic hepatitis C, both anti-HBs negative/anti-HBc positive and anti-HBs positive/anti-HBc positive, in plasma alone, more reliable information can also be obtained from the liver tissue and PBMCs.

The MINERVA Study Design and Rationale: a Controlled Randomized Trial to Assess the Clinical Benefit of Minimizing Ventricular Pacing in Pacemaker Patients with Atrial Tachyarrhythmias

Dual-chamber (DDD) pacing has generally been regarded as "physiologic pacing" and therefore expected to be superior to ventricular pacing. Major randomized trials have so far failed to demonstrate significant reductions in the incidences of mortality, stroke, and heart failure. It has been shown that unnecessary ventricular pacing in patients with sinus node dysfunction or only intermittent atrioventricular block is associated with ventricular desynchronization and increased risk of atrial tachyarrhythmias (ATA).

Comparison of Endoscopic and Microscopic Removal of Pituitary Adenomas: Single-surgeon Experience and the Learning Curve

The endoscopic endonasal approach for resection of pituitary lesions is an effective surgical option for tumors of the sella turcica. In this study the authors compared outcomes after either purely endoscopic resection or traditional microscope-aided resection. They also attempted to determine the learning curve associated with a surgical team converting to endoscopic techniques.

Improvement in the Aetiological Diagnosis of Acute Hepatitis C: a Diagnostic Protocol Based on the Anti-HCV-IgM Titre and IgG Avidity Index

The gold standard for the diagnosis of acute hepatitis C (AHC) is seroconversion to anti-HCV/HCV-RNA positivity, an occurrence frequently missed in clinical practice.

Factors Affecting the Changes in Molecular Epidemiology of Acute Hepatitis B in a Southern Italian Area

To explore changes in molecular epidemiology of acute viral hepatitis B (AVH-B), hepatitis B virus (HBV) genotypes were determined by direct sequencing of the Pre-S-S region in 123 consecutive patients, with AVH-B observed in Naples or its surroundings in the last decade (group AVH-B) and in 123 HBV chronic carriers [chronic carrier of HBV (CC-B) group] from the same areas, who had been hepatitis B surface antigen-positive for more than 10 years. Genotype D was less frequently detected in patients with AVH-B than in those in the CC-B group (76.4%vs 97.5%, P < 0.0001). In the AVH-B group, intravenous drug addiction (IVDA) was the prevalent risk factor (55.3%) for acquiring HBV in the 94 patients with HBV genotype D, but it was rarely recorded (6.9%) in the 29 patients with genotypes non-D (P < 0.0001); unsafe sexual intercourse was prevalent in patients with genotype non-D (72.3%) and less frequent in those with genotype D (28.8%, P < 0.005). In the AVH-B group, the prevalence of non-D genotypes increased during the observation period from 11.1% in 1999-2003 to 41.1% in 2004-2008 (P < 0.0005), paralleling the increase in the prevalence of patients with unsafe sexual intercourse; similarly, the progressive decrease in IVDA paralleled the decrease in the prevalence of genotype D (from 88.3% in 1999-2003 to 11.7% in 2004-2008). The prevalence of HBV non-D genotypes recorded in the last 10 years in AVH-B in this area shows a progressive increase, most probably because of recent changes in HBV epidemiology, namely, the HBV mass vaccination campaign and increased immigration from areas with high HBV endemicity.

Backward Masking and Unmasking Across Saccadic Eye Movements

Humans make several eye movements every second, and thus a fundamental challenge in conscious vision is to maintain continuity by matching object representations in constantly shifting retinal coordinates. One possible mechanism for visual stability is the remapping of receptive fields around saccade onset, combining pre- and postsaccadic information. The mislocalization of stimuli briefly flashed near the time of saccades has been taken as evidence for remapping. Yet the relationship between remapping, mislocalization, and trans-saccadic integration remains unclear. We asked participants to identify a target stimulus presented around the time of saccade onset, which was immediately visually masked by a postsaccadic stimulus presented in the same spatial location (backward masking). Presenting two rapidly occurring events across separate fixations allowed us to investigate how the visual system reconstructs what happens during a saccade. We show that saccadic remapping resulted in perception of target and mask as either spatially segregated or integrated, depending on the exact timing of saccade onset. During segregation, the target was unmasked because it was perceived as displaced from the mask; during integration, the postsaccadic stimulus masked the presaccadic target (spatiotopic masking). Thus, segregation and integration may work together to yield continuity in conscious vision.

Deep Brain Stimulation Compared with Bariatric Surgery for the Treatment of Morbid Obesity: a Decision Analysis Study

Roux-en-Y gastric bypass is the gold standard treatment for morbid obesity, although failure rates may be high, particularly in patients with a BMI > 50 kg/m(2). With improved understanding of the neuropsychiatric basis of obesity, deep brain stimulation (DBS) offers a less invasive and reversible alternative to available surgical treatments. In this decision analysis, the authors determined the success rate at which DBS would be equivalent to the two most common bariatric surgeries.

Together €¦ to Take Care: Multidisciplinary Management of Hepatitis C Virus Treatment in Randomly Selected Drug Users with Chronic Hepatitis

Hepatitis C Virus (HCV) infection is treated with peg-interferon α2a or α2b and ribavirin. International studies show that drug user adherence to treatment is 40% to 60% and increases if the patient is in addiction treatment. The aim of the Together To Take Care (TTTC) study was to achieve better adherence to HCV therapy in randomly selected drug users, who are considered "difficult to treat." The secondary aim of the TTTC Study Group was to standardize a method for a multidisciplinary management of the liver disease in drug users. The TTTC group data were matched with a control group. Adherence: The 93.7% of patients followed therapy prescribed; of the patients infected by HCV genotype (gt) 3, all completed therapy as scheduled. For the 48-week treatment group, 66.7% of patients completed therapy (2 of 9 patients stopped treatment for breakthrough). Toxicological results: 10 (62.5%) patients were negative in the toxicological tests (opiates, cocaine, and alcohol). Virological results: 8 of 16 patients were infected by HCV gt 1, and 8 were infected by gt 3; 2 of 16 (12.5%) patients were human immunodeficiency virus (HIV) coinfected (1 HCV gt 1a and 1 HCV gt 3). All patients: 11 of 16 (68.75%) patients were HCV ribonucleic acid undetectable 24 weeks after completing therapy (sustained virological response, SVR). Gt 1: 4 of 8 (50.0%) showed SVR. Gt 3: 7 of 8 (87.5%) showed SVR. Overall, the HCV gt 3 patients had 87.5% probability of SVR, whereas gt 1 patients had 50% probability of SVR (gt 3/gt 1 patients odds ratio = 7). The results were analyzed by Fisher exact test. Our results show that good healthcare management plays an important role in increasing patients' adherence to therapy. In the project "TTTC," the patients work with the physicians to take responsibility for their health and acquire self-efficacy and self-awareness, thanks to the special care.

[Spontaneous Rectus Sheath Hematoma: a Rare Condition with Uneasy Diagnosis and Multidisciplinary Treatment. Report of 5 Cases and Review of Literature]

Spontaneous rectus sheath hematoma is a rare condition. It encompasses a wide spectrum of severity (self-limiting to fatal) depending of its size, etiology, and the development of complications. It enters into the differential diagnosis of abdominal pain but it's frequently difficult to diagnose and often radiologic imaging is required. Authors report a series of five patients admitted at emergency room within a 2-year period. Patient were between 63 to 78 years old. One of them was in therapy with warfarin, one was in therapy with acetilsalicililate and clopidogrel and in an another patient a coagulation disorder was detected. Diagnosis was suspected in all cases by clinical exam and ultrasonography, but CT-scan was necessary in three cases. All patients underwent conservative treatment, mainly pain relief and rest. In two cases blood transfusion was performed and in two cases clotting abnormalities were corrected with vitamin K and fresh frozen plasma. Average ospedalization was 10 days (range 5-17). One patient developed late seroma and was treated with ultrasound-guided aspiration. Rectus sheath hematoma is a rare but important entity in the differential diagnosis of abdominal pain. The difficulties in the correct diagnosis frequently lead to delay in treatment or unneeded surgery. CT-scan is the gold-standard investigation. Treatment options are variable and include conservative treatment, intravascular embolization and surgery Frequently an interdisciplinary team approach is needed.

Cerebral Revascularization for the Treatment of Complex Intracranial Aneurysms of the Posterior Circulation: Microsurgical Anatomy, Techniques and Outcomes

While the trend for endovascular therapy of posterior circulation aneurysms is permeating, cerebrovascular bypass remains essential in the armamentarium for complex lesions not amendable to these techniques. This review discusses the microsurgical anatomy of the posterior fossa intracranial circulation, as well as the techniques and outcomes related to cerebrovascular bypass.

Guidelines Issued by the French Society of Cardiology Concerning the Competence, Performance and Environment Required in the Practice of Diagnostic and Interventional Cardiac Electrophysiology

Salvage C2 Ganglionectomy After C2 Nerve Root Decompression Provides Similar Pain Relief As a Single Surgical Procedure for Intractable Occipital Neuralgia

OBJECTIVE: To determine the effectiveness of C2 nerve root decompression and C2 dorsal root ganglionectomy for intractable occipital neuralgia (ON) and C2 ganglionectomy after pain recurrence following initial decompression. METHODS: A retrospective review was performed of the medical records of patients undergoing surgery for ON. Pain relief at the time of the most recent follow-up was rated as excellent (headache relieved), good (headache improved), or poor (headache unchanged or worse). Telephone contact supplemented chart review, and patients rated their preoperative and postoperative pain on a 10-point numeric scale. Patient satisfaction and disability were also examined. RESULTS: Of 43 patients, 29 were available for follow-up after C2 nerve root decompression (n = 11), C2 dorsal root ganglionectomy (n = 10), or decompression followed by ganglionectomy (n = 8). Overall, 19 of 29 patients (66%) experienced a good or excellent outcome at most recent follow-up. Among the 19 patients who completed the telephone questionnaire (mean follow-up 5.6 years), patients undergoing decompression, ganglionectomy, or decompression followed by ganglionectomy experienced similar outcomes, with mean pain reduction ratings of 5 ± 4.0, 4.5 ± 4.1, and 5.7 ± 3.5. Of 19 telephone responders, 13 (68%) rated overall operative results as very good or satisfactory. CONCLUSIONS: In the third largest series of surgical intervention for ON, most patients experienced favorable postoperative pain relief. For patients with pain recurrence after C2 decompression, salvage C2 ganglionectomy is a viable surgical option and should be offered with the potential for complete pain relief and improved quality of life (QOL).

[Squamous-cell Carcinoma and Pilonidal Sinus Disease. Case Report and Review of Literature]

Squamous-cell carcinoma arising in a pilonidal sinus is a rare occasion. Authors report the case of a 60 years old male, with a 15 years history of recurrent pilonidal sinus disease. The patient underwent incisional biopsy, staging with total body CT, and finally radical surgery. The large wound healed by secondary intention, with a complete formation of the scar in three months. After six months, no complications or signs of recurrence were observed. Authors recommend careful inspection of the pilonidal area in all chronic and longstanding inflammatory lesions to identify promptly malignant transformation.

Lactate-to-pyruvate Ratio As a Marker of Propofol Infusion Syndrome After Subarachnoid Hemorrhage

Propofol infusion syndrome (PRIS) is a rare but frequently fatal condition. It is characterized by cardiovascular collapse and metabolic derangement due to propofol exposure. The pathophysiology of PRIS is poorly understood, and its study has previously been limited to animal models and clinical observations. We present the first in vivo brain biochemical data in a patient with PRIS.

Heterotopic Pancreatic Neoplasm Presenting As an Obstructing Mass at the Fourth Portion of the Duodenum

Heterotopic pancreatic adenocarcinoma is a rare finding at laparotomy. Herein we present the case of a patient with malignant transformation of a heterotopic pancreas located in the fourth portion of the duodenum.

Early Experience with Flow Diverting Endoluminal Stents for the Treatment of Intracranial Aneurysms

We aimed to identify the initial preliminary experience with flow diverting stents (FDS) for the treatment of intracranial aneurysms (IA). A PubMed search was performed to identify studies reporting patients treated with FDS. Selection was made for studies that provided either immediate or short term follow-up data. For each study, the number of patients and IA were identified. Details regarding the aneurysm itself were recorded; such as aneurysm morphology (saccular or fusiform), location, and rupture status. The primary treatment modality and the number of stents used to treat each aneurysm was recorded along with the antiplatelet regimen used. Outcomes such as aneurysm occlusion and complications, including stroke, in-stent thrombosis and stenosis, and death were identified. The average length of follow-up was calculated in weeks. A total of 10 manuscripts reporting 206 IA in 190 patients were identified in the literature. Occlusion rates were variably reported, ranging from 58% to 94% in the larger series. Major complications of treatment included stroke (6.0%), in-stent thrombosis and stenosis (4.9%), and death (3.3%). A phenomenon of delayed aneurysm rupture was also identified. We concluded that flow diverting stents have proven effective in a variety of scenarios. The major complications with FDS have related to perforator artery stroke, aneurysm re-rupture, and in-stent stenosis and thrombosis. Long-term efficacy, optimal antithrombotic agent regimen, and perforator stroke risk are yet to be determined.

Mechanisms of Rule Acquisition and Rule Following in Inductive Reasoning

Despite the recent interest in the neuroanatomy of inductive reasoning processes, the regional specificity within prefrontal cortex (PFC) for the different mechanisms involved in induction tasks remains to be determined. In this study, we used fMRI to investigate the contribution of PFC regions to rule acquisition (rule search and rule discovery) and rule following. Twenty-six healthy young adult participants were presented with a series of images of cards, each consisting of a set of circles numbered in sequence with one colored blue. Participants had to predict the position of the blue circle on the next card. The rules that had to be acquired pertained to the relationship among succeeding stimuli. Responses given by subjects were categorized in a series of phases either tapping rule acquisition (responses given up to and including rule discovery) or rule following (correct responses after rule acquisition). Mid-dorsolateral PFC (mid-DLPFC) was active during rule search and remained active until successful rule acquisition. By contrast, rule following was associated with activation in temporal, motor, and medial/anterior prefrontal cortex. Moreover, frontopolar cortex (FPC) was active throughout the rule acquisition and rule following phases before a rule became familiar. We attributed activation in mid-DLPFC to hypothesis generation and in FPC to integration of multiple separate inferences. The present study provides evidence that brain activation during inductive reasoning involves a complex network of frontal processes and that different subregions respond during rule acquisition and rule following phases.

EBP1 and DRBP76/NF90 Binding Proteins Are Included in the Major Histocompatibility Complex Class II RNA Operon

Major histocompatibility complex class II mRNAs encode heterodimeric proteins involved in the presentation of exogenous antigens during an immune response. Their 3'UTRs bind a protein complex in which we identified two factors: EBP1, an ErbB3 receptor-binding protein and DRBP76, a double-stranded RNA binding nuclear protein, also known as nuclear factor 90 (NF90). Both are well-characterized regulatory factors of several mRNA molecules processing. Using either EBP1 or DRBP76/NF90-specific knockdown experiments, we established that the two proteins play a role in regulating the expression of HLA-DRA, HLA-DRB1 and HLA-DQA1 mRNAs levels. Our study represents the first indication of the existence of a functional unit that includes different transcripts involved in the adaptive immune response. We propose that the concept of 'RNA operon' may be suitable for our system in which MHCII mRNAs are modulated via interaction of their 3'UTR with same proteins.

Increased D-aspartate Brain Content Rescues Hippocampal Age-related Synaptic Plasticity Deterioration of Mice

Until recently, free d-amino acids were thought to be involved only in bacterial physiology. Nevertheless, today there is evidence that D-serine, by acting as co-agonist at NMDARs, plays a role in controlling neuronal functions in mammals. Besides D-serine, another D-amino acid, D-aspartate (D-Asp), is found in the mammalian brain with a temporal gradient of occurrence: high in embryo and low in adult. In this study, we demonstrate that D-Asp acts as an endogenous NMDAR agonist, since it triggers currents via interaction with each of NR2A-D receptor subunits. According to its pharmacological features, we showed that oral administration of D-Asp strongly enhances NMDAR-dependent LTP in adulthood and, in turn, completely rescues the synaptic plasticity decay observed in the hippocampus of aged animals. Therefore, our findings suggest a tantalizing hypothesis for which this in-embryo-occurring D-amino acid, when "forced" over its physiological content, may disclose plasticity windows inside which it counteracts the age-related reduction of NMDAR signaling.

Unconscious Priming Instructions Modulate Activity in Default and Executive Networks of the Human Brain

During task executions, brain activity increases in executive networks (ENs) and decreases in default-mode networks (DMNs). Here, we examined whether these large-scale network dynamics can be influenced by unconscious cognitive information processing. Volunteers saw instructions (cues) to respond either ipsilaterally or contralaterally to a subsequent lateralized target. Unbeknownst to them, each cue was preceded by a masked stimulus (prime), which could be identical (congruent), or opposite (incongruent) to the cue, or neutral (not an instruction). Behaviorally, incongruent primes interfered with performance, even though they were not consciously perceived. With functional magnetic resonance imaging, we individuated the anticorrelated ENs and DMNs involved during task execution. With effective connectivity analyses, we found that DMNs caused activity in ENs throughout the task. Unconscious interference during incongruent trials was associated with a specific activity increase in ENs and an activity drop in DMNs. Intersubject efficiency in performance during incongruent trials was correlated with functional connectivity between specific ENs and DMNs. These results indicate that unconscious instructions can prime activity in ENs and DMNs and suggest that the DMNs play a key role in unconscious monitoring of the environment in the service of efficient resource allocation for task execution.

An Atypical Morphologic Presentation of Coccidioides Spp. in Fine-needle Aspiration of Lung

Infection due to Coccidioides spp., a dimorphic fungal pathogen, usually presents as a chronic pulmonary disease, occasionally with pulmonary nodules. On cytology, large spherules filled with endospores are typically seen. We report an unusual case of coccidioidomycosis in a 39-year-old female from an area nonendemic for Coccidioides and without other known risk factors for infection. Fine-needle aspiration of the patient's cavitary lung lesion revealed Coccidioides spp., which demonstrated atypical delicate septate hyphal forms and chains of conidia, with none of the large spherules typical of Coccidioides spp. Atypical hyphal and other forms of Coccidioides spp. have been reported in several studies, primarily from biopsy or tissue resection specimens. However, this is the first case to our knowledge that the organism has presented solely as conidial and atypical hyphal forms in an aspirated specimen. Pathologists who are unfamiliar with this atypical hyphal formation may misdiagnose the organism as several different fungi, including Aspergillus spp. or Fusarium spp. It is important to differentiate among fungi, as antifungal treatments may vary. Cytologists should be aware of the diverse morphologies demonstrated by Coccidioides spp. and include this organism in their differential diagnosis, even in patients seemingly devoid of pertinent risk factors.

A Mechanistic Role for Type III IFN-λ1 in Asthma Exacerbations Mediated by Human Rhinoviruses

Human rhinoviruses (HRV) are the leading cause of upper respiratory infections and have been postulated to trigger asthma exacerbations. However, whether HRV are detected during crises because upper respiratory infections often accompany asthma attacks, or because they specifically elicit exacerbations, is unclear. Moreover, although several hypotheses have been advanced to explain virus-induced exacerbations, their mechanism remains unclear.

Microthrombosis After Experimental Subarachnoid Hemorrhage: Time Course and Effect of Red Blood Cell-bound Thrombin-activated Pro-urokinase and Clazosentan

Delayed cerebral ischemia (DCI) is a significant cause of morbidity and mortality for patients surviving the rupture of an intracranial aneurysm. Despite an association between vasospasm and DCI, thrombosis and thromboembolism may also contribute to DCI. In this study we investigate the time course of intravascular microclot formation after experimental subarachnoid hemorrhage (SAH) and assess the effects of the following two drugs on microclot burden: mutant thrombin-activated urokinase-type plasminogen activator (scFv/uPA-T), which is bound to red blood cells for use as a thromboprophylactic agent, and clazosentan, an endothelin antagonist. In the first study, adult male C57BL/6 mice were sacrificed at 24 (n=5), 48 (n=6), 72 (n=8), and 96 (n=3) hours after SAH induced by filament perforation of the anterior cerebral artery. Sham animals (n=5) underwent filament insertion without puncture. In the second study, animals received scFv/uPA-T (n=5) 3 hours after hemorrhage, clazosentan (n=5) by bolus and subcutaneous pump after SAH just prior to skin closure, or a combination of scFv/uPA-T and clazosentan (n=4). Control (n=6) and sham (n=5) animals received saline alone. All animals were sacrificed at 48 hours and underwent intra-cardiac perfusion with 4% paraformaldehyde. The brains were then extracted and sliced coronally on a cryostat and processed for immunohistochemistry. An antibody recognizing thrombin-anti-thrombin complexes was used to detect microclots on coronal slices. Microclot burden was calculated for each animal and compared among groups. Following SAH, positive anti-thrombin staining was detected bilaterally in the following brain regions, in order of decreasing frequency: cortex; hippocampus; hypothalamus; basal ganglia. Few microclots were found in the shams. Microclot burden peaked at 48 hours and then decreased gradually. Animals receiving scFv/uPA-T and scFv/uPA-T+clazosentan had a lower microclot burden than controls, whereas animals receiving clazosentan alone had a higher microclot burden (p<0.005). The overall mortality rate in the time course study was 40%; mortality was highest among control animals in the second study. Intravascular microclots form in a delayed fashion after experimental SAH. Microclots may be safely reduced using a novel form of thromboprophylaxis provided by RBC-targeted scFv/uPA-T and represent a potential target for therapeutic intervention in the treatment of DCI.

Deep Brain Stimulation Compared with Methadone Maintenance for the Treatment of Heroin Dependence: a Threshold and Cost-effectiveness Analysis

To determine the success threshold at which a theoretical course of deep brain stimulation (DBS) would provide the same quality of life (QoL) and cost-effectiveness for heroin dependence as methadone maintenance treatment (MMT).

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