Enhancement of semantic integration reasoning by tRNS.

The right hemisphere is involved with the integrative processes necessary to achieve global coherence during reasoning and discourse processing. Specifically, the right temporal lobe has been proven to facilitate the processing of distant associate relationships, such as generating novel ideas. Previous studies showed a specific swing of alpha and gamma oscillatory activity over the right parieto-occipital lobe and the right anterior temporal lobe respectively, when people solve semantic problems with a specific strategy, i.e., insight problem-solving. In this study, we investigated the specificity of the right parietal and temporal lobes for semantic integration using transcranial Random Noise Stimulation (tRNS). We administered a set of pure semantics (i.e., Compound Remote Associates [CRA]) and visuo-semantic problems (i.e., Rebus Puzzles) to a sample of 31 healthy volunteers. Behavioral results showed that tRNS stimulation over the right temporal lobe enhances CRA accuracy (+12%), while stimulation on the right parietal lobe causes a decrease of response time on the same task (-2,100 ms). No effects were detected for Rebus Puzzles. Our findings corroborate the involvement of the right temporal and parietal lobes when solving purely semantic problems but not when they involve visuo-semantic material, also providing causal evidence for their postulated different roles in the semantic integration process and promoting tRNS as a candidate tool to boost verbal reasoning in humans.

Predictors of immunodeficiency-related death in a cohort of low-income people living with HIV: a competing risks survival analysis.

We conducted a survival analysis with competing risks to estimate the mortality rate and predictive factors for immunodeficiency-related death in people living with HIV/AIDS (PLWH) in northeast Brazil. A cohort with 2372 PLWH was enrolled between July 2007 and June 2010 and monitored until 31 December 2012 at two healthcare centres. The event of interest was immunodeficiency-related death, which was defined based on the Coding Causes of Death in HIV Protocol (CoDe). The predictor variables were: sociodemographic characteristics, illicit drugs, tobacco, alcohol, nutritional status, antiretroviral therapy, anaemia and CD4 cell count at baseline; and treatment or chemoprophylaxis for tuberculosis (TB) during follow-up. We used Fine & Gray's model for the survival analyses with competing risks, since we had regarded immunodeficiency-unrelated deaths as a competing event, and we estimated the adjusted sub-distribution hazard ratios (SHRs). In 10 012·6 person-years of observation there were 3·1 deaths/100 person-years (2·3 immunodeficiency-related and 0·8 immunodeficiency-unrelated). TB (SHR 4·01), anaemia (SHR 3·58), CD4 <200 cells/mm3 (SHR 3·33) and being unemployed (SHR 1·56) were risk factors for immunodeficiency-related death. This study discloses a 13% coverage by highly active antiretroviral therapy (HAART) in our state and adds that anaemia at baseline or the incidence of TB may increase the specific risk of dying from HIV-immunodeficiency, regardless of HAART and CD4.

'Emotional Intelligence': Lessons from Lesions.

'Emotional intelligence' (EI) is one of the most highly used psychological terms in popular nomenclature, yet its construct, divergent, and predictive validities are contentiously debated. Despite this debate, the EI construct is composed of a set of emotional abilities - recognizing emotional states in the self and others, using emotions to guide thought and behavior, understanding how emotions shape behavior, and emotion regulation - that undoubtedly influence important social and personal outcomes. In this review, evidence from human lesion studies is reviewed in order to provide insight into the necessary brain regions for each of these core emotional abilities. Critically, we consider how this neuropsychological evidence might help to guide efforts to define and measure EI.

Validity of Italian adaptation of the Dizziness Handicap Inventory (DHI) and evaluation of the quality of life in patients with acute dizziness.

The impact of dizziness on Quality of Life (QoL) can be assessed by the Dizziness Handicap Inventory (DHI), which is used as a discriminative and evaluative tool. Although the DHI is available in several languages, an equivalent version for the Italian population is not yet available. Aim of this study was to translate the DHI into the Italian language (DHI-I), assess its correlation to the Italian version of the Short Form-36 Health Survey and to investigate its reliability in evaluating the QoL of patients with acute dizziness. The study population consisted of 50 patients (76% females and 24% males), mean age 51.6 years, range 25-85 years (SD = 14.5). A cross-sectional design was used to examine the internal consistency (Cronbach's α) and concurrent validity (Pearson's product moment correlation r). The application followed the stages of translation from English to Italian and linguistic adaptation, grammatical and idiomatic equivalence review. To confirm the external validity of DHI-I, the Pearson correlation test between the total score and single subscales of DHI-I and the 8 scales of the Short Form Health Survey (SF-36) was performed. The Cronbach α coefficients for internal consistency were 0.92 for the DHI-I and 0.82, 0.84 and 0.75 for the sub-scale functional, emotional and physical, respectively. The frequency distribution of no one item showed a percentage higher than 75% in a single possible answer (0, 2, 4), excluding a ceiling or floor effect. Correlations with the total score of DHI-I were consistent and the correlation between total score of DHI-I and total score on SF-36 was -0.593. Of the single subscales, the emotional scale showed a closer correlation with almost all scales of the SF-36. The correlation between the total score of SF-36 and the single sub-scale of DHI-I (functional, emotional, physical) were respectively -0.599, -0.563, -0.398. The DHI was culturally and linguistically adapted for its application in the Italian population. The DHI-I demonstrated a good reliability and is recommended as a measure of disability in patients with dizziness and unsteadiness. According to the DHI-I, patients with acute dizziness and with a clinical diagnosis of vestibular syndrome presented a decreased QoL; the physical aspects were the most compromised.

Two clusters of human infection with influenza A/H5N1 virus in the Republic of Azerbaijan, February-March 2006.

Following the appearance of influenza A/H5 virus infection in several wild and domestic bird species in the Republic of Azerbaijan in February 2006, two clusters of potential human avian influenza due to A/H5N1 (HAI) cases were detected and reported by the Ministry of Health (MoH) to the World Health Organization (WHO) Regional Office for Europe during the first two weeks of March 2006. On 15 March 2006, WHO led an international team, including infection control, clinical management, epidemiology, laboratory, and communications experts, to support the MoH in investigation and response activities. As a result of active surveillance, 22 individuals, including six deaths, were evaluated for HAI and associated risk infections in six districts. The investigations revealed eight cases with influenza A/H5N1 virus infection confirmed by a WHO Collaborating Centre for Influenza and one probable case for which samples were not available. The cases were in two unrelated clusters in Salyan (seven laboratory confirmed cases, including four deaths) and Tarter districts (one confirmed case and one probable case, both fatal). Close contact with and de-feathering of infected wild swans was considered to be the most plausible source of exposure to influenza A/H5N1 virus in the Salyan cluster, although difficulties in eliciting information were encountered during the investigation, because of the illegality of some of the activities that might have led to the exposures (hunting and trading in wild birds and their products). These cases constitute the first outbreak worldwide where wild birds were the most likely source of influenza A/H5N1 virus infection in humans. The rapid mobilisation of resources to contain the spread of influenza A/H5 in the two districts was achieved through collaboration between the MoH, WHO and its international partners. Control activities were supported by the establishment of a field laboratory with real-time polymerase chain reaction (RT-PCR) capacity to detect influenza A/H5 virus. Daily door-to-door surveillance undertaken in the two affected districts made it unlikely that human cases of influenza A/H5N1 virus infection remained undetected.

Two clusters of human infection with influenza A/H5N1 virus in the Republic of Azerbaijan, February-March 2006.

Following the appearance of influenza A/H5 virus infection in several wild and domestic bird species in the Republic of Azerbaijan in February 2006, two clusters of potential human avian influenza due to A/H5N1 (HAI) cases were detected and reported by the Ministry of Health (MoH) to the World Health Organization (WHO) Regional Office for Europe during the first two weeks of March 2006. On 15 March 2006, WHO led an international team, including infection control, clinical management, epidemiology, laboratory, and communications experts, to support the MoH in investigation and response activities. As a result of active surveillance, 22 individuals, including six deaths, were evaluated for HAI and associated risk infections in six districts. The investigations revealed eight cases with influenza A/H5N1 virus infection confirmed by a WHO Collaborating Centre for Influenza and one probable case for which samples were not available. The cases were in two unrelated clusters in Salyan (seven laboratory confirmed cases, including four deaths) and Tarter districts (one confirmed case and one probable case, both fatal). Close contact with and de-feathering of infected wild swans was considered to be the most plausible source of exposure to influenza A/H5N1 virus in the Salyan cluster, although difficulties in eliciting information were encountered during the investigation, because of the illegality of some of the activities that might have led to the exposures (hunting and trading in wild birds and their products). These cases constitute the first outbreak worldwide where wild birds were the most likely source of influenza A/H5N1 virus infection in humans. The rapid mobilisation of resources to contain the spread of influenza A/H5 in the two districts was achieved through collaboration between the MoH, WHO and its international partners. Control activities were supported by the establishment of a field laboratory with real-time polymerase chain reaction (RT-PCR) capacity to detect influenza A/H5 virus. Daily door-to-door surveillance undertaken in the two affected districts made it unlikely that human cases of influenza A/H5N1 virus infection remained undetected.

Therapeutic use of a long-term cytotoxic T cell line recognizing a common tumour-associated antigen: the pattern of in vitro reactivity predicts the in vivo effect on different tumours.

A long-term-cultured cytotoxic T lymphocyte (CTL) line (E/88) was obtained from splenic lymphocytes of BALB/c (H-2d) mice bearing the weakly immunogenic colonic carcinoma C26. This line was shown to be alpha/beta TCR + V beta 6 + CD3 + CD8 + CD4- and to recognize a common tumour-associated antigen on syngeneic carcinomas and sarcomas in a major-histocompatibility--complex-restricted and T-cell-receptor(TCR)-mediated fashion. The assessment of cytotoxic activity on a panel of 30 normal and neoplastic target cells of differing etiology and histo-type showed that E/88 CTL lysed syngeneic colon carcinomas and some fibrosarcomas but not leukemias, lymphomas or mammary carcinomas. Clones derived from the E/88 line exhibited the same lytic pattern. Moreover, anti-T3, anti-Lyt2.2, anti-alpha/beta TCR and anti-V beta 6 mAbs as well as anti-H-2d antisera abolished cytotoxicity when used in blocking experiments. The therapeutic activity of E/88 CTL upon in vivo transfer was assessed in mice bearing either experimental or spontaneous metastases of C26. In both models therapy with E/88 lymphocytes in combination or not with interleukin-2 was highly effective. Adoptive immunotherapy carried out with two clones obtained from line E/88 showed comparable therapeutic effects. In addition, treatment of syngeneic mice bearing experimental metastases of in vitro E/88-lysable or E/88-resistant tumours, showed that E/88 CTL can eradicate metastases of the former but not of the latter neoplasms. These data indicate that long-term CTL lines recognizing common tumour-associated antigens can be derived from tumour-bearing animals and used in adoptive immunotherapy of tumours previously shown to be lysed in vitro by these effectors.

Adjuvant adoptive immunotherapy with IL2 and lymphocytes from tumor-bearing mice: in vitro tumor-stimulated lymphocytes are more effective than LAK cells.

In order to determine whether lymphocytes with therapeutic potential can be obtained from colon carcinoma (C26)-bearing (TB) mice, splenocytes were activated either in mixed lymphocyte-tumor cell (MLTC) cultures in the presence of 5 and 10 U/ml IL2 or 250 and 100 U/ml IL2 (LAK effectors). The therapeutic efficacy, as well as functional and phenotypic features of such lymphocytes, was then compared in an adjuvant immunotherapy setting. Comparisons of the antigenic phenotype, cytotoxic and proliferative activities, and of transcription of different cytokine genes (IFN gamma, TNF alpha, IL4, IL6) between lymphocytes activated in MLTC and LAK failed to reveal major differences. However, the in vitro lysis of C26 by MLTC-activated but not by LAK TB lymphocytes was significantly blocked by anti-T3 and anti-Lyt2 monoclonal antibodies, suggesting that a fraction of specific antitumor effectors was present in the MLTC bulk population. Moreover, the amount of IFN gamma (but not of other cytokines) produced by MLTC-derived lymphocytes after stimulation with C26 cells was shown to be 10-fold higher than that produced by LAKs. When combined with low-dose IL2 administration as an adjuvant treatment in C26-operated mice, MLTC effectors showed a higher therapeutic activity than LAKs obtained from the same pool of lymphocytes from TB donors. In the same setting, MLTC-activated lymphocytes obtained from TB or tumor-excised (TE) mice, combined with IL2, were equally effective (76 and 74% survivors, respectively, vs. 27% of the surgery control group and 26% of the group given IL2 only), whereas LAK cells from TE but not from TB animals resulted in the cure of a significant fraction of mice.

Adoptive immunotherapy of a mouse colon carcinoma with recombinant interleukin-2 alone or combined with lymphokine-activated killer cells or tumor-immune lymphocytes. Survival benefit of adjuvant post-surgical treatments and comparison with experimental metastases model.

We have used a BALB/c colonic adenocarcinoma (C-26) to evaluate the therapeutic potential of recombinant interleukin-2 (rIL-2) at high and low dosages in combination with or without lymphokine-activated killers (LAK) or tumor-specific, immune lymphocytes in either an adjuvant spontaneous or an artificial metastasis system. Most (approximately 80%) of the mice that underwent s.c. C-26 tumor excision systemic treatment with low-dose rIL-2 (3 x 10(4) U/day, i.p.) increased the survival rate to 31% as compared to 21% (not significant) in excised controls while administration of high-dose rIL-2 (8 x 10(4) U/day) led to 53% survival (P less than 0.001). Both LAK cells and C-26-tumor-immune lymphocytes given during rIL-2-treatment significantly increased the effects of rIL-2 at the low but not at the high-dose, with tumor-immune effectors resulting in the highest percentage (63%) of cures. When mice bearing 3-day artificial lung metastases of C-26 cells were treated wtih low- or high-dose rIL-2, in combination with or without LAK or tumor-immune lymphocytes, a highly significant reduction or abrogation of the number of lung foci was observed with all treatments, including those involving or tumor-immune lymphocytes alone. Assessment of survival benefit in these mice, however, showed survival prolongation, with 20% cures achieved by low-dose rIL-2 alone and up to 65% cures by LAK in combination with low-dose rIL-2. In this system of artificial metastasis high-dose rIL-2 alone increased the survival time but failed to cure the animals, and the addition of LAK was ineffective whereas that of tumor-immune lymphocytes led to 80% cure. These results suggest that tumor-immune lymphocytes are more effective than LAK when combined with rIL-2 and that caution is necessary in extrapolating findings obtained in artificial metastasis models.

Adoptive immunotherapeutic treatments with interleukin 2 and lymphocytes in a mouse colonic adenocarcinoma model.

This article reports the results of adjuvant immunotherapy studies carried out in an experimental tumor model system. A transplantable murine BALB/c colonic adenocarcinoma (C-26) was used to evaluate the therapeutic potential of treatment with recombinant interleukin 2 (rIL-2) at high and low dosage in combination with or without lymphokine activated killer cells (LAK) or tumor-specific immune lymphocytes, either as an adjuvant treatment in mice bearing spontaneous post-surgical metastases or in mice bearing artificial metastases. Moreover the in vivo LAK activation and circulation pattern have been examined during or after treatment. These results show that cytotoxic lymphocytes from tumor-immunized donors are more active than LAKs when given in combination with rIL-2 as an adjuvant treatment, while all treatment modalities exerted a strong but generally transient inhibition on the formation of artificial lung metastases by C-26 cells. Alteration of host lymphocyte responsiveness to rIL-2 was shown to occur in early-tumor-resected and large-tumor-bearing animals in both in vitro and in vivo experiments. Moreover, no evidence of homing or preferential localization of the adoptively transferred LAK cells to the site of tumor growth was observed.

Influence of the donors' clinical status on in vitro and in vivo tumor-cytotoxic activation of interleukin-2-exposed lymphocytes and their circulation in different organs.

In-vitro-generated lymphokine-activated killer (LAK) cells of BALB/c mice, bearing the syngeneic colon carcinoma C-26 for 7 days, were as efficient as those from normal mice in lysing C-26 cells whereas LAK cells from 14-day tumor-bearing and 5- and 14-day tumor-resected animals had a lower C-26 cytotoxicity. The level of C-26 lysis returned to normal values 30 days after surgery. To identify the best source of LAK cells in vivo, groups of normal mice were treated with 10(4), 3 x 10(4) or 10(5) U/day of interleukin 2 (EL-2) for 7 days intraperitoneally (i.p.) or intravenously (i.v.) (3 x 10(4) dose only). The highest lysis on C-26 was obtained from peritoneal exudate cells of mice given 3 x 10(4) and 10(5) U whereas spleen cells were lytic only when taken from mice treated with 10(5) U IL-2. Peripheral blood lymphocytes lacked any cytotoxicity except for the group of mice which received IL-2 i.v. The kinetics of in vivo LAK activation in different organs showed a peak of anti-(C-26) lytic activity at day 5 in peritoneal exudate cells and spleen cells of mice given IL-2 for 5 days whereas administration of LAK cells alone had no effect: IL-2 plus LAK cells gave a lower peak of LAK activity as compared with IL-2 alone. A lower level of in vivo LAK activation was found in mice whose tumor was resected 5 days before; such impairment was evident even 14 days after surgery. Homing experiments were carried out with i.v. injected 51Cr-labelled LAK cells in normal or tumor-resected mice. In normal mice the highest radioactivity at 30 min was found in the lungs; liver and spleen also showed high radioactivity whereas blood had a negligible amount of radioactivity. Radioactivity declined rapidly in lungs (less than 10% after 24 h) while remaining at appreciable levels in the liver after 24 h and 48 h; spleen showed constant levels of 12%-15%. Homing of LAK cells was altered in mice receiving IL-2 i.p. for 5 days with slower and lower radioactivity peaks in the lung and higher levels in liver. In tumor-excised mice lower levels of radioactivity were found in lungs. These results show that: (a) alterations in LAK activity occur in early-tumor-resected and large-tumor-bearing animals; (b) the route of IL-2 administration is critical in LAK activation in vivo; (c) treatment with IL-2 modifies LAK homing.