The impact of nutritive and non-nutritive sweeteners on the central nervous system: preliminary study.

BACKGROUND: Human consumption of food and beverages containing added nutritive or non-nutritive sweeteners has increased worldwide. OBJECTIVE: The present study evaluated the possible impact of frequent sweetener consumption on human CNS activity and functions through neuropsychological testing and EEG/qEEG analysis. METHODS: A sample of 23 women and 16 men, aged 18-35, with a body mass index between 18 and 24.9 kg/m2 was evaluated. Participants underwent a 1-week washout period in which food with added sugars or sweeteners was restricted from their diet. Initial assessment of cognitive functions was performed with a validated neuropsychological test and EEG/qEEG analysis, prior to supplementation. Sucrose, sucralose, or steviol glycosides, in commercially available presentations, were randomly assigned to three experimental groups of 13 participants each. Sweeteners were supplemented in fixed amounts, daily, for six weeks. After supplementation, neurological tests were repeated and the initial and final results were compared. RESULTS: The results show no significant changes between final and initial measures in the steviol glycosides group. However, a significant decrease in encoding memory was found in the sucrose group in the final evaluation. Strikingly, the sucralose group showed a significant decrease in overall memory, encoding memory, and executive functions after supplementation. Furthermore, qEEG analysis showed an increase in theta wave absolute and relative power at the final evaluation in the same group. CONCLUSION: These data show that frequent consumption of specific sweeteners is accompanied by measurable changes in EEG/qEEG activity and neuropsychological test performance in humans.

The PI-3-Kinase P110α Catalytic Subunit of T Lymphocytes Modulates Collagen-Induced Arthritis.

The phosphatidylinositol 3-kinase (PI3K) family of enzymes plays a determinant role in inflammation and autoimmune responses. However, the implication of the different isoforms of catalytic subunits in these processes is not clear. Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease that entails innate and adaptive immune response elements in which PI3K is a potential hub for immune modulation. In a mouse transgenic model with T-cell-specific deletion of p110α catalytic chain (p110α-/-ΔT), we show the modulation of collagen-induced arthritis (CIA) by this isoform of PI3K. In established arthritis, p110α-/-ΔT mice show decreased prevalence of illness than their control siblings, higher IgG1 titers and lower levels of IL-6 in serum, together with decreased ex vivo Collagen II (CII)-induced proliferation, IL-17A secretion and proportion of naive T cells in the lymph nodes. In a pre-arthritis phase, at 13 days post-Ag, T-cell-specific deletion of p110α chain induced an increased, less pathogenic IgG1/IgG2a antibodies ratio; changes in the fraction of naive and effector CD4+ subpopulations; and an increased number of CXCR5+ T cells in the draining lymph nodes of the p110α-/-ΔT mice. Strikingly, T-cell blasts in vitro obtained from non-immunized p110α-/-ΔT mice showed an increased expression of CXCR5, CD44 and ICOS surface markers and defective ICOS-induced signaling towards Akt phosphorylation. These results, plus the accumulation of cells in the lymph nodes in the early phase of the process, could explain the diminished illness incidence and prevalence in the p110α-/-ΔT mice and suggests a modulation of CIA by the p110α catalytic chain of PI3K, opening new avenues of intervention in T-cell-directed therapies to autoimmune diseases.

PI3-Kinase p110α Deficiency Modulates T Cell Homeostasis and Function and Attenuates Experimental Allergic Encephalitis in Mature Mice.

Class I phosphoinositide 3-kinases (PI3K) are involved in the development of normal and autoimmune responses, including Experimental Autoimmune Encephalomyelitis (EAE), a mouse model for human multiple sclerosis (MS). Here, the role of the ubiquitously expressed class IA PI3K p110α catalytic subunits in EAE has been analyzed using a model of Cre/flox mediated T cell specific deletion of p110α catalytic chain (p110αΔT). Comparison of two month-old (young) and six month-old (mature) p110αΔT mice and their wild type (WT) counterparts indicated loss of spleen CD4+ T cells that increased with age, indicating a role of p110α in their homeostasis. In contrast, CD4+ T regulatory (Treg) cells were enhanced in mature p110αΔT mice when compared to WT mice. Since Myelin Oligodendrocyte Glycoprotein (MOG) peptide-induced EAE is dependent on, or mediated by CD4+ T cells and CD4+ T cell-derived cytokines and controlled by Treg cells, development of EAE in young and mature WT or p110αΔT mice was analyzed. EAE clinical symptoms and disease scores in six month p110αΔT mice were significantly lower than those of mature WT, or young WT and p110αΔT mice. Furthermore, ex vivo antigen activation of lymph node cells from MOG immunized mature p110αΔT mice induced significantly lower levels of IFN-γ and IL-17A than young p110αΔT or young and mature WT mice. Other cytokines including IL-2, IL-10 or TNF-α showed no significant differences between p110αΔT and WT mature mice. Our data show a lower incidence of MOG-induced EAE in mature p110αΔT mice linked to altered T cell homeostasis and lower secretion of inflammatory cytokines.

Characterization of the Sensorimotor Rhythm in 4-Month-Old Infants Born at Term and Premature.

The sensorimotor rhythm (SMR) is an electroencephalographic rhythm associated with motor and cognitive development observed in the central brain regions during wakefulness in the absence of movement, and it reacts contralaterally to generalized and hemibody movements. The purpose of this work was to characterize the SMR of 4-month-old infants, born either healthy at term or prematurely with periventricular leukomalacia (PVL). Two groups of infants were formed: healthy and premature with PVL. Their electroencephalograms (EEGs) were recorded in four conditions: rest, free movement, right-hand grasping and left-hand grasping, in order to explore general reactivity to free movement and contralateral reactivity in hand-grasping conditions. Associations between SMR, and cognitive and motor performance were analyzed. The healthy infants showed a SMR between 5.47 and 7.03 Hz, with clear contralateral reactivity to free movement and right-hand grasping. However, the premature infants with PVL did not show enough electroencephalographic characteristics to evidence the presence of SMR. Poor performance, characteristic of children with PVL, was related to low-frequency SMR, while good performance was associated with a higher frequency rhythm in the left hemisphere. The presence of SMR in the group of healthy infants could be considered a sign of health at this age. Thus, poor SMR evidence in the EEG of infants with PVL is probably a sign of brain immaturity or brain dysfunction. Our results provide data on infant SMR development that is needed to design neurofeedback protocols for infants with PVL.

Neurofeedback in Learning Disabled Children: Visual versus Auditory Reinforcement.

Children with learning disabilities (LD) frequently have an EEG characterized by an excess of theta and a deficit of alpha activities. NFB using an auditory stimulus as reinforcer has proven to be a useful tool to treat LD children by positively reinforcing decreases of the theta/alpha ratio. The aim of the present study was to optimize the NFB procedure by comparing the efficacy of visual (with eyes open) versus auditory (with eyes closed) reinforcers. Twenty LD children with an abnormally high theta/alpha ratio were randomly assigned to the Auditory or the Visual group, where a 500 Hz tone or a visual stimulus (a white square), respectively, was used as a positive reinforcer when the value of the theta/alpha ratio was reduced. Both groups had signs consistent with EEG maturation, but only the Auditory Group showed behavioral/cognitive improvements. In conclusion, the auditory reinforcer was more efficacious in reducing the theta/alpha ratio, and it improved the cognitive abilities more than the visual reinforcer.

[Electroencephalographic and neurodevelopmental disorders in severe congenital heart disease: A follow-up study]. / Alteraciones electroencefalográficas y del neurodesarrollo en cardiopatías congénitas severas. Estudio de seguimiento.

Congenital heart defects are the most common malformations at birth. Due to the fact that the developmental windows at early stages close rapidly, the aim of this study was to determine the impact of congenital heart defects on the central nervous system at short and medium terms after applying traditional and quantitative electroencephalography techniques and a test of neurodevelopment. Twenty-one patients (8-27 months, x = 14.8) with severe congenital heart defects who had been studied previously, and a control group of 19 healthy children (8-29 months, x = 14.6) were included. In all of them traditional electroencephalography, quantitative electroencephalography, and a test of neurodevelopment were performed. The results between groups (control vs. congenital heart defects) and between congenital heart defects (previous vs. present) were compared. In the second evaluation, congenital heart defect children maintained abnormal quantitative and traditional electroencephalography recordings. Comparing quantitative electroencephalography among congenital heart defects (previous vs. present) and between controls and congenital heart defects, significant differences of theta band activity in frontal, central, and temporal leads were found (p < 0.05). Upon assessing neurodevelopment, 86% of the previously studied congenital heart defect cases kept the same diagnosis of abnormality, of which mild-to-moderate hypotone was the most frequently observed. As hypothesized, congenital heart defect diseases have a very important impact on central nervous system function as determined by neurodevelopmental testing and traditional and quantitative electroencephalography recordings. The alterations observed persisted throughout the period studied.

Normative longitudinal EEG recordings during sleep stage II in the first year of age.

The electroencephalogram (EEG) is a fundamental diagnostic procedure that explores brain function. This manuscript describes the characteristics of a sample of healthy at-term infants. One hundred and three (103) infants from Mexico between 15 days and 12.5 months of age were recorded during physiological sleep. Referential EEG recordings were obtained using linked ear lobes as reference. The amplifier gain was 10,000, the bandwidth was set between 0.3 and 30 Hz, and the sample rate was 200 Hz. Sample windows of 2.56 s were marked for later quantitative analysis. To our knowledge, this is the first dataset of normal infants during the first year of age.

Neurobehavioral assessment of children presenting diverse congenital cardiopathologies.

Brain maturation in 1-36 month old children suffering from congenital cardiopathologies was assessed after a study of psychomotor development. The Rogers' test (Rogers et al., Developmental programming for infants and young children. Volume 2. Early intervention developmental profile, Revised edition, ESL/ELT Michigan, Ann Arbor, 1981) was applied to 65 children, of whom 21 presented with simple cardiopathologies (CpS) and 22 with complex cardiopathologies (CpC). All children were matched by age, sex and socioeconomic status to 22 healthy children in a control group (C). Mean differences between the three groups were established by applying the Kruskal-Wallis test, and mean differences between the C and CpS/CpC groups were determined using the Mann-Whitney test. The proportion of cases evaluated as "low" in each group was calculated by applying the Rogers' test, and a test of proportion differences was applied between the C and CpS/CpC groups. CpS children performed similarly to the C, whereas CpC children scored significantly lower than C children on all variables. It is highly likely that the suboptimal psychomotor performance observed in CpC children was due to compromised hemodynamics and related to subclinical immaturity of cerebral development.

[Incidence of congenital heart disease and factors associated with mortality in children born in two Hospitals in the State of Mexico]. / Incidencia de las cardiopatías congénitas y los factores asociados a la letalidad en niños nacidos en dos hospitales del Estado de México.

We studied the incidence, survival, and risk factors for mortality in a cohort of infants for a period of five years, born in two hospitals, one a second-level General Hospital, the second a tertiary perinatal hospital, both in the City of Toluca. The analysis of survival was performed with the Kaplan-Meier method, and Cox regression was used to estimate the risk of death according to different factors. We found an overall incidence of 7.4 per 1,000 live births; in preterm infants, the rate was 35.6 per 1,000, and in term newborns it was 3.68 per 1,000. The most common heart disease was the ductus arteriosus in the overall group and in preterm infants; in term newborns the most common was the atrial septal defect. The specific mortality was 18.64%, follow-up was 579 days, where we found, according to Kaplan-Meier, survival of an average of 437.92 days, with 95% confidence intervals of 393.25 to 482.6 days, with a standard error of 22.79 days; the cumulative probability of survival was 0.741, with a standard error of 0.44. In Cox regression, two variables had a high hazard ratio (HR): these were the presence or absence of cyanosis and the hospital where they were treated as newborns.

[Electroencephalographic and neurodevelopmental disorders in toddlers with severe congenital heart diseases. Preliminary study]. / Alteraciones electroencefalográficas y del neurodesarrollo en niños portadores de cardiopatías congénitas severas. Estudio preliminar.

UNLABELLED: Within the field of pediatric heart disease, congenital cardiopathology is the most important issue due to the fact that in these patients a delay of neurodevelopment is the most frequent morbidity. The major aim of this work was to determine the impact of severe congenital cardiopathology (SCC) on the central nervous system (CNS) through the study of the electroencephalogram (EEG) and the assessment of neurodevelopment. POPULATION AND METHODS: Children under 3 years old, 41 of them presenting SCC and 15 healthy controls (C) were studied. Conventional EEG recording and assessment of neurodevelopment were performed. RESULTS: In twenty children presenting SCC (48.8%) the EEG was found abnormal (paroxysmal of spikes and sharp waves). Forty of them (97.6%) presented neurodevelopmental alterations, including hypotonia and a delay in gross motor skills. When comparing EEG between SCC and C children, odds ratio was 13.33 (1.602-111) and comparing neurodevelopment delay, it was 35 (3.769-235). Both were statistically significant (p ≤ 0.00039 and p ≤ 0.00038, respectively). CONCLUSIONS: A high percentage of children suffering from SCC exhibited EEG patterns with abnormal epileptic-like activity although without clinical manifestation of seizures. These children also showed delay features in different areas of neurodevelopmental. The assessment of new born carrying some type of severe cardiopathology indicated that they were under high risk of suffering from CNS altered development.

Complement regulatory protein Crry/p65 costimulation expands natural treg cells with enhanced suppressive properties in proteoglycan-induced arthritis.

OBJECTIVE: To investigate the costimulatory role of Crry/p65 (Crry), a membrane complement regulatory protein, on the expansion and function of natural Treg cells and their ability to ameliorate proteoglycan-induced arthritis (PGIA), an animal model of inflammatory arthritis in which the role of natural Treg cells is not well established. METHODS: CD4+CD25+ natural Treg cells from BALB/c mice were activated in vitro and costimulated by Crry. The expanded cells were phenotypically characterized, and their suppressive effect on T cell proliferation was assayed in vitro. The potential prophylactic and therapeutic effects of this population versus those of natural Treg cells in PGIA were studied. The clinical score, histology, the antigen-specific isotype antibody pattern, in vitro T cell responses, and the presence of Treg cells in the paws were studied. RESULTS: Crry costimulation enhanced the in vitro expansion of natural Treg cells while maintaining their phenotypic and suppressive properties. Crry-expanded Treg cells had stronger suppressive properties in vivo and a longer ameliorating effect in the PGIA model than did natural Treg cells. Crry-expanded Treg cells suppressed T cell- and B cell-dependent responses in PGIA, changing the pathogenic antibody isotype pattern and decreasing antigen-dependent secretion of cytokines, including interferon-γ, interleukin-12 (IL-12), and IL-17. Increased FoxP3 expression was detected in the paws of mice transferred with Crry-expanded Treg cells. CONCLUSION: Crry-mediated costimulation facilitates in vitro expansion of natural Treg cells while maintaining their suppressive properties in vitro and in vivo in the PGIA model. These results highlight the potential of the complement regulatory protein Crry to costimulate and expand natural Treg cells capable of suppressing disease in an animal model of chronic inflammatory arthritis.

Biased binding of class IA phosphatidyl inositol 3-kinase subunits to inducible costimulator (CD278).

To better understand T lymphocyte costimulation by inducible costimulator (ICOS; H4; CD278), we analyzed proteins binding to ICOS peptides phosphorylated at the Y(191)MFM motif. Phosphorylated ICOS binds class IA phosphatidyl inositol 3-kinase (PI3-K) p85α, p50-55α and p85ß regulatory subunits and p110α, p110δ and p110ß catalytic subunits. Intriguingly, T cells expressed high levels of both p110α or p110δ catalytic subunits, yet ICOS peptides, cell surface ICOS or PI3-kinase class IA regulatory subunits preferentially coprecipitated p110α catalytic subunits. Silencing p110α or p110δ partially inhibited Akt/PKB activation induced by anti-CD3 plus anti-ICOS antibodies. However, silencing p110α enhanced and silencing p110δ inhibited Erk activation. Both p110α- and p110δ-specific inhibitors blocked cytokine secretion induced by TCR/CD3 activation with or without ICOS costimulus, but only p110α inhibitors blocked ICOS-induced cell elongation. Thus, p110α and p110δ are essential to optimal T cell activation, but their abundance and activity differentially tune up distinct ICOS signaling pathways.

Screening of neurodevelopmental delays in four communities of Mexico and Cuba.

OBJECTIVE: Nursing personnel applied a computerized evaluation instrument, Neuropediatric Development (NPED), and compared the prevalence of deviations from normal neurodevelopment in four communities of two Latin American countries, Mexico and Cuba. At the same time the feasibility of introducing this tool into Mexican local health centers was assessed. DESIGN AND SAMPLE: The NPED screening tool was applied to 400 children 1-60 months old from two suburban and one urban communities of Mexico and one urban community of Cuba. MEASURES: The NPED instrument was developed at the Neurosciences Centre of Cuba (Santos, & Pérez-Ábalo, 2011; Santos, Pérez-Abalo, & Álvarez, 2007), and explores three neurodevelopmental areas: language/communication, psychomotor, and sensory maturation (hearing/vision). RESULTS: Global (21.5%), language (16.5%), psychomotor (5.8%), and sensory (vision/audition; 2.3%/7%) failures were observed. Among Mexican communities, apart from the hearing test in which the urban community showed a significantly higher percentage of failures (p < .001), there were no other significant differences. When compared, the Cuban community showed a significantly higher proportion of audition failures in relation to the Mexican communities. CONCLUSIONS: The prevalence of deviations from normal neurodevelopment was highly similar between both countries, and the NPED system fulfils the necessary requisites for mass screening to be applied by nursing staff at a primary care level.

Role of endocytosis and trans-endocytosis in ICOS costimulator-induced downmodulation of the ICOS Ligand.

The interaction between the T-lymphocyte costimulatory molecule ICOS and its ligand (ICOS-L) is needed for efficient immune responses, but expression levels are tightly controlled, as altered expression of ICOS or ICOS-L may lead to immunodeficiency, or favor autoimmune diseases and tumor growth. Using cells of mouse B cell lymphoma (M12.C3) and melanoma (B16), or hamster CHO cells transfected with various forms of mouse ICOS-L, and ICOS+ T cell lines, we show that, within minutes, ICOS induces significant downmodulation of surface ICOS-L that is largely mediated by endocytosis and trans-endocytosis. So, after interaction with ICOS+ cells, ICOS-L was found inside permeabilized cells, or in cell lysates, with significant transfer of ICOS from ICOS+ T cells to ICOS-L-expressing cells, and simultaneous loss of surface ICOS by the T cells. Data from cells expressing ICOS-L mutants show that conserved, functionally important residues in the cytoplasmic domain of mouse ICOS-L (Arg300 , Ser307 and Tyr308 ), or removal of ICOS-L cytoplasmic tail have minor effect on its internalization. Internalization was dependent on temperature, and was partially dependent on actin polymerization, the GTPase dynamin, protein kinase C, or the integrity of lipid rafts. In fact, a fraction of ICOS-L was detected in lipid rafts. On the other hand, proteinase inhibitors had negligible effects on early modulation of ICOS-L from the cell surface. Our data add a new mechanism of control of ICOS-L expression to the regulation of ICOS-dependent responses.

Differential effects of the second SARS-CoV-2 mRNA vaccine dose on T cell immunity in naive and COVID-19 recovered individuals.

The rapid development of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the design of accelerated vaccination schedules that have been extremely effective in naive individuals. While a two-dose immunization regimen with the BNT162b2 vaccine has been demonstrated to provide a 95% efficacy in naive individuals, the effects of the second vaccine dose in individuals who have previously recovered from natural SARS-CoV-2 infection has not been investigated in detail. In this study, we characterize SARS-CoV-2 spike-specific humoral and cellular immunity in naive and previously infected individuals during and after two doses of BNT162b2 vaccination. Our results demonstrate that, while the second dose increases both the humoral and cellular immunity in naive individuals, COVID-19 recovered individuals reach their peak of immunity after the first dose. These results suggests that a second dose, according to the current standard regimen of vaccination, may be not necessary in individuals previously infected with SARS-CoV-2.

CD4+ICOS+ T lymphocytes inhibit T cell activation 'in vitro' and attenuate autoimmune encephalitis 'in vivo'.

The inducible co-stimulator (ICOS, CD278) is essential to the efficient development of normal and pathological immune reactions. Since ICOS-deficient mice have enhanced susceptibility to experimental allergic encephalomyelitis (EAE), we have functionally analyzed a CD4+ICOS+ population comprising 6-15% of all CD4+ T cells in secondary lymphoid organs of unmanipulated wild-type mice and checked for their ability to suppress EAE. In C57BL/6 mice, CD4+ICOS+ cells were a major source of cytokines including IFN-gamma, IL-2, IL-4, IL-10 or IL-17A. Upon activation, these cells showed preferentially enhanced production of IL-4 or IL-10 but inhibited IFN-gamma production. In contrast, CD4+ICOS- cells mainly produced IFN-gamma. Interestingly, CD4+ICOS+ cells partially suppressed the proliferation of CD4+ICOS- or CD4+CD25- lymphocytes 'in vitro' by an IL-10-dependent mechanism. Furthermore, CD4+ICOS+ activated and expanded under appropriate conditions yielded a population enriched in cells producing IL-10 and T(h)2 cytokines that also suppressed the proliferation of CD4+CD25- lymphocytes. CD4+ICOS+ cells, before or after expansion in vitro, reduced the severity of EAE when transferred to ICOS-deficient mice. In the same EAE model, lymph node cells from ICOS-deficient mice receiving ICOS+ cells showed reduced IL-17A production and enhanced IL-10 secretion upon antigen activation in vitro. Thus, naturally occurring CD4+ICOS+ cells, expanded or not in vitro, are functionally relevant cells able of protecting ICOS-deficient mice from severe EAE.

ICOS deficiency hampers the homeostasis, development and function of NK cells.

Signaling through the inducible costimulator ICOS is required for the homeostasis and function of various immune cell populations, with an outstanding role in the generation and maintenance of germinal centers. Very recently, it has been suggested that the clinical phenotype of ICOS-deficient patients is much broader than initially anticipated and the innate immune response might be also affected. However, the role of the ICOS/ICOS-Ligand axis in the homeostasis and development of innate NK cells is not known, and reports on its participation in NK cell activation are scarce. NK cells may express low levels of ICOS that are markedly enhanced upon activation. We show here that ICOS-deficient (ICOS-KO) mice present low NK cell numbers and defects in the homeostasis of these cells, with delayed maturation and altered expression of the developmental NK cell markers CD122, NK1.1, CD11b or CD27. Our experiments in mixed bone marrow chimera mice indicate that, both, cell-intrinsic defects of ICOS-KO NK and deficiencies in the milieu of these mice contribute to the altered phenotype. ICOS-deficient NK cells show impaired production of IFN-γ and cytotoxicity, and a final outcome of defects in NK cell-mediated effector function during the response to poly(I:C) or vaccinia virus infection in vivo. Interestingly, we show that murine innate cells like IL-2-cultured NK and bone marrow-derived dendritic cells can simultaneously express ICOS and ICOS-Ligand; both molecules are functional in NK intracellular signaling, enhancing early phosphorylation of Akt and Erk, or IFN-γ secretion in IL-2-activated NK cells. Our study shows the functional importance of the ICOS/ICOS-L pair in NK cell homeostasis, differentiation and activity and suggests novel therapeutic targets for NK manipulation.

T-Cell-Specific Loss of the PI-3-Kinase p110α Catalytic Subunit Results in Enhanced Cytokine Production and Antitumor Response.

Class IA phosphatidylinositol 3-kinase (PI3K) catalytic subunits p110α and p110δ are targets in cancer therapy expressed at high levels in T lymphocytes. The role of p110δ PI3K in normal or pathological immune responses is well established, yet the importance of p110α subunits in T cell-dependent immune responses is not clear. To address this problem, mice with p110α conditionally deleted in CD4+ and CD8+ T lymphocytes (p110α-/-ΔT) were used. p110α-/-ΔT mice show normal development of T cell subsets, but slightly reduced numbers of CD4+ T cells in the spleen. "In vitro," TCR/CD3 plus CD28 activation of naive CD4+ and CD8+ p110α-/-ΔT T cells showed enhanced effector function, particularly IFN-γ secretion, T-bet induction, and Akt, Erk, or P38 activation. Tfh derived from p110α-/-ΔT cells also have enhanced responses when compared to normal mice, and IL-2 expanded p110α-/-ΔT CD8+ T cells had enhanced levels of LAMP-1 and Granzyme B. By contrast, the expansion of p110α-/-ΔT iTreg cells was diminished. Also, p110α-/-ΔT mice had enhanced anti-keyhole limpet hemocyanin (KLH) IFN-γ, or IL-4 responses and IgG1 and IgG2b anti-KLH antibodies, using CFA or Alum as adjuvant, respectively. When compared to WT mice, p110α-/-ΔT mice inoculated with B16.F10 melanoma showed delayed tumor progression. The percentage of CD8+ T lymphocytes was higher and the percentage of Treg cells lower in the spleen of tumor-bearing p110α-/-ΔT mice. Also, IFN-γ production in tumor antigen-activated spleen cells was enhanced. Thus, PI3K p110α plays a significant role in antigen activation and differentiation of CD4+ and CD8+ T lymphocytes modulating antitumor immunity.

Two Different Populations within the Healthy Elderly: Lack of Conflict Detection in Those at Risk of Cognitive Decline.

During healthy aging, inhibitory processing is affected at the sensorial, perceptual, and cognitive levels. The assessment of event-related potentials (ERPs) during the Stroop task has been used to study age-related decline in the efficiency of inhibitory processes. Studies using ERPs have found that the P300 amplitude increases and the N500 amplitude is attenuated in healthy elderly adults compared to those in young adults. On the other hand, it has been reported that theta excess in resting EEG with eyes closed is a good predictor of cognitive decline during aging 7 years later, while a normal EEG increases the probability of not developing cognitive decline. The behavioral and ERP responses during a Counting-Stroop task were compared between 22 healthy elderly subjects with normal EEG (Normal-EEG group) and 22 healthy elderly subjects with an excess of EEG theta activity (Theta-EEG group). Behaviorally, the Normal-EEG group showed a higher behavioral interference effect than the Theta-EEG group. ERP patterns were different between the groups, and two facts are highlighted: (a) the P300 amplitude was higher in the Theta-EEG group, with both groups showing a P300 effect in almost all electrodes, and (b) the Theta-EEG group did not show an N500 effect. These results suggest that the diminishment in inhibitory control observed in the Theta-EEG group may be compensated by different processes in earlier stages, which would allow them to perform the task with similar efficiency to that of participants with a normal EEG. This study is the first to show that healthy elderly subjects with an excess of theta EEG activity not only are at risk of developing cognitive decline but already have a cognitive impairment.

Improving the efficiency of Auditory Brainstem Responses in newborns, using a 60clicks/s stimulation rate.

Recent evidence suggests that Auditory Brainstem Responses (ABR), in neonates with risk factors for neurological damage, may show auditory brainstem abnormalities, even in patients with normal hearing. To compare the recording and diagnostic accuracy of neonatal Auditory Brainstem Responses (ABR), using 10 and 60clicks/s stimulation rates, two groups of neonates were prospectively studied: 30 healthy full-term neonates, with no peri- or postnatal complications; and 30 high-risk newborns with two or more of the following conditions: hyperbilirubinemia, use of ototoxic drugs, birth weight inferior to 1500g, perinatal sepsis, intraventricular hemorrhage, and/or mechanical ventilation. Correlation between ABR trials, recording duration, and the absolute and interpeak latencies of ABR waves I, III and V, were measured. ROC-curve analysis assessed the diagnostic accuracy of both stimulation rates. The correlations between ABRs trials were significantly higher at 60clicks/s than at 10clicks/s (F(1,116)=14.5, p<0.0002). Recording duration at 60clicks/s was significantly lower (t=20.9, p<0.0001). ROC-curve comparisons showed increased diagnostic accuracy at the stimulation rate of 60clicks/s, for waves I (D=2.04, p=0.04), V (D=2.02, p=0.04), interpeak latencies III-V (D=2.2, p=0.02), and I-V (D=2.86, p=0.004). In neonates, the use of 60clicks/s stimulation rate permits a substantial shortening of the ABR recording, with greater diagnostic accuracy and replicability.