Cutaneous lesions as a clue to severe combined immunodeficiency.

A 2-month-old boy experienced cutaneous lesions that revealed an underlying severe, combined immunodeficiency (SCID). It is important to recognize cutaneous manifestations of primary immunodeficiency disorders, as they may provide the earliest clue to a defect in immune function.

A novel syndrome of severe neutrophil dysfunction: unresponsiveness confined to chemotaxin-induced functions.

We have identified a patient with a number of neutrophil dysfunctions. The patient was a female baby who lived for 8 months. During her life, she developed severe bacterial infections and showed omphalitis, impaired wound healing, and a pronounced leukocytosis. She was not a patient with leukocyte adhesion deficiency, because all leukocyte CD18 complex proteins were expressed at normal levels. Yet, neutrophil polarization and chemotaxis to platelet-activating factor, leukotriene B4, or formyl-methionyl-leucyl-phenylalanine (FMLP) were completely absent. We found a strong defect in actin polymerization in response to chemotactic stimuli, but only a retarded or even normal reaction with other stimuli. This indicates that the cellular dysfunctions were not due to an intrinsic defect in actin metabolism. Instead, the regulation of actin polymerization with chemotactic stimuli seemed to be defective. We concentrated on FMLP-induced responses in the patient's neutrophils. Functions dependent on activation of complement receptor type 3, such as aggregation or adherence to endothelial cells, were normally induced. Binding to serum-coated coverslips was normal in cell number; however, spreading was not observed. Exocytosis from the specific granules was readily induced. In contrast, FMLP failed to induce a respiratory burst activity or degranulation of the azurophil granules. FMLP induced a normal increase in free intracellular Ca2+, but a decreased formation of diglycerides (especially the 1-O-alkyl,2-acyl compounds). Thus, we have described a patient whose neutrophils show a severe defect in functional activation via chemotaxin receptors, resulting in a selective absence of NADPH oxidase activity, exocytosis from the azurophil granules, and actin polymerization. Our findings show that actin polymerization for neutrophil spreading and locomotion is regulated differently from that for phagocytosis. Also, the release of azurophil and specific granule contents is clearly shown to be regulated in a different way.

How common are common mental disorders? Evidence that lifetime prevalence rates are doubled by prospective versus retrospective ascertainment.

BACKGROUND: Most information about the lifetime prevalence of mental disorders comes from retrospective surveys, but how much these surveys have undercounted due to recall failure is unknown. We compared results from a prospective study with those from retrospective studies. METHOD: The representative 1972-1973 Dunedin New Zealand birth cohort (n=1037) was followed to age 32 years with 96% retention, and compared to the national New Zealand Mental Health Survey (NZMHS) and two US National Comorbidity Surveys (NCS and NCS-R). Measures were research diagnoses of anxiety, depression, alcohol dependence and cannabis dependence from ages 18 to 32 years. RESULTS: The prevalence of lifetime disorder to age 32 was approximately doubled in prospective as compared to retrospective data for all four disorder types. Moreover, across disorders, prospective measurement yielded a mean past-year-to-lifetime ratio of 38% whereas retrospective measurement yielded higher mean past-year-to-lifetime ratios of 57% (NZMHS, NCS-R) and 65% (NCS). CONCLUSIONS: Prospective longitudinal studies complement retrospective surveys by providing unique information about lifetime prevalence. The experience of at least one episode of DSM-defined disorder during a lifetime may be far more common in the population than previously thought. Research should ask what this means for etiological theory, construct validity of the DSM approach, public perception of stigma, estimates of the burden of disease and public health policy.

Safety profile of L-arginine infusion in moderately severe falciparum malaria.

BACKGROUND: L-arginine infusion improves endothelial function in malaria but its safety profile has not been described in detail. We assessed clinical symptoms, hemodynamic status and biochemical parameters before and after a single L-arginine infusion in adults with moderately severe malaria. METHODOLOGY AND FINDINGS: In an ascending dose study, adjunctive intravenous L-arginine hydrochloride was infused over 30 minutes in doses of 3 g, 6 g and 12 g to three separate groups of 10 adults hospitalized with moderately severe Plasmodium falciparum malaria in addition to standard quinine therapy. Symptoms, vital signs and selected biochemical measurements were assessed before, during, and for 24 hours after infusion. No new or worsening symptoms developed apart from mild discomfort at the intravenous cannula site in two patients. There was a dose-response relationship between increasing mg/kg dose and the maximum decrease in systolic (rho = 0.463; Spearman's, p = 0.02) and diastolic blood pressure (r = 0.42; Pearson's, p = 0.02), and with the maximum increment in blood potassium (r = 0.70, p<0.001) and maximum decrement in bicarbonate concentrations (r = 0.53, p = 0.003) and pH (r = 0.48, p = 0.007). At the highest dose (12 g), changes in blood pressure and electrolytes were not clinically significant, with a mean maximum decrease in mean arterial blood pressure of 6 mmHg (range: 0-11; p<0.001), mean maximal increase in potassium of 0.5 mmol/L (range 0.2-0.7 mmol/L; p<0.001), and mean maximal decrease in bicarbonate of 3 mEq/L (range 1-7; p<0.01) without a significant change in pH. There was no significant dose-response relationship with blood phosphate, lactate, anion gap and glucose concentrations. All patients had an uncomplicated clinical recovery. CONCLUSIONS/SIGNIFICANCE: Infusion of up to 12 g of intravenous L-arginine hydrochloride over 30 minutes is well tolerated in adults with moderately severe malaria, with no clinically important changes in hemodynamic or biochemical status. Trials of adjunctive L-arginine can be extended to phase 2 studies in severe malaria. TRIAL REGISTRATION: ClinicalTrials.gov NCT00147368.

Analysis of the effect of yoga on selective attention and mental concentration in young adults

Gemstone Team Om

Cardiac beta ARK1 inhibition prolongs survival and augments beta blocker therapy in a mouse model of severe heart failure.

Chronic human heart failure is characterized by abnormalities in beta-adrenergic receptor (betaAR) signaling, including increased levels of betaAR kinase 1 (betaARK1), which seems critical to the pathogenesis of the disease. To determine whether inhibition of betaARK1 is sufficient to rescue a model of severe heart failure, we mated transgenic mice overexpressing a peptide inhibitor of betaARK1 (betaARKct) with transgenic mice overexpressing the sarcoplasmic reticulum Ca(2+)-binding protein, calsequestrin (CSQ). CSQ mice have a severe cardiomyopathy and markedly shortened survival (9 +/- 1 weeks). In contrast, CSQ/betaARKct mice exhibited a significant increase in mean survival age (15 +/- 1 weeks; P < 0.0001) and showed less cardiac dilation, and cardiac function was significantly improved (CSQ vs. CSQ/betaARKct, left ventricular end diastolic dimension 5.60 +/- 0.17 mm vs. 4.19 +/- 0.09 mm, P < 0.005; % fractional shortening, 15 +/- 2 vs. 36 +/- 2, P < 0.005). The enhancement of the survival rate in CSQ/betaARKct mice was substantially potentiated by chronic treatment with the betaAR antagonist metoprolol (CSQ/betaARKct nontreated vs. CSQ/betaARKct metoprolol treated, 15 +/- 1 weeks vs. 25 +/- 2 weeks, P < 0.0001). Thus, overexpression of the betaARKct resulted in a marked prolongation in survival and improved cardiac function in a mouse model of severe cardiomyopathy that can be potentiated with beta-blocker therapy. These data demonstrate a significant synergy between an established heart-failure treatment and the strategy of betaARK1 inhibition.

Mental hoop diaries: emotional memories of a college basketball game in rival fans.

The rivalry between the men's basketball teams of Duke University and the University of North Carolina-Chapel Hill (UNC) is one of the most storied traditions in college sports. A subculture of students at each university form social bonds with fellow fans, develop expertise in college basketball rules, team statistics, and individual players, and self-identify as a member of a fan group. The present study capitalized on the high personal investment of these fans and the strong affective tenor of a Duke-UNC basketball game to examine the neural correlates of emotional memory retrieval for a complex sporting event. Male fans watched a competitive, archived game in a social setting. During a subsequent functional magnetic resonance imaging session, participants viewed video clips depicting individual plays of the game that ended with the ball being released toward the basket. For each play, participants recalled whether or not the shot went into the basket. Hemodynamic signal changes time locked to correct memory decisions were analyzed as a function of emotional intensity and valence, according to the fan's perspective. Results showed intensity-modulated retrieval activity in midline cortical structures, sensorimotor cortex, the striatum, and the medial temporal lobe, including the amygdala. Positively valent memories specifically recruited processing in dorsal frontoparietal regions, and additional activity in the insula and medial temporal lobe for positively valent shots recalled with high confidence. This novel paradigm reveals how brain regions implicated in emotion, memory retrieval, visuomotor imagery, and social cognition contribute to the recollection of specific plays in the mind of a sports fan.

When Working Memory and Attention Compete: Characterizing the Dynamic Interdependence between our Mental Workspace and External Environment

All of us are taxed with juggling our inner mental lives with immediate external task demands. For many years, the temporary maintenance of internal information was considered to be handled by a dedicated working memory (WM) system. It has recently become increasingly clear, however, that such short-term internal activation interacts with attention focused on external stimuli. It is unclear, however, exactly why these two interact, at what level of processing, and to what degree. Because our internal maintenance and external attention processes co-occur with one another, the manner of their interaction has vast implications for functioning in daily life. The work described here has employed original experimental paradigms combining WM and attention task elements, functional magnetic resonance imaging (fMRI) to illuminate the associated neural processes, and transcranial magnetic stimulation (TMS) to clarify the causal substrates of attentional brain function. These studies have examined a mechanism that might explain why (and when) the content of WM can involuntarily capture visual attention. They have, furthermore, tested whether fundamental attentional selection processes operate within WM, and whether they are reciprocal with attention. Finally, they have illuminated the neural consequences of competing attentional demands. The findings indicate that WM shares representations, operating principles, and cognitive resources with externally-oriented attention.

Improving mental health among people living with HIV: a review of intervention trials in low- and middle-income countries.

People living with HIV (PLWH) experience greater psychological distress than the general population. Evidence from high-incomes countries suggests that psychological interventions for PLWH can improve mental health symptoms, quality of life, and HIV care engagement. However, little is known about the effectiveness of mental health interventions for PLWH in low and middle-income countries (LMICs), where the large majority of PLWH reside. This systematized review aims to synthesize findings from mental health intervention trials with PLWH in LMICs to inform the delivery of mental health services in these settings. A systematic search strategy was undertaken to identify peer-reviewed published papers of intervention trials addressing negative psychological states or disorders (e.g., depression, anxiety) among PLWH in LMIC settings. Search results were assessed against pre-established inclusion and exclusion criteria. Data from papers meeting criteria were extracted for synthesis. Twenty-six papers, published between 2000 and 2014, describing 22 unique interventions were identified. Trials were implemented in sub-Saharan Africa (n=13), Asia (n=7), and the Middle East (n=2), and addressed mental health using a variety of approaches, including cognitive-behavioral (n=18), family-level (n=2), and pharmacological (n=2) treatments. Four randomized controlled trials reported significant intervention effects in mental health outcomes, and eleven preliminary studies demonstrated promising findings. Among the limited mental health intervention trials with PLWH in LMICs, few demonstrated efficacy. Mental health interventions for PLWH in LMICs must be further developed and adapted for resource-limited settings to improve effectiveness.

Accuracy of proactive case finding for mental disorders by community informants in Nepal.

BACKGROUND: Accurate detection of persons in need of mental healthcare is crucial to reduce the treatment gap between psychiatric burden and service use in low- and middle-income (LAMI) countries. AIMS: To evaluate the accuracy of a community-based proactive case-finding strategy (Community Informant Detection Tool, CIDT), involving pictorial vignettes, designed to initiate pathways for mental health treatment in primary care settings. METHOD: Community informants using the CIDT identified screen positive (n = 110) and negative persons (n = 85). Participants were then administered the Composite International Diagnostic Interview (CIDI). RESULTS: The CIDT has a positive predictive value of 0.64 (0.68 for adults only) and a negative predictive value of 0.93 (0.91 for adults only). CONCLUSIONS: The CIDT has promising detection properties for psychiatric caseness. Further research should investigate its potential to increase demand for, and access to, mental health services.

An unusual case of severe combined immunodeficiency with hypereosinophilia

SCOPUS: ar.j

Adaptación curricular para el área de matemática: dificultades cognitivas (síndrome de Down con retraso mental leve)

Este trabajo incluye una propuesta de adaptación curricular para un alumno/a de 3ºESO para el área de matemáticas.Como en toda adpatación curricular, se proponen recursos,medidas metodológicas, contenidos, objetivos, criterios de evaluación para permitir el acceso al currículo a dicho alumno.

Tuxmath: un juego para el cálculo mental

Con este número, estrenamos MatemásTIC. Aunque el nombre ya deja entrever lo que pueden ser los contenidos que podemos encontrar, por la amplia variedad de los mismos, nos hemos marcado unos objetivos claros que nos sirvan de referencia para la estructura, temas y forma en la que se van a tratar.