Prophet In His Own Country: Carlos Chagas And The Nobel Prize.

In 1909, Carlos Chagas (1878-1934) discovered a new protozoon, Trypanosoma cruzi, and the (previously unknown) disease that it causes. Within a few months, virtually single-handed, he described the pathogen, its vector, and the clinical features of American trypanosomiasis (Chagas disease), a feat unique in medical history. He headed the Oswaldo Cruz Institute after the death of its founder (1917) until his own death; and from 1920 until 1926 he also directed the Brazilian Department of Public Health. His discovery brought him worldwide acclaim, but at home antagonism against Chagas, muted for years, finally flared up in a campaign that was acted out in the 1921-22 plenary sessions of the National Academy of Medicine. Chagas's name was repeatedly proposed for the Nobel Prize but he never received it; this hostile campaign may have been instrumental in costing him the award.46453254

Comorbidity Between Major Depression and Alcohol Use Disorder From Adolescence to Adulthood

Background—Limited information exists regarding the long-term development of comorbidity between Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD; abuse/dependence). Using a representative prospective study, we examine multiple aspects pertaining to MDD+AUD comorbidity, with a focus on the relation between disorders across periods (adolescence, early adulthood, adulthood) and cumulative impairments by age 30. Method—816 participants were diagnostically interviewed at ages 16, 17, 24, and 30. Results—Rates of comorbid MDD+AUD were low in adolescence (2%), but increased in early adulthood (10%) and adulthood (7%). Rates of cumulative comorbidity were elevated (21%). Most individuals with a history of MDD or AUD had the other disorder, except for women with MDD. Prospectively, adolescent AUD predicted early adult MDD, while early adult MDD predicted adult AUD. Compared to pure disorders, MDD+AUD was associated with higher risk of alcohol dependence, suicide attempt, lower global functioning, and life dissatisfaction. Conclusions—Lifetime rates of comorbid MDD+AUD were considerably higher than in crosssectional studies. Comorbidity was partly explained by bidirectional and developmentally-specific associations and predicted selected rather than generalized impairments. Clinically, our findings emphasize the need to always carefully assess comorbidity in patients with MDD or AUD, taking into account concurrency and developmental timing

Adolescent suicide attempts and adult adjustment

Background: Adolescent suicide attempts are disproportionally prevalent and frequently of low severity, raising questions regarding their long-term prognostic implications. In this study, we examined whether adolescent attempts were asso- ciated with impairments related to suicidality, psychopathology, and psychosocial functioning in adulthood (objective 1) and whether these impairments were better accounted for by concurrent adolescent confounders (objective 2). Method: Eight hundred and sixteen adolescents were assessed using interviews and question- naires at four time points from adolescence to adulthood. We examined whether lifetime suicide attempts in adolescence (by T2, mean age 17) predicted adult out- comes (by T4, mean age 30) using linear and logistic regressions in unadjusted models (objective 1) and adjusting for sociodemographic background, adolescent psychopathology, and family risk factors (objective 2). Results: In unadjusted analyses, adolescent suicide attempts predicted poorer adjustment on all outcomes, except those related to social role status. After adjustment, adolescent attempts remained predictive of axis I and II psychopathology (anxiety disorder, antisocial and borderline personality disorder symptoms), global and social adjustment, risky sex, and psychiatric treatment utilization. However, adolescent attempts no longer predicted most adult outcomes, notably suicide attempts and major depressive disorder. Secondary analyses indicated that associations did not differ by sex and attempt characteristics (intent, lethality, recurrence). Conclusions: Adolescent suicide attempters are at high risk of protracted and wide-ranging im- pairments, regardless of the characteristics of their attempt. Although attempts specifically predict (and possibly influence) several outcomes, results suggest that most impairments reflect the confounding contributions of other individual and family problems or vulnerabilites in adolescent attempters

The Mycobacterium tuberculosis Phagosome Is a HLA-I Processing Competent Organelle

Mycobacterium tuberculosis (Mtb) resides in a long-lived phagosomal compartment that resists maturation. The manner by which Mtb antigens are processed and presented on MHC Class I molecules is poorly understood. Using human dendritic cells and IFN-γ release by CD8+ T cell clones, we examined the processing and presentation pathway for two Mtb–derived antigens, each presented by a distinct HLA-I allele (HLA-Ia versus HLA-Ib). Presentation of both antigens is blocked by the retrotranslocation inhibitor exotoxin A. Inhibitor studies demonstrate that, after reaching the cytosol, both antigens require proteasomal degradation and TAP transport, but differ in the requirement for ER–golgi egress and new protein synthesis. Specifically, presentation by HLA-B8 but not HLA-E requires newly synthesized HLA-I and transport through the ER–golgi. Phenotypic analysis of the Mtb phagosome by flow organellometry revealed the presence of Class I and loading accessory molecules, including TAP and PDI. Furthermore, loaded HLA-I:peptide complexes are present within the Mtb phagosome, with a pronounced bias towards HLA-E:peptide complexes. In addition, protein analysis also reveals that HLA-E is enriched within the Mtb phagosome compared to HLA-A2. Together, these data suggest that the phagosome, through acquisition of ER–localized machinery and as a site of HLA-I loading, plays a vital role in the presentation of Mtb–derived antigens, similar to that described for presentation of latex bead-associated antigens. This is, to our knowledge, the first description of this presentation pathway for an intracellular pathogen. Moreover, these data suggest that HLA-E may play a unique role in the presentation of phagosomal antigens

Brief behavioural activation for adolescent depression: working with complexity and risk

Given the long-term negative outcomes associated with depression in adolescence, there is a pressing need to develop brief, evidence based treatments that are accessible to more young people experiencing low mood. Behavioural Activation (BA) is an effective treatment for adult depression, however little research has focused on the use of BA with depressed adolescents, particularly with briefer forms of BA. In this article we outline an adaptation of brief Behavioral Activation Treatment of Depression (BATD) designed for adolescents and delivered in eight sessions (Brief BA). This case example illustrates how a structured, brief intervention was useful for a depressed young person with a number of complicating and risk factors

Endogenous human cytomegalovirus gB is presented efficiently by MHC class II molecules to CD4+ CTL

Human cytomegalovirus (HCMV) infects endothelial, epithelial, and glial cells in vivo. These cells can express MHC class II proteins, but are unlikely to play important roles in priming host immunity. Instead, it seems that class II presentation of endogenous HCMV antigens in these cells allows recognition of virus infection. We characterized class II presentation of HCMV glycoprotein B (gB), a membrane protein that accumulates extensively in endosomes during virus assembly. Human CD4+ T cells specific for gB were both highly abundant in blood and cytolytic in vivo. gB-specific CD4+ T cell clones recognized gB that was expressed in glial, endothelial, and epithelial cells, but not exogenous gB that was fed to these cells. Glial cells efficiently presented extremely low levels of endogenous gB—expressed by adenovirus vectors or after HCMV infection—and stimulated CD4+ T cells better than DCs that were incubated with exogenous gB. Presentation of endogenous gB required sorting of gB to endosomal compartments and processing by acidic proteases. Although presentation of cellular proteins that traffic into endosomes is well known, our observations demonstrate for the first time that a viral protein sorted to endosomes is presented exceptionally well, and can promote CD4+ T cell recognition and killing of biologically important host cells