Design and Characterization of a Multistage Peptide-Based Vaccine Platform to Target Mycobacterium tuberculosis Infection.

The complex immunopathology ofMycobacterium tuberculosis(Mtb) is one of the main challenges in developing a novel vaccine against this pathogen, particularly regarding eliciting protection against both active and latent stages. Multistage vaccines, which contain antigens expressed in both phases, represent a promising strategy for addressing this issue, as testified by the tuberculosis vaccine clinical pipeline. Given this approach, we designed and characterized a multistage peptide-based vaccine platform containing CD4+ and CD8+ T cell epitopes previously validated for inducing a relevant T cell response against Mtb. After preliminary screening, CFP10 (32-39), GlfT2 (4-12), HBHA (185-194), and PPE15 (1-15) were selected as promising candidates, and we proved that the PM1 pool of these peptides triggered a T cell response in Mtb-sensitized human peripheral blood mononuclear cells (PBMCs). Taking advantage of the use of thiol-maleimide chemoselective ligation, we synthesized a multiepitope conjugate (Ac-CGHP). Our results showed a structure-activity relationship between the conjugation and a higher tendency to fold and assume an ordered secondary structure. Moreover, the palmitoylated conjugate (Pal-CGHP) comprising the same peptide antigens was associated with an enhanced cellular uptake in human and murine antigen-presenting cells and a better immunogenicity profile. Immunization study, conducted in BALB/c mice, showed that Pal-CGHP induced a significantly higher T cell proliferation and production of IFNγ and TNFα over PM1 formulated in the Sigma Adjuvant System.

Novel Polycondensed Partly Saturated ß-Carbolines Including Ferrocene Derivatives: Synthesis, DFT-Supported Structural Analysis, Mechanism of Some Diastereoselective Transformations and a Preliminary Study of Their in vitro Antiproliferative Effects.

Use of a Pictet-Spengler reaction of tryptamine and l-tryptophan methyl ester and subsequent reduction of the nitro group followed by further cyclocondensation with aryl aldehydes and formyl-substituted carboxylic acids, including ferrocene-based components, furnished a series of diastereomeric 6-aryl-substituted 5,6,8,9,14,14b-hexahydroindolo[2',3':3,4]pyrido[1-c]-quinazolines and 5,5b,17,18-tetrahydroindolo[2',3':3,4]pyrido[1,2-c]isoindolo[2,1-a]quinazolin-11-(15bH)-ones with the elements of central-, planar and conformational chirality. The relative configuration and the conformations of the novel polycyclic indole derivatives were determined by 1H- and 13C-NMR methods supplemented by comparative DFT analysis of the possible diastereomers. The structure of one of the pentacyclic methyl esters with defined absolute configuration "S" was also confirmed by single crystal X-ray diffraction measurement. Accounting for the characteristic substituent-dependent diastereoselective formation of the products multistep mechanisms were proposed on the basis of the results of DFT modeling. Preliminary in vitro cytotoxic assays of the products revealed moderate-to-significant antiproliferative effects against PANC-1-, COLO-205-, A-2058 and EBC-1 cell lines that proved to be highly dependent on the stereostructure and on the substitution pattern of the pending aryl substituent.

Are Children or Adolescents More at Risk for Posttraumatic Stress Reactions Following Exposure to Violence?: Evidence From Post-Genocide Rwanda.

Whether children or adolescents exhibit higher levels of posttraumatic stress symptoms (PTSS) in response to violence is an unresolved research question. We examine this issue in UNICEF's 1995 National Trauma Survey (NTS) of 8-19-year-olds (n = 942) who survived the Rwandan Genocide and lived and attended schools in the community. PTSS were assessed with a symptom checklist based on DSM-IV indexed using an overall score comprising the sum of scores on all items and mean item scores of each of five distinct factors identified in a factor analysis within this sample. Eighty percent of the sample had witnessed massacres; 25%, rape/sexual mutilation. The overall symptom score among children was significantly (p < 0.05) lower than among adolescents. Among the five separate factors, this direct association of age with symptom levels held for two: re-experiencing (p < 0.001) and dysphoric arousal (p < 0.05), but not for the remaining three: avoidance, numbing, and anxious arousal. This discordance in factorial response to violence may help explain prevailing inconsistencies in the age-PTSS association reported to date.

Protection by humoral elements independent of virus neutralization activity against an influenza virus challenge.

To investigate the protective efficacy of a seasonal trivalent inactivated whole virion influenza vaccine (TIV) adjuvanted with aluminum phosphate (Fluval AB, referred to here as TIV+Al), we immunized mice with the TIV+Al, and as controls, with TIV, TIV+Al combined with Freund adjuvant (TIV+Al+F), inactivated A/PR/8/34(H1N1) (PR8) strain or PBS, and challenged them with a lethal dose of a mouse-adapted PR8 virus. Serum pools from immunized mice were passively transferred to recipient mice that were then challenged similarly. All actively immunized mice survived the challenge. Of recipient mice receiving serum from mice actively immunized with TIV, TIV+Al or TIV+Al+F, 20%, 80%, and 100% survived, respectively. Rates of mortality and morbidity of recipient mice were inversely proportional to the hemagglutination inhibition (HI) antibody level to the vaccine virus in the absence of detectable PR8-specific HI, neuraminidase inhibition (NI) and virus neutralization (VN) antibodies. No cross-reactivity was observed between vaccine and PR8 strains in in vitro HI, NI or VN assays. In splenocytes from TIV+Al-immunized mice production of IFN-γ or granzyme-B protein and mRNA expression increased (p<0.05). Thus, antibodies play a major role in the protection against a mismatched challenge infection independent of HI, NI and VN activity, but cellular immune responses may contribute to full protection in actively immunized mice.

[Psychological interventions following trauma to prevent posttraumatic stress disorder. A systematic review of the literature]. / Pszichológiai intervenciók traumatikus események után a poszttraumás stressz zavar megelozésére. Szisztematikus irodalmi áttekintés.

INTRODUCTION: Because of the high prevalence of exposure to traumatic events and its negative consequences on mental health, the importance of effective interventions to prevent posttraumatic stress disorder has been emphasized. AIM: The authors wanted to evaluate the current status of evidence regarding early psychological interventions after traumatization. METHOD: A search was conducted in ProQuest PILOTS, PubMed, and Web of Science for early psychological interventions that were published between 2005 and 2015. RESULTS: Twenty-one trials were identified, of which 6 presented immediate interventions (within 72 hours) and the rest early interventions within the first month. Based on these research findings immediate interventions are not effective, whilst multi-session cognitive behavior therapies could be effective in symptom reduction. CONCLUSIONS: Multi-session cognitive behavior therapy is preferred over immediate one session interventions especially over debriefing. A natural decline of symptoms was observed among controls and, therefore, targeted interventions are recommended only for people with higher risk for developing subsequent posttraumatic stress disorder.

Nanoparticle encapsulated lipopeptide conjugate of antitubercular drug isoniazid: in vitro intracellular activity and in vivo efficacy in a Guinea pig model of tuberculosis.

Considering that Mycobacterium tuberculosis (Mtb) can survive in host phagocytes for decades and currently applied drugs are largely ineffective in killing intracellular Mtb, novel targeted delivery approaches to improve tuberculosis chemotherapy are urgently needed. In order to enhance the efficacy of a clinically used antitubercular agent (isoniazid, INH) a novel lipopeptide carrier was designed based on the sequence of tuftsin, which has been reported as a macrophage-targeting molecule. The conjugate showed relevant in vitro activity on Mtb H37Rv culture with low cytotoxicity and hemolytic activity on human cells. The conjugate directly killed intracellular Mtb and shows much greater efficacy than free INH. To improve bioavailability, the conjugate was encapsulated into poly(lactide-co-glycolide) (PLGA) nanoparticles and tested in vivo in a guinea pig infection model. External clinical signs, detectable mycobacterial colonies in the organs, and the histopathological findings substantiate the potent chemotherapeutic effect of orally administered conjugate-loaded nanoparticles.

[From life events to symptoms of anxiety and depression: the role of dysfunctional attitudes and coping]. / Az életeseményektol a depressziós és szorongásos panaszokig: a diszfunkcionális attitudök és a megküzdés szerepe a patogenezis folyamatában.

UNLABELLED: The aim of the present study was a systematic path-analytical investigation between the effects of life events, dysfunctional attitudes and coping strategies in relation with the exhibited depressive and anxiety symptoms in patients with mental disorders. METHODS: Self-report data of 234 patients from our outpatient psychotherapy unit were analyzed. Life events, dysfunctional attitudes, coping strategies as well as symptoms of anxiety and depression were assessed by self-administerd questionnaires. Statistical methods included structural equation modelling, which enables the estimation of the magnitude and strength of individual variables within an overarching casual model, thus yielding a complex view on the possible processes underlying the development of the clinical symptoms of anxiety and depression. RESULTS: Our findings indicate that both the number of negative life events and their subjectively experienced intensity contributed to the increase of dysfunctional attitudes. The presence of dysfunctional attitudes decreased the use of problem-focused coping strategies and increased the use of emotion-focused coping strategies. The use of problem-focused coping decreased symptom occurrence and emotion-focused coping strategies increased the frequency of symptoms of anxiety and depression. Our findings suggest that dysfunctional need for achievement and perfectionism directly increase the probability of depressive symptom manifestation. The attitude of external locus of control showed a significant relationship with anxiety symptoms through emotion-focused coping strategies and directly as well. CONCLUSION: Restructuring dysfunctional attitudes and developing problem-focused coping strategies are an important part of psychotherapeutic interventions aiming to decrease anxiety and depressive symptoms.

Cellular Immunity of Drosophila willistoni Reveals Novel Complexity in Insect Anti-Parasitoid Defense.

Coevolution of hosts and their parasites has shaped heterogeneity of effector hemocyte types, providing immune defense reactions with variable effectiveness. In this work, we characterize hemocytes of Drosophila willistoni, a species that has evolved a cellular immune system with extensive variation and a high degree of plasticity. Monoclonal antibodies were raised and used in indirect immunofluorescence experiments to characterize hemocyte subpopulations, follow their functional features and differentiation. Pagocytosis and parasitization assays were used to determine the functional characteristics of hemocyte types. Samples were visualized using confocal and epifluorescence microscopy. We identified a new multinucleated giant hemocyte (MGH) type, which differentiates in the course of the cellular immune response to parasitoids. These cells differentiate in the circulation through nuclear division and cell fusion, and can also be derived from the central hematopoietic organ, the lymph gland. They have a binary function as they take up bacteria by phagocytosis and are involved in the encapsulation and elimination of the parasitoid. Here, we show that, in response to large foreign particles, such as parasitoids, MGHs differentiate, have a binary function and contribute to a highly effective cellular immune response, similar to the foreign body giant cells of vertebrates.

Protection of Chinese painted quails (Coturnix chinensis) against a highly pathogenic H5N1 avian influenza virus strain after vaccination.

Chinese painted quails immunized with a single dose (6 µg HA) of inactivated H5N1 (clade 1) influenza vaccine NIBRG-14 and challenged with 100 LD50 of the heterologous A/Swan/Nagybaracska/01/06(H5N1) (clade 2.2) strain were protected, whereas unvaccinated quails died after challenge. No viral antigens or RNA were detected in cloacal swabs from immunized animals. Sera obtained post-immunization gave low titres in serological assays against the vaccine and the challenge viruses. Our results demonstrate the protective efficacy of the NIBRG-14 strain against the challenge virus and the usefulness of these small birds in protection studies of influenza vaccines.

First description of hypospadias and inguinal bilateral cryptorchidism in mouflon (Ovis Gmelini Musimon) - short communication.

A mouflon showing severe weight loss and cachexia was examined. The animal had horns and a male-like body frame but the preputial fur was missing. The scrotum was completely absent. Both testicles were located next to the inguinal canal under the skin, and appeared only slightly smaller than normal. The prepuce was located in a perianal position under the anus and it resembled a vulva. The penis was underdeveloped and curled up inside the prepuce like an enlarged clitoris. The bulbourethral region and the urinary bladder looked normal. The orifice of the urethra was located in its normal position, but the glans penis appeared deformed. Microscopic examination of the testicles revealed mild degeneration of the seminiferous tubules and a marked proliferation of the interstitial connective tissue with Leydig cells still present. There were no marked changes in the bulbar part of the penis but the apical part exhibited marked interstitial fibrosis. This is the first description of hypospadias and cryptorchidism in mouflon.

[Posttraumatic stress symptoms, dysfunctional attitudes and ways of coping in a clinical sample of PTSD patients]. / Poszttraumás stressztünetek, diszfunkcionalis attitudök és megküzdési módok -- egy klinikai minta explorativ vizsgálata.

INTRODUCTION: In the present study specific characteristics of PTSD patients were explored in a clinical sample with particular regard to dysfunctional attitudes and coping strategies. The purpose was to draw attention to this rarely investigated but presumably prevalent psychiatric disorder in the Hungarian population. METHOD: Twenty-two PTSD patients' retrospective data was analyzed who presented at our clinic for outpatient psychotherapy treatment. Patients were assessed on depressive, anxiety, hopelessness, and posttraumatic stress symptoms, as well as dysfunctional attitudes and coping strategies. RESULTS: Thirty-two percent (n=7) of the sample is male and 68% (n=15) is female, the mean age is 34.77 years. Based on trauma type 40.9% (n=9) had a motor vehicle accident, 18.2% (n=4) lost a close relative, 18.2% (n=4) was a victim of sexual or physical assault. There is great variance in the duration since the trauma (2 months to 10 years). The results suggest that posttraumatic stress symptoms (PTSSs) are associated with the dysfunctional attitudes of need for achievement and external control, and with avoidant and conforming coping styles. Additionally, PTSSs were highly comorbid with depressive and anxiety symptoms. CONCLUSION: The results imply that PTSD patients in Hungary have similar characteristics as international findings indicate.

Novel Assay Platform to Evaluate Intracellular Killing of Mycobacterium tuberculosis: In Vitro and In Vivo Validation.

One of the main hallmarks of tuberculosis (TB) is the ability of the causative agent to transform into a stage of dormancy and the capability of long persistence in the host phagocytes. It is believed that approximately one-third of the population of the world is latently infected with Mycobacterium tuberculosis (Mtb), and 5%-10% of these individuals can develop clinical manifestations of active TB even decades after the initial infection. In this latent, intracellular form, the bacillus is shielded by an extremely robust cell wall and becomes phenotypically resistant to most antituberculars. Therefore, there is a clear rationale to develop novel compounds or carrier-conjugated constructs of existing drugs that are effective against the intracellular form of the bacilli. In this paper, we describe an experimental road map to define optimal candidates against intracellular Mtb and potential compounds effective in the therapy of latent TB. To validate our approach, isoniazid, a first-line antitubercular drug was employed, which is active against extracellular Mtb in the submicromolar range, but ineffective against the intracellular form of the bacteria. Cationic peptide conjugates of isoniazid were synthesized and employed to study the host-directed drug delivery. To measure the intracellular killing activity of the compounds, Mtb-infected MonoMac-6 human monocytic cells were utilized. We have assessed the antitubercular activity, cytotoxicity, membrane interactions in combination with internalization efficacy, localization, and penetration ability on interface and tissue-mimicking 3D models. Based on these in vitro data, most active compounds were further evaluated in vivo in a murine model of TB. Intraperitoneal infectious route was employed to induce a course of slowly progressive and systemic disease. The well-being of the animals, monitored by the body weight, allows a prolonged experimental setup and provides a great opportunity to test the long-term activity of the drug candidates. Having shown the great potency of this simple and suitable experimental design for antimicrobial research, the proposed novel assay platform could be used in the future to develop further innovative and highly effective antituberculars.

A Convenient Synthetic Method to Improve Immunogenicity of Mycobacterium tuberculosis Related T-Cell Epitope Peptides.

Epitopes from different proteins expressed by Mycobacterium tuberculosis (Rv1886c, Rv0341, Rv3873) were selected based on previously reported antigenic properties. Relatively short linear T-cell epitope peptides generally have unordered structure, limited immunogenicity, and low in vivo stability. Therefore, they rely on proper formulation and on the addition of adjuvants. Here we report a convenient synthetic route to induce a more potent immune response by the formation of a trivalent conjugate in spatial arrangement. Chemical and structural characterization of the vaccine conjugates was followed by the study of cellular uptake and localization. Immune response was assayed by the measurement of splenocyte proliferation and cytokine production, while vaccine efficacy was studied in a murine model of tuberculosis. The conjugate showed higher tendency to fold and increased internalization rate into professional antigen presenting cells compared to free epitopes. Cellular uptake was further improved by the incorporation of a palmitoyl group to the conjugate and the resulted pal-A(P)I derivative possessed an internalization rate 10 times higher than the free epitope peptides. Vaccination of CB6F1 mice with free peptides resulted in low T-cell response. In contrast, significantly higher T-cell proliferation with prominent expression of IFN-γ, IL-2, and IL-10 cytokines was measured for the palmitoylated conjugate. Furthermore, the pal-A(P)I conjugate showed relevant vaccine efficacy against Mycobacterium tuberculosis infection.

The factor structure of posttraumatic stress disorder symptoms among Rwandans exposed to the 1994 genocide: A confirmatory factor analytic study using the PCL-C.

The factor structure of posttraumatic stress disorder (PTSD) symptoms in Euro-American populations has been extensively studied, but confirmatory factor analytic studies from non-Western societies are lacking. Alternative models of DSM-IV symptoms were tested among Rwandan adults (N=465) who experienced trauma during the 1994 genocide. A cluster random survey was conducted with interviews held in Rwandan households. PTSD was assessed with the Posttraumatic Stress Disorder Checklist-Civilian version. Competing models were the DSM-IV, emotional numbing, dysphoria, aroused intrusion, and dysphoric arousal models. Results showed that the emotional numbing, dysphoria, and dysphoric arousal models had almost identical, good fit indices and fit the data significantly better than the other models. The emotional numbing and dysphoric arousal models also exhibited good construct validity. Results suggest that the latent structure of PTSD symptoms in Rwanda are comparable to that found in Euro-American samples, thereby lending further support to the cross-cultural validity of the construct.

High-level cellular and humoral immune responses in Guinea pigs immunized intradermally with a heat-inactivated varicella-zoster virus vaccine.

The threat of varicella and herpes zoster in immunocompromised individuals necessitates the development of a safe and effective varicella-zoster virus (VZV) vaccine. The immune responses of guinea pigs to the intradermal (i.d.) or subcutaneous (s.c.) administration of a heat-inactivated or live VZV vaccine were investigated. Relative to nonimmunized animals, a single 399-PFU dose of vaccine induced nonsignificant increases in gamma interferon (IFN-γ), granzyme B, and perforin mRNA expression in the splenocytes of all groups, while two i.d. administrations of the inactivated vaccine increased IFN-γ mRNA expression significantly (P < 0.005). A single 1,995-PFU dose significantly increased the expression of IFN-γ mRNA in the groups receiving the vaccine either i.d. (P < 0.005) or s.c. (P < 0.05), that of granzyme B mRNA in the groups immunized i.d. with the inactivated (P < 0.005) or live (P < 0.005) vaccine, and that of perforin mRNA in the animals that received the inactivated vaccine i.d. (P < 0.005). Importantly, increases in the expression of IFN-γ (P = 0.025), granzyme B (P = 0.004), and perforin (P > 0.05) mRNAs were observed in the animals immunized i.d. with 1,995 PFU of inactivated vaccine relative to those immunized s.c. with the same dose. The proportion of animals expressing IFN-γ mRNA mirrored the proportion expressing IFN-γ protein (correlation coefficient of 0.88). VZV glycoprotein-specific and virus-neutralizing antibodies were produced with no significant intergroup differences. A booster i.d. administration of the 399-PFU dose of heat-inactivated vaccine enhanced the antibody responses. These results demonstrate that i.d. administration of an inactivated VZV vaccine can be an efficient mode of immunization against VZV.

Antimycobacterial activity of peptide conjugate of pyridopyrimidine derivative against Mycobacterium tuberculosis in a series of in vitro and in vivo models.

New pyridopyrimidine derivatives were defined using a novel HTS in silico docking method (FRIGATE). The target protein was a dUTPase enzyme (EC 3.6.1.23; Rv2697) which plays a key role in nucleotide biosynthesis of Mycobacterium tuberculosis (Mtb). Top hit molecules were assayed in vitro for their antimycobacterial effect on Mtb H37Rv culture. In order to enhance the cellular uptake rate, the TB820 compound was conjugated to a peptid-based carrier and a nanoparticle type delivery system (polylactide-co-glycolide, PLGA) was applied. The conjugate had relevance to in vitro antitubercular activity with low in vitro and in vivo toxicity. In a Mtb H37Rv infected guinea pig model the in vivo efficacy of orally administrated PLGA encapsulated compound was proven: animals maintained a constant weight gain and no external clinical signs of tuberculosis were observed. All tissue homogenates from lung, liver and kidney were found negative for Mtb, and diagnostic autopsy showed that no significant malformations on the tissues occurred.

Influence of feeding intensity on the growth, body composition and sexual maturity of male New Zealand White rabbits.

An experiment was carried out with young male New Zealand White (NZW) rabbits to establish live body weight changes, body measurements, body composition and sexual maturity as a function of feeding intensity. Animals in Group 1 ('AL', n = 10) were fed ad libitum, while those in Group 2 ('RS', n = 10) received restricted feeding corresponding to 70% of the ad libitum level. The starting liveweights were practically the same (0.907 +/- 0.146 and 0.911 +/- 0.147 kg in Group AL and Group RS, respectively). The feeding trial lasted from 6 to 22 weeks of age. The average body weight was significantly higher in Group AL from 7 to 22 weeks of age. At 22 weeks of age the body weight of RS rabbits was 85.64% of the weight of AL animals (3.22 +/- 0.52 kg and 3.76 +/- 0.33 kg, respectively). Average body weights of RS males at 8, 9, 11, 19 and 21 weeks of age were similar to those of ad libitum fed (AL) animals at 7, 8, 10, 15 and 16 weeks of age, respectively. The growth of bucks fed restricted tended to be allometric. The most significant difference was found at 16 and 18 weeks of age, while the lowest difference occurred at 6, 12, 15 and 19 weeks of age. It can be stated that low-intensity feeding up to slaughtering weight causes backwardness in rear cannon length and this backwardness remains also after the 15th week, which is well over the optimal slaughtering age. Based on the present data, the 70% restricted feeding cannot be recommended either for the future breeding bucks or for broiler males reared for slaughter. To determine the major chemical components of the body, rabbits were euthanised. Original dry matter and crude fat content of the body significantly (P < 0.05) decreased under restricted feeding (41.42%; 32.48% and 16.73%; 7.35%) while the percentage of protein within the dry matter increased (49.6%; 65.0%) and fat decreased (40.17%; 22.1%) significantly. Libido unambiguously decreases as a consequence of feed deprivation. The most conspicuous difference was found in the level of blood testosterone. Although a few RS bucks produced semen but only much later than the rabbits fed ad libitum. On the other hand, there was no difference in the motility of spermatozoa and ejaculate volume in comparison with AL animals. There was no relationship between the body fat content and the reproductive status of bucks in the present trial.

Is traumatic stress research global? A bibliometric analysis.

BACKGROUND: The representation of low- and middle-income countries (LMIC) in traumatic stress research is important to establish a global evidence base, build research capacity, and reduce the burden of unmet mental health needs around the world. Reviews of the traumatic stress literature up to 2002 showed trends toward globalization although LMIC were only marginally represented compared to high-income countries (HIC). OBJECTIVE: To examine the global nature of current traumatic stress research. In particular, we were interested in the extent to which traumatic stress research is: (1) conducted in LMIC, (2) conducted by LMIC researchers, and (3) accessible to them. METHOD: Using the databases PubMed, PsychInfo, and PILOTS, we systematically searched for peer-reviewed articles on traumatic stress published in any language in the year 2012. Out of the 3,123 unique papers identified, we coded a random sample (N=1,000) for study, author, article, and journal characteristics. RESULTS: Although our sample involved research in 56 different countries, most papers (87%) involved research in HIC, with 51% of all papers describing studies in the United States. In 88% of the papers, the author team was affiliated with HIC only. Less than 5% of all author teams involved collaborations between HIC and LMIC researchers. Moreover, 45% of the articles on LMIC studies published by a HIC corresponding author did not involve any LMIC co-authors. LMIC researchers appeared to publish empirical studies in lower impact journals. Of the 1,000 articles in our sample, 32% were open access and 10% were made available via different means; over half of the papers were not accessible without subscription. CONCLUSIONS: Traumatic stress research is increasingly global but still strongly dominated by HIC. Important opportunities to build capacity in LMIC appear to be missed. Implications toward more international traumatic stress research are discussed.

Does a study focused on trauma encourage patients with psychotic symptoms to seek treatment?

OBJECTIVE: This study explored, in a randomized trial of psychotherapies for posttraumatic stress disorder (PTSD), why a surprisingly high percentage of study applicants presented with psychotic symptoms and what clinical implications this finding might prompt. METHODS: Raters reviewed the records of applicants who completed an initial psychiatric interview and compared those who had psychotic symptoms with all other study-eligible participants and with those who ultimately were enrolled in the study. RESULTS: Of 223 consecutively evaluated individuals who applied for study entry, 38 (17%) were found ineligible because of psychotic symptoms. These individuals were more likely to be male and to have suffered child abuse, and they had taken a greater number of lifetime medications than study-eligible applicants. Most individuals with psychotic symptoms met DSM-IV criteria for PTSD. CONCLUSIONS: A trauma-informed framework might be a helpful part of a comprehensive treatment plan for some individuals with psychotic symptoms, possibly leading to greater treatment engagement and more positive outcomes.