Outer membrane vesicles derived from Bordetella pertussis are potent adjuvant that drive Th1-biased response.

For several years, we have been committed to exploring the potential of Bordetella pertussis-derived outer membrane vesicles (OMVBp) as a promising third-generation vaccine against the reemerging pertussis disease. The results of our preclinical trials not only confirm its protective capacity against B. pertussis infection but also set the stage for forthcoming human clinical trials. This study delves into the examination of OMVBp as an adjuvant. To accomplish this objective, we implemented a two-dose murine schedule to evaluate the specific immune response induced by formulations containing OMVBp combined with 3 heterologous immunogens: Tetanus toxoid (T), Diphtheria toxoid (D), and the SARS-CoV-2 Spike protein (S). The specific levels of IgG, IgG1, and IgG2a triggered by the different tested formulations were evaluated using ELISA in dose-response assays for OMVBp and the immunogens at varying levels. These assays demonstrated that OMVBp exhibits adjuvant properties even at the low concentration employed (1.5 µg of protein per dose). As this effect was notably enhanced at medium (3 µg) and high concentrations (6 µg), we chose the medium concentration to determine the minimum immunogen dose at which the OMV adjuvant properties are significantly evident. These assays demonstrated that OMVBp exhibits adjuvant properties even at the lowest concentration tested for each immunogen. In the presence of OMVBp, specific IgG levels detected for the lowest amount of antigen tested increased by 2.5 to 10 fold compared to those found in animals immunized with formulations containing adjuvant-free antigens (p<0.0001). When assessing the adjuvant properties of OMVBp compared to the widely recognized adjuvant alum, we detected similar levels of specific IgG against D, T and S for both adjuvants. Experiments with OMVs derived from E. coli (OMVE.coli) reaffirmed that the adjuvant properties of OMVs extend across different bacterial species. Nonetheless, it's crucial to highlight that OMVBp notably skewed the immune response towards a Th1 profile (p<0.05). These collective findings emphasize the dual role of OMVBp as both an adjuvant and modulator of the immune response, positioning it favorably for incorporation into combined vaccine formulations.

Trauma, risk, and resilience: A qualitative study of mental health in post-conflict Liberia.

The Liberian civil wars led to widespread destruction and devastation for its individuals, communities, and economy. However, individuals' subjective trauma experiences and long-term psychological impact remain relatively understudied. This study aims to explore context-specific traumatic events and examine how risk and protective factors combine with traumas to influence trajectories of suffering and recovery over time. We conducted 43 semi-structured interviews with Liberian adults who were present during the Liberian civil wars, and we used line-by-line open coding, thematic analysis, and axial coding to analyze and contextualize the data. Eight key trauma themes emerged: Abuse (emotional, physical, and sexual), Captivity, Combat, Killings, Physical Illness, Resource Loss, Family Separation, and War Environment. The risk and protective factors that were reported as salient were: Age, Biological Sex, Socioeconomic Status, and Community Support. Further, key patterns emerged across interviews that indicated greater risk for long-term suffering: 1) exposure to multiple traumatic events, 2) certain types of traumatic events (like killing of a close family member), and 3) the combination of specific traumatic events and risk and protective factors (like older women witnessing the killing of their children). This study provides culturally relevant information on trauma, suffering, and resilience in post-conflict Liberia, with the aim of guiding the development of screening tools and targeted psychological interventions that improve well-being over time.

Allogeneic Stem Cell Transplantation in Mature T Cell and Natural Killer/T Neoplasias: A Registry Study from Spanish GETH/GELTAMO Centers.

Despite advances in understanding the biology of mature T and natural killer (NK)/T cell neoplasia, current therapies, even the most innovative ones, are still far from ensuring its cure. The only treatment to date that has been shown to control aggressive T cell neoplasms in the long term is allogeneic stem cell transplantation (alloSCT). We aim to report the results of alloSCT for advanced mature T and NK/T neoplasias performed in centers from our national GELTAMO/GETH (Grupo Español de Linfoma y Trasplante de Médula Ósea/Grupo Español de Trasplante Hematopoyético y Terapia Celular) over the past 25 years. As a secondary objective, we analyzed the results of alloSCT from haploidentical donors. We performed a retrospective analysis of all patients who received an alloSCT in Spanish centers (n = 201) from September 1995 to August 2018. The 2-year overall survival (OS) and disease-free survival (DFS) were 65.5% and 58.2%, respectively. The univariate for OS and DFS showed statistically different hazard ratios for conditioning intensity, response pre-alloSCT, comorbidity index, donor/receptor cytomegalovirus status and Eastern Cooperative Oncology Group (ECOG) pre-alloSCT, but only a better ECOG pre-alloSCT remained significant in the multivariate analysis. There was an increased incidence of relapse in those patients who did not develop chronic graft-versus-host disease (GVHD) and an increased risk of death in those developing moderate to severe acute GVHD. The 1-year nonrelapse mortality was 21.9% and was mainly due to GVHD (30%) and bacterial infections (17%). When comparing unrelated donors with haploidentical donors, we found similar results in terms of OS and DFS. There was, however, a reduction of acute GVHD in the haploidentical group (P = .04) and trend to a reduction of chronic GVHD. In conclusion, alloSCT is the only curative option for most aggressive T cell neoplasias. Haploidentical donors offer similar results to related donors in terms of survival with a reduction of acute GVHD.

Defibrotide in hematopoietic stem cell transplantation: A multicenter survey study of the Spanish Hematopoietic Stem Cell Transplantation Group (GETH).

BACKGROUND: Defibrotide is approved in European Union for the treatment of severe sinusoidal obstruction syndrome (SOS) after HSCT. However, it has also been used for SOS prophylaxis, moderate SOS and in other complications such as transplant-associated thrombotic microangiopathy (TAM). The objective of this study was to evaluate current uses, effectiveness and safety of defibrotide in patients with HSCT. METHODS: This multicenter, retrospective study included patients treated with defibrotide for any indication at 28 HSCT centers of the Grupo Español de Trasplante Hematopoyetico (GETH) including the pediatric subgroup Grupo Español de Trasplante de Medula en Niños (GETMON). RESULTS: Three hundred and eighty eight patients treated with defibrotide between January 2011 and December 2018 were included. 253 patients were children, and 135 patients were adults. In total, 332 transplants were allogeneic, and the remainder were autologous. Main indications for defibrotide use were severe/very severe SOS in 173 patients, SOS prophylaxis in 135 patients, moderate SOS in 41 patients, TAM in six patients and suspected SOS in 33 patients. Overall survival (OS) at day +100 in the SOS prophylaxis group was 89% (95% CI, 87%-91%). In the group of patients with moderate and severe/very severe SOS, the OS at day +100 was 80% (95% CI, 74%-86%) and 62% (95% CI, 59%-65%), respectively (P = .0015). With a longer follow-up, median of 2 years (4 months-7 years), OS was 63% (95% CI, 59%-67%) in the SOS prophylaxis patients. OS for patients with moderate and severe/very severe SOS groups was 53% (95% CI, 47%-61%) and 26% (95% CI, 22%-30%), respectively (P = .006). 191 patients died, and SOS was the main cause of death in 23 patients (12%). CONCLUSIONS: Defibrotide has an acceptable safety profile with an improved response in severe/very severe SOS compared with historical controls, mainly in pediatric patients. Use of defibrotide for prophylaxis may improve prognosis of patients at high risk of complications due to endothelial damage such as those who receive a second transplant. SOS has an important impact on the HSCT long-term survival, as can be concluded from our study.

A mental health needs assessment of children and adolescents in post-conflict Liberia: results from a quantitative key-informant survey.

Between 1989 and 2004, Liberia experienced a devastating civil war that resulted in widespread trauma with almost no mental health infrastructure to help citizens cope. In 2009, the Liberian Ministry of Health and Social Welfare collaborated with researchers from Massachusetts General Hospital to conduct a rapid needs assessment survey in Liberia with local key informants (n = 171) to examine the impact of war and post-war events on emotional and behavioral problems of, functional limitations of, and appropriate treatment settings for Liberian youth aged 5-22. War exposure and post-conflict sexual violence, poverty, infectious disease and parental death negatively impacted youth mental health. Key informants perceived that youth displayed internalizing and externalizing symptoms and mental health-related functional impairment at home, school, work and in relationships. Medical clinics were identified as the most appropriate setting for mental health services. Youth in Liberia continue to endure the harsh social, economic and material conditions of everyday life in a protracted post-conflict state, and have significant mental health needs. Their observed functional impairment due to mental health issues further limited their access to protective factors such as education, employment and positive social relationships. Results from this study informed Liberia's first post-conflict mental health policy.

Relationships between positive psychological constructs and health outcomes in patients with cardiovascular disease: A systematic review.

Depression and anxiety are well-known to be associated with adverse health outcomes in cardiac patients. However, there has been less work synthesizing the effects of positive psychological constructs (e.g., optimism) on health-related outcomes in cardiac patients. We completed a systematic review of prospective observational studies using established guidelines. A search of PubMed and PsycINFO databases from inception to January 2014 was used to identify articles. To be eligible, studies were required to assess effects of a positive psychological construct on subsequent health-related outcomes (including mortality, rehospitalizations, self-reported health status) in patients with established heart disease. Exploratory random effects' meta-analyses were performed on the subset of studies examining mortality or rehospitalizations. Seventy-seven analyses from 30 eligible studies (N=14,624) were identified. Among studies with 100 or more participants, 65.0% of all analyses and 64.7% of analyses adjusting for one or more covariates reported a significant (p<.05) association between positive psychological constructs and subsequent health outcomes. An exploratory meta-analysis of 11 studies showed that positive constructs were associated with reduced rates of rehospitalization or mortality in unadjusted (odds ratio=.87; 95% confidence interval [.83, .92]; p<.001) and adjusted analyses (odds ratio=.89; 95% confidence interval [.84, .91]; p<.001); there was little suggestion of publication bias. Among cardiac patients, positive psychological constructs appear to be prospectively associated with health outcomes in most but not all studies. Additional work is needed to identify which constructs are most important to cardiac health, and whether interventions can cultivate positive attributes and improve clinical outcomes.

Epidemiology of major depression with atypical features: results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).

OBJECTIVE: To examine prevalence, correlates, comorbidity and treatment-seeking among individuals with a lifetime major depressive episode (MDE) with and without atypical features. METHOD: Data were derived from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions, a large cross-sectional survey of a representative sample (N = 43,093) of the US population that assessed psychiatric disorders using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version (AUDADIS-IV). Comparison groups were defined based on the presence or absence of hypersomnia or hyperphagia in individuals who met criteria for lifetime DSM-IV MDE. RESULTS: The presence of atypical features during an MDE was associated with greater rates of lifetime psychiatric comorbidity, including alcohol abuse, drug dependence, dysthymia, social anxiety disorder, specific phobia, and any personality disorder (all P values < .05), except antisocial personality disorder, than MDE without atypical features. Compared with the latter group, MDE with atypical features was associated with female gender, younger age at onset, more MDEs, greater episode severity and disability, higher rates of family history of depression, bipolar I disorder, suicide attempts, and larger mental health treatment-seeking rates (all P values < .05). CONCLUSIONS: Our data provide further evidence for the clinical significance and validity of this depressive specifier. Based on the presence of any of the 2 reversed vegetative symptoms during an MDE, most of the commonly cited validators of atypical depression were confirmed in our study. Major depressive episode with atypical features may be more common, severe, and impairing than previously documented.

Safe return to homeland of an illegal immigrant with psychosis.

The disposition of illegal immigrants who lack social support and wish to return to their homeland is a frequent and difficult challenge for many mental health facilities in the United States. This case involved an undocumented Mexican patient with severe psychosis who was safely transferred to his hometown according to his and his family's wishes through the use of specific services provided by the Mexican Consulate. We hope that publication of this case will make the medical community more aware of the availability of these underused services, which can make a major difference in the prognosis of some undocumented patients who would otherwise be left without resources or appropriate care.

Psychiatric disorders in pregnant and postpartum women in the United States.

CONTEXT: Psychiatric disorders and substance use during pregnancy are associated with adverse outcomes for mothers and their offspring. Information about the epidemiology of these conditions in this population is lacking. OBJECTIVE: To examine sociodemographic correlates, rates of DSM-IV Axis I psychiatric disorders, substance use, and treatment seeking among past-year pregnant and postpartum women in the United States. DESIGN: National survey. SETTING: Face-to-face interviews conducted in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions. PARTICIPANTS: A total of 43 093 respondents were interviewed, of whom 14 549 were women 18 to 50 years old with known past-year pregnancy status. MAIN OUTCOME MEASURES: Prevalence of 12-month DSM-IV Axis I psychiatric disorders, substance use, and treatment seeking. RESULTS: Past-year pregnant and postpartum women had significantly lower rates of alcohol use disorders and any substance use, except illicit drug use, than nonpregnant women. In addition, currently pregnant women had a lower risk of having any mood disorder than nonpregnant women. The only exception was the significantly higher prevalence of major depressive disorder in postpartum than in nonpregnant women. Age, marital status, health status, stressful life events, and history of traumatic experiences were all significantly associated with higher risk of psychiatric disorders in pregnant and postpartum women. Lifetime and past-year treatment-seeking rates for any psychiatric disorder were significantly lower among past-year pregnant than nonpregnant women with psychiatric disorders. Most women with a current psychiatric disorder did not receive any mental health care in the 12 months prior to the survey regardless of pregnancy status. CONCLUSIONS: Pregnancy per se is not associated with increased risk of the most prevalent mental disorders, although the risk of major depressive disorder may be increased during the postpartum period. Groups of pregnant women with particularly high prevalence of psychiatric disorders were identified. Low rates of maternal mental health care underscore the need to improve recognition and delivery of treatment for mental disorders occurring during pregnancy and the postpartum period.

Gender differences in generalized anxiety disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).

OBJECTIVE: To assess gender differences in the epidemiology, comorbidity, and treatment-seeking patterns of DSM-IV generalized anxiety disorder (GAD) in the United States. METHOD: Data were derived from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions, a large cross-sectional survey of a representative sample (N = 43,093) of the U.S. population. RESULTS: The lifetime and 12-month male:female prevalence ratios of DSM-IV GAD were 1:1.9 and 1:2.2, respectively. Men with GAD had significantly higher rates of comorbid alcohol and drug use disorders, nicotine dependence, and antisocial personality disorder. Women with GAD had significantly higher rates of comorbid mood disorders (except bipolar disorder) and anxiety disorders (except social anxiety disorder). Men with GAD reported greater use of alcohol and drugs to help relieve GAD symptoms. GAD in women was associated with higher rates of family history of depression. Disability associated with GAD was greater in women than in men. Rates of treatment seeking for DSM-IV GAD were low for both genders, but particularly low among men. CONCLUSION: There are significant gender differences in the prevalence, comorbidity pattern, sociodemographic and clinical correlates, course, and treatment-seeking rates of persons with DSM-IV GAD. Increased recognition and treatment of GAD, particularly among men, could lead to substantial reductions in the societal and personal burden and improve the quality of life of those afflicted with this disorder.