Modeling the development of acquired clinical immunity to Plasmodium falciparum malaria

Individuals living in regions where malaria is endemic develop an acquired immunity to malaria which enables them to remain asymptomatic while still carrying parasites. Field studies indicate that cumulative exposure to a variety of diverse Plasmodium parasites is required for the transition from symptomatic to asymptomatic malaria. This study used a simulation model of the within-host dynamics of P. falciparum to investigate the development of acquired clinical immunity under different transmission conditions and levels of parasite diversity. Antibodies developed to P. falciparum erythrocyte membrane protein 1 (PfEMP1), a clonally variant molecule, were assumed to be a key human immunological response to P. falciparum infection, along with responses to clonally conserved but polymorphic antigens. The time to the development of clinical immunity was found to be proportional to parasite diversity and inversely proportional to transmission intensity. The effect of early termination of symptomatic infections by chemotherapy was investigated and found not to inhibit the host's ability to develop acquired immunity. However, the time required to achieve this state was approximately double that compared to when no treatment was administered. This study demonstrates that an immune response primarily targeted against PfEMP1 has the ability to reduce clinical symptoms of infections irrespective of whether treatment is administered, supporting its role in the development of acquired clinical immunity. The results also illustrate a novel use for simulation models of P. falciparum infections, investigation of the influence of intervention strategies on the development of naturally acquired clinical immunity.     

Physical activity, aerobic fitness, and seven-year changes in adiposity in the Canadian population.

Associations among baseline physical activity, aerobic fitness, changes in physical activity, and 7-y changes in adiposity were determined. The sample consisted of 602 males and 644 females, aged 20-69 y, from the 1981 Canada Fitness Survey and the 1988 Campbell's Survey. Questionnaire-derived measures of physical activity level consisted of activity energy expenditure (AEE) and time spent on physical activity. Participants were grouped into physical activity level categories by AEE and physical activity intensity (based on MET values), and physical activity level changes were determined from movement between tertiles of AEE from baseline to follow-up. Aerobic fitness levels at baseline were determined using the Canadian Aerobic Fitness Test. Changes in body mass, the sum of five skinfolds (SF5), and waist circumference (WC) were used as indicators of adiposity change. ANCOVA and multiple regression analyses indicated that neither baseline physical activity levels, intensity, physical activity change categories, nor aerobic fitness levels were significant predictors of changes in adiposity. In conclusion, physical activity was not predictive of 7-y changes in indicators of adiposity in this sample.     

Treatment Options in Severe Psychotic Depression

In our sample of 15 hospitalized patients with severe psychotic depression, six responded to therapy with tricyclic antidepressants combined with neuroleptics. Of the nine nonresponders, eight showed an excellent clinical response to electroconvulsive therapy (ECT). The clinical outcome after 6 months of treatment was similar in both groups. We recommend that protracted, complicated trials of pharmacotherapy be reevaluated in psychotic depression. A prospective comparative study of ECT and pharmacotherapy is needed to define the optimal treatment for psychotic depression.     

When the universal is particular: a re-examination of the common morality using the work of Charles Taylor

Medicine, Health Care and Philosophy - Beauchamp and Childress’ biomedical principlism is nearly synonymous with medical ethics for most clinicians. Their four principles are theoretically...     

The cost of lost productivity due to premature mortality associated with COVID-19: a Pan-European study

The European Journal of Health Economics - Economic cost estimates have the potential to provide a valuable alternative perspective on the COVID-19 burden. We estimate the premature mortality...     

Local-Level Immigration Enforcement and Risk of Pediatric Hospitalization for Ambulatory Care Sensitive Conditions

Immigration enforcement may disrupt access to health care, potentially increasing hospitalizations for Ambulatory Care Sensitive Conditions (ACSC). We aimed to assess the effect of local-level 287(g) immigration enforcement on North Carolina pediatric ACSC hospitalizations. Pediatric (<?19 year) ACSC hospitalizations were identified based on ICD-9 codes. We compared ACSC hospitalizations pre and post 287(g) implementation using a difference-in-difference analysis of Fiscal Year (FY)2006-2009 data. We used multi-level models to assess the effects of 287(g) programs on ACSC hospitalizations during FY2011-2015. Difference-in-difference analyses showed that ACSC hospitalizations increased by more than 2.48% in the year following 287(g) implementation (95% CI: 0.99%, 3.97%). Among the counties that had ever implemented a 287(g) program, the ACSC-increasing effect of an active 287(g) program was greatest in counties with a shorter tenure of their 287(g) program and for Hispanic/Latino children/adolescents. Our findings underscore the importance of describing the effects of local-level immigration enforcement on pediatric access to care and potentially avoidable hospitalizations.

     

Heart Transplantation for Giant Cell Myocarditis: A Case Series

BackgroundGiant cell myocarditis (GCM) has a poor prognosis without heart transplant, but post-transplant survival is unknown.PurposeTo describe the post-transplant survival of patients with GCM at a large transplant center.MethodsSeven patients underwent heart transplant for histologically confirmed GCM of the explanted heart. The median age was 59 years, and 43% (3 of 7) were female. All patients had cardiogenic shock, multiorgan failure, elevated troponin, and recurrent ventricular tachycardia, and some required mechanical circulatory support. All patients received rabbit antithymocyte globulin (rATG) in the perioperative period at a dose of 1.5 mg/kg daily for 1 to 5 days and 4 received intravenous immunoglobulin 1 g/kg daily for 2 days after rATG. All patients had early initiation of tacrolimus by first to third postoperative day depending on renal function, early mycophenolate, and high dose steroid. All were maintained using tacrolimus, mycophenolate, and prednisone.ResultsOne patient had asymptomatic recurrence of GCM at 3 months, managed by up-titration of tacrolimus, and had asymptomatic 2R cellular rejection at 4 months, managed with steroid bolus. No patient had high-grade rejection. One patient died at 267 days, possibly of GCM. Six of 7 (86%) remain alive at a median of 842 days (2.3 years) post transplant.ConclusionsPatients with GCM have excellent post-transplant survival with use of rATG and triple drug immunosuppressive therapy; however, some patients remain at risk for GCM recurrence after transplant, which may respond to augmented immunosuppression.     

Is romantic partner betrayal a form of traumatic experience? A qualitative study

According to a growing body of research, betrayal by a romantic partner is increasingly considered as a form of interpersonal trauma. Between 30% and 60% of betrayed individuals experience symptoms of post-traumatic stress disorder (PTSD), depression and anxiety to clinically meaningful levels. From a clinical perspective, this constellation of symptoms can be conceptualized as a stressor-related adjustment disorder. Yet, no qualitative research has examined the association between romantic betrayal and traumatic stress from the perspective of betrayed individuals. Face-to-face semi-structured interviews were conducted with 13 participants who had completed a clinical trial for a new treatment for adjustment disorder stemming from betrayal. Data were analysed using thematic content analysis. Although betrayal was experienced as a shocking and destabilizing event, and participants used trauma or ‘feeling traumatized’ as a metaphor to describe their experience, few had constructed their reaction as traumatic stress. In fact, participants reported experiencing difficulties understanding the intensity of their experience. However, when exposed to external sources (e.g., books and interviews by psychologists and researchers) that used a trauma and PTSD framework to explain the effects of betrayal, participants reported feeling clarity, validation and relief. Findings are discussed in the light of theoretical and clinical implications.