The impact of hyperhomocysteinemia as a cardiovascular risk factor in the prediction of coronary heart disease.

Coronary heart disease often occurs in the absence of traditional risk factors. Consequently, epidemiological studies exploring novel risk factors are necessary to improve the prediction of coronary heart disease. This study evaluated five promising markers of cardiovascular risk: homocysteine, C-reactive protein, fibrinogen, lipoprotein(a) (Lp(a)), free apolipoprotein(a) (apo(a)) and Lp(a) phenotypes. The study included 135 patients with angiographically confirmed atherosclerosis. The control group consisted of 93 sex- and age-matched individuals. The Mann-Whitney U-test was used for group comparison. New risk factors were evaluated by binary logistic regression. The odds ratios were calculated continuously for homocysteine in dependence on C-reactive protein. Low density lipoprotein (LDL)-cholesterol was nearly identical in controls and patients. Homocysteine, C-reactive protein, fibrinogen, high density lipoprotein (HDL)-cholesterol and Lp(a) discriminated highly significantly between both groups. The continuously calculated odds ratio for homocysteine demonstrated a distinct influence of C-reactive protein. In the group with high C-reactive protein levels, homocysteine levels above 9.6 micromol/l resulted in a markedly elevated risk (odds ratio 12), in the group with C-reactive protein levels below 5 mg/dl, a comparable risk increase was observed at a homocysteine level of 16.6 micromol/l. This data strongly suggests that plasma homocysteine helps identify individuals at risk, especially among those with elevated C-reactive protein levels.     

Towards the use of diffuse reflectance spectroscopy for real-time in vivo detection of breast cancer during surgery

Background

Breast cancer surgeons struggle with differentiating healthy tissue from cancer at the resection margin during surgery. We report on the feasibility of using diffuse reflectance spectroscopy (DRS) for real-time in vivo tissue characterization.

Methods

Evaluating feasibility of the technology requires a setting in which measurements, imaging and pathology have the best possible correlation. For this purpose an optical biopsy needle was used that had integrated optical fibers at the tip of the needle. This approach enabled the best possible correlation between optical measurement volume and tissue histology. With this optical biopsy needle we acquired real-time DRS data of normal tissue and tumor tissue in 27 patients that underwent an ultrasound guided breast biopsy procedure. Five additional patients were measured in continuous mode in which we obtained DRS measurements along the entire biopsy needle trajectory. We developed and compared three different support vector machine based classification models to classify the DRS measurements.

Results

With DRS malignant tissue could be discriminated from healthy tissue. The classification model that was based on eight selected wavelengths had the highest accuracy and Matthews Correlation Coefficient (MCC) of 0.93 and 0.87, respectively. In three patients that were measured in continuous mode and had malignant tissue in their biopsy specimen, a clear transition was seen in the classified DRS measurements going from healthy tissue to tumor tissue. This transition was not seen in the other two continuously measured patients that had benign tissue in their biopsy specimen.

Conclusions

It was concluded that DRS is feasible for integration in a surgical tool that could assist the breast surgeon in detecting positive resection margins during breast surgery.Trail registration NIH US National Library of Medicine–clinicaltrails.gov, NCT01730365. Registered: 10/04/2012 https://clinicaltrials.gov/ct2/show/study/NCT01730365

     

Randomized Trial of the Parent And Caregiver Active Participation Toolkit for Child Mental Health Treatment

The purpose of this pilot study was to examine preliminary feasibility, acceptability, and effectiveness of a toolkit (Parent And Caregiver Active Participation Toolkit) to increase parent participation in community-based child mental health services. Study participants included 29 therapists (93% female; M age = 34.1 years; 38% Latino) and 20 parent/child dyads (children 80% female; M age = 8.6 years; parents 40% Latino) in 6 diverse community mental health clinics. Therapists were randomly assigned to standard care or the toolkit with standard care. Therapist and parent survey data and observational coding of treatment sessions were utilized. Mean comparisons and repeated measures analyses were used to test differences between study conditions over 4 months. Results supported preliminary feasibility and acceptability of the toolkit, with therapists assigned to the toolkit participating in ongoing training, adhering to toolkit use, and perceiving the toolkit as feasible and acceptable within their setting. Results preliminarily demonstrated improvement in therapists’ job attitudes, as well as actual use of parent engagement strategies. Results also preliminarily demonstrated increases in parent participation in child therapy sessions and more regular attendance, as well as some indication of support for perceived treatment effectiveness. Overall, results suggest the feasibility, acceptability, and potential effectiveness of the toolkit to enhance therapist job attitudes; practices that support parent engagement, parent engagement itself, and consumer perspectives on treatment outcomes; and the potential promise of future research in the area of parent participation interventions in child mental health services.     

Antiviral T Cells for Adenovirus in the Pretransplant Period: A Bridge Therapy for Severe Combined Immunodeficiency

Viral infections can be life threatening in patients with severe combined immunodeficiency (SCID) and other forms of profound primary immunodeficiency disorders both before and after hematopoietic stem cell transplantation (HSCT). Adoptive immunotherapy with virus-specific T cells (VSTs) has been utilized in many patients in the setting of HSCT, but has very rarely been attempted for treatment of viral infections before HSCT. Here we describe the use of VSTs in an infant with RAG1 SCID who had developed disseminated adenovirus which failed to improve on cidofovir. Adenovirus cleared following 2 doses of VSTs and marrow infusion from a matched unrelated donor, without incidence of graft versus host disease. T cell receptor-b sequencing demonstrated expansion of adenovirus-specific T cell fraction of the VSTs, suggesting that infusion facilitated viral clearance. This report suggests that VSTs are likely safe in the pre-HSCT period, and may be a useful bridge therapy for infants with SCID and persistent viral infections.     

From nature versus nurture, via nature and nurture, to gene × environment interaction in mental disorders

It is now generally accepted that complex mental disorders are the results of interplay between genetic and environmental factors. This holds out the prospect that by studying G × E interplay we can explain individual variation in vulnerability and resilience to environmental hazards in the development of mental disorders. Furthermore studying G × E findings may give insights in neurobiological mechanisms of psychiatric disorder and so improve individualized treatment and potentially prevention. In this paper, we provide an overview of the state of field with regard to G × E in mental disorders. Strategies for G × E research are introduced. G × E findings from selected mental disorders with onset in childhood or adolescence are reviewed [such as depressive disorders, attention-deficit/hyperactivity disorder (ADHD), obesity, schizophrenia and substance use disorders]. Early seminal studies provided evidence for G × E in the pathogenesis of depression implicating 5-HTTLPR, and conduct problems implicating MAOA. Since then G × E effects have been seen across a wide range of mental disorders (e.g., ADHD, anxiety, schizophrenia, substance abuse disorder) implicating a wide range of measured genes and measured environments (e.g., pre-, peri- and postnatal influences of both a physical and a social nature). To date few of these G × E effects have been sufficiently replicated. Indeed meta-analyses have raised doubts about the robustness of even the most well studied findings. In future we need larger, sufficiently powered studies that include a detailed and sophisticated characterization of both phenotype and the environmental risk.