Background and Objectives: Noninvasive bipolar and monopolar radiofrequency (RF) deep dermal heating devices have previously been described. A novel minimally invasive RF device employing a bipolar microneedle electrode system is introduced and its resultant thermal effects on human skin in vivo were characterized for the first time. Study Design/Materials and Methods: An investigational 35 W RF device was configured to operate in bipolar mode delivering energy directly within the dermis using 5 microneedle electrode pairs with real-time feedback of tissue temperature for treatment control. Superficial cooling was achieved using a Peltier device. A range of pulse durations between 1 and 25 seconds, and lesion temperatures between 60 and 80 C were tested in vivo on 15 human subjects. Thermal effects were assessed histologically using either hematoxylin & eosin (H&E) or nitroblue-tetrazoliumchloride (NBTC) staining. Treatment effects and adverse events were also monitored clinically. Results: The investigational bipolar RF device delivered controlled heating within dermal tissue. Histological staining with H&E revealed the presence of zones of denatured collagen within the reticular dermis. Lesions were generated at preselected temperatures between 60 and 80 C. Fractional lesions separated by zones of sparing as well as contiguous lesion patterns were demonstrated. Histological staining with H&E and NBTC revealed sparing of adnexal structures and adipose tissue. No major adverse events were observed. Conclusions: A novel fractional RF device utilizing a minimally invasive bipolar microneedle delivery system for the treatment of human tissue was developed. Treatment of 15 human subjects illustrated the controlled creation of dermally located thermal coagulation zones, herein known as radiofrequency thermal zones. We discovered that varying the pulse length allowed for fractional sparing of dermal tissue. To our knowledge, this is the first report to describe use of a direct real-time temperature and impedance feedback system to control energy delivery during deep dermal heating. Lasers Surg. Med. 41:87--95, 2009.

The early life environment has long-term implications for the risk of developing cardiovascular (CV) disease in adulthood. Fetal responses to changes in maternal nutrition may be of immediate benefit to the fetus, but the long-term effects of these adaptations may prove detrimental if nutrition in postnatal life does not match that predicted by the fetus on the basis of its prenatal environment. We tested this predictive adaptive response hypothesis with respect to CV function in sheep. We observed that a mismatch between pre-and postnatal nutrient environments induced an altered CV function in adult male sheep that was not seen when environments were similar. Sheep that received postnatal undernutrition alone had altered growth, CV function, and basal hypothalamo-pituitary-adrenal axis activity in adulthood. Prenatal undernutrition induced greater weight gain by weaning compared with the prenatal control diet, which may provide a reserve in the face of a predicted poor diet in later life. In an adequate postnatal nutrient environment (i.e., relatively mismatched), these offspring exhibited cardiac hypertrophy and altered CV function in adulthood. These data support the concept that adult CV function can be determined by developmental responses to intrauterine nutrition made in expectation of the postnatal nutritional environment, and that if these predictions are not met, the adult may be maladapted and at greater risk of CV disease. Our findings have substantial implications for devising strategies to reduce the impact of a mismatch in nutrition levels in humans undergoing rapid socio-economic transitions in both developing and developed societies.fetal development ͉ postnatal development ͉ predictive adaptive response

Research suggests that weight loss treatment generally benefits psychological well-being but these effects have never been quantitatively reviewed. A meta-analysis of 117 weight loss treatment tests showed that weight loss treatment was associated with lowered depression and increased self-esteem. Treatment type moderated treatment effects on depression and self-esteem. Actual weight loss moderated treatment effects on self-esteem but not depression; only treatments that produced actual weight loss predicted increased self-esteem whereas improvements in depression were independent of weight loss. The clinical implications of the findings and the possible causal relationships among weight, depression and self-esteem are discussed.

A mechanistic understanding of the pathology of psychiatric disorders has been hampered by extensive heterogeneity in biology, symptoms, and behavior within diagnostic categories that are defined subjectively. We investigated whether leveraging individual differences in information-processing impairments in patients with post-traumatic stress disorder (PTSD) could reveal phenotypes within the disorder. We found that a subgroup of patients with PTSD from two independent cohorts displayed both aberrant functional connectivity within the ventral attention network (VAN) as revealed by functional magnetic resonance imaging (fMRI) neuroimaging and impaired verbal memory on a word list learning task. This combined phenotype was not associated with differences in symptoms or comorbidities, but nonetheless could be used to predict a poor response to psychotherapy, the best-validated treatment for PTSD. Using concurrent focal noninvasive transcranial magnetic stimulation and electroencephalography, we then identified alterations in neural signal flow in the VAN that were evoked by direct stimulation of that network. These alterations were associated with individual differences in functional fMRI connectivity within the VAN. Our findings define specific neurobiological mechanisms in a subgroup of patients with PTSD that could contribute to the poor response to psychotherapy.

Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnosis can be problematic due to biases in self-disclosure of symptoms, stigma within military populations, and limitations identifying those at risk. Prior studies suggest that PTSD may be a systemic illness, affecting not just the brain, but the entire body. Therefore, disease signals likely span multiple biological domains, including genes, proteins, cells, tissues, and organism-level physiological changes. Identification of these signals could aid in diagnostics, treatment decision-making, and risk evaluation. In the search for PTSD diagnostic biomarkers, we ascertained over one million molecular, cellular, physiological, and clinical features from three cohorts of male veterans. In a discovery cohort of 83 warzone-related PTSD cases and 82 warzone-exposed controls, we identified a set of 343 candidate biomarkers. These candidate biomarkers were selected from an integrated approach using (1) data-driven methods, including Support Vector Machine with Recursive Feature Elimination and other standard or published methodologies, and (2) hypothesis-driven approaches, using previous genetic studies for polygenic risk, or other PTSD-related literature. After reassessment of ~30% of these participants, we refined this set of markers from 343 to 28, based on their performance and ability to track changes in phenotype over time. The final diagnostic panel of 28 features was validated in an independent cohort (26 cases, 26 controls) with good performance (AUC = 0.80, 81% accuracy, 85% sensitivity, and 77% specificity). The identification and validation of this diverse diagnostic panel represents a powerful and novel approach to improve accuracy and reduce bias in diagnosing combat-related PTSD.