A feasibility study of microwave therapy for precancerous actinic keratosis.

BACKGROUND: Actinic keratosis (AK) is a common premalignant skin lesion that can progress to cutaneous squamous cell carcinoma (cSCC). Microwave therapy is an established cancer treatment and has been used for plantar viral warts. OBJECTIVES: To evaluate the efficacy and feasibility of microwave as a treatment for AK. METHODS: Stage I was a dose-setting study, in which seven participants had the dielectric properties of 12 thick and 22 thin AKs assessed for optimization of the microwave dose used for treatment in Stage II. Stage II was a randomized, internally controlled trial evaluating 179 AKs in 11 patients (93 treated, 86 untreated controls) on the scalp/forehead or dorsal hand. Participants received one treatment initially and a repeat treatment to unresolved AKs at week 4. The response was assessed at six visits over 4 months. The primary outcome was partial or complete resolution of the treated AKs. RESULTS: A significantly higher proportion of treated AK areas responded than untreated (90% vs. 15%; P < 0·001). Thin AKs were more responsive than thick AKs. The site did not affect efficacy. Pain was severe, but brief (80% reported pain lasting 'a few seconds only'). Adverse effects were minimal (erythema, n = 6; flaking, n = 3; itch, n = 3). All participants who would chose microwave therapy over their current treatment cited the shorter discomfort period. CONCLUSIONS: Microwave therapy is a portable, safe and effective treatment for AK. An easy-to-deliver, acceptable therapy for AK is attractive as a prevention strategy. While these results are promising, a larger randomized controlled trial is needed against an effective comparator to confirm clinical efficacy and patient acceptability. What is already known about this topic? Actinic keratoses (AKs) are common precancerous skin lesions. Successful treatment of AK can prevent cutaneous squamous cell carcinoma (cSCC). Most topical therapies for AK require repeated application over weeks and drive local skin inflammation, leading to poor compliance. An easy-to-deliver and effective treatment for AK, suitable for use in primary care, could reduce cSCC. What does this study add? Microwave therapy is a feasible, effective treatment for AK. Ninety per cent of treated AKs showed full or partial resolution at 120 days post-treatment. Microwave therapy was painful, but the pain was short-lived (seconds) and this short discomfort period was cited as the main reason that microwave was preferred to their current treatment.

Neural Control of Vascular Function in Skeletal Muscle.

The sympathetic nervous system represents a fundamental homeostatic system that exerts considerable control over blood pressure and the distribution of blood flow. This process has been referred to as neurovascular control. Overall, the concept of neurovascular control includes the following elements: efferent postganglionic sympathetic nerve activity, neurotransmitter release, and the end organ response. Each of these elements reflects multiple levels of control that, in turn, affect complex patterns of change in vascular contractile state. Primarily, this review discusses several of these control layers that combine to produce the integrative physiology of reflex vascular control observed in skeletal muscle. Beginning with three reflexes that provide somewhat dissimilar vascular patterns of response despite similar changes in efferent sympathetic nerve activity, namely, the baroreflex, chemoreflex, and muscle metaboreflex, the article discusses the anatomical and physiological bases of postganglionic sympathetic discharge patterns and recruitment, neurotransmitter release and management, and details of regional variations of receptor density and responses within the microvascular bed. Challenges are addressed regarding the fundamentals of measurement and how conclusions from one response or vascular segment should not be used as an indication of neurovascular control as a generalized physiological dogma. Whereas the bulk of the article focuses on the vasoconstrictor function of sympathetic neurovascular integration, attention is also given to the issues of sympathetic vasodilation as well as the impact of chronic changes in sympathetic activation and innervation on vascular health. © 2016 American Physiological Society.

Contraction-evoked vasodilation and functional hyperaemia are compromised in branching skeletal muscle arterioles of young pre-diabetic mice.

AIM: To investigate the effects of pre-diabetes on microvascular network function in contracting skeletal muscle. We hypothesized that pre-diabetes compromises contraction-evoked vasodilation of branching second-order (2A), third-order (3A) and fourth-order (4A) arterioles, where distal arterioles would be affected the greatest. METHODS: Intravital video microscopy was used to measure arteriolar diameter (in 2A, 3A and 4A) and blood flow (in 2A and 3A) changes to electrical field stimulation of the gluteus maximus muscle in pre-diabetic (The Pound Mouse, PD) and control (c57bl6, CTRL) mice. RESULTS: Baseline diameter and blood flow were similar between groups (2A: ~20 µm, 3A: ~14 µm and 4A: ~8 µm; 2A: ~1 nL s(-1) and 3A: ~0.5 nL s(-1) ). Single tetanic contraction (100 Hz; 200, 400, 800 ms duration) evoked rapid-onset vasodilation (ROV) and blood flow responses that were blunted by ~50% and up to 81%, respectively, in PD vs. CTRL (P < 0.05). The magnitude of ROV was up to 2-fold greater at distal arterioles (3A and 4A) vs. proximal arterioles (2A) in CTRL; however, in PD, ROV of only 4A was greater than 2A (P < 0.05). Rhythmic contraction (2 and 8 Hz, 30 s) evoked vasodilatory and blood flow responses that were also attenuated by ~50% and up to 71%, respectively, in PD vs. CTRL (P < 0.05). The magnitude of vasodilatory responses to rhythmic contraction was also up to 2.5-fold greater at 4A vs. 2A in CTRL; however spatial differences in vasodilation across arteriolar branch orders was disrupted in PD. CONCLUSIONS: Arteriolar dysregulation in pre-diabetes causes deficits in contraction-evoked dilation and blood flow, where greatest deficits occur at distal arterioles.

Defective TGF-beta signaling sensitizes human cancer cells to rapamycin.

mTOR, the mammalian target of rapamycin, is a critical target of survival signals in many human cancers. In the absence of serum, rapamycin induces apoptosis in MDA-MB-231 human breast cancer cells. However, in the presence of serum, rapamycin induces G(1) cell cycle arrest-indicating that a factor(s) in serum suppresses rapamycin-induced apoptosis. We report here that transforming growth factor-beta (TGF-beta) suppresses rapamycin-induced apoptosis in serum-deprived MDA-MB-231 cells in a protein kinase Cdelta (PKCdelta)-dependent manner. Importantly, if TGF-beta signaling or PKCdelta was suppressed, rapamycin induced apoptosis rather than G(1) arrest in the presence of serum. And, if cells were allowed to progress into S phase, rapamycin induced apoptosis in the presence of serum. BT-549 and MDA-MB-468 breast, and SW-480 colon cancer cells have defects in TGF-beta signaling and rapamycin induced apoptosis in these cells in the presence of either serum or TGF-beta. Thus, in the absence of TGF-beta signaling, rapamycin becomes cytotoxic rather than cytostatic. Importantly, this study provides evidence indicating that tumors with defective TGF-beta signaling--common in colon and pancreatic cancers--will be selectively sensitive to rapamycin or other strategies that target mTOR.

Acute head-down tilt decreases the postexercise resting threshold for forearm cutaneous vasodilation.

The purpose of this study was to evaluate the role of baroreceptor control on the postexercise threshold for forearm cutaneous vasodilation. On four separate days, six subjects (1 woman) were randomly exposed to 65 degrees head-up tilt and to 15 degrees head-down tilt during a No-Exercise and Exercise treatment protocol. Under each condition, a whole body water-perfused suit was used to regulate mean skin temperature (T(sk)) in the following sequence: 1) cooling until the threshold for vasoconstriction was evident; 2) heating ( approximately 7.0 degrees C/h) until vasodilation occurred; and 3) cooling until esophageal temperature (T(es)) and (T(sk)) returned to baseline values. The Exercise treatment consisted of 15 min of cycling exercise at 70% maximal O(2) uptake, followed by 15 min of recovery in the head-up tilt position. The No-Exercise treatment consisted of 30 min resting in the head-up tilt position. After the treatment protocols, subjects were returned to their pretreatment condition, then cooled and warmed again consecutively. The calculated T(es) threshold for cutaneous vasodilation increased 0.24 degrees C postexercise during head-up tilt (P < 0.05), whereas no difference was measured during head-down tilt. In contrast, sequential measurements without exercise demonstrate a time-dependent decrease for head-up tilt (0.17 degrees C) and no difference for head-down tilt. Pretreatment thresholds were significantly lower during head-down tilt compared with head-up tilt. We have shown that manipulating postexercise venous pooling by means of head-down tilt, in an effort to reverse its impact on baroreceptor unloading, resulted in a relative lowering of the resting postexercise elevation in the T(es) for forearm cutaneous vasodilation.

What is beyond the big five? Plenty!

In a recent analysis of personality data, Saucier and Goldberg (1998) sought to answer the question, What is beyond the Big Five? Those authors evaluated numerous clusters of English person-descriptive adjectives that have been suspected of referring to non-Big Five dimensions of personality. Their results led them to conclude that most, if not all, traits of personality can be adequately subsumed within the Big Five factor space. In contrast, our reanalysis of Saucier and Goldberg's own data, using a more realistic criterion for deciding on whether a variable does or does not fall within a particular factor space, contradicts their claim. We are led to the conclusion that there are plenty of dimensions of behavior beyond the Big Five.

Heritability of personality disorder traits: a twin study.

Genetic and non-genetic influences on the hierarchy of traits that delineate personality disorder as measured by the Dimensional Assessment of Personality Problems (DAPP-DQ) scale were examined using data from a sample of 483 volunteer twin pairs (236 monozygotic pairs and 247 dizygotic pairs). The DAPP-DQ assesses four higher-order factors, 18 basic dimensions and 69 facet traits of personality disorder. The correlation coefficients for monozygotic and dizygotic twin pairs ranged from 0.26 to 0.56 and from 0.03 to 0.41, respectively. Broad heritability estimates ranged from 0 to 58% (median value 45%). Additive genetic effects and unique environmental effects emerged as the primary influences on these scales, with unique environmental influences accounting for the largest proportion of the variance for most traits at all levels of the hierarchy.

Categorical distinctions in the study of personality disorder: implications for classification.

This article discusses the historical underpinnings of psychiatric classification and examines empirical evidence relevant to (a) whether personality disorders are distinct from each other and from normal personality and (b) whether personality disorders should be classified separately from other mental disorders. At the phenotypic level, research evidence strongly supports the use of a dimensional model to delineate personality disorders; evidence about their genotypic representation is less conclusive though still supportive. Neither empirical nor rational arguments indicate strong justification for separating personality disorders from other mental disorders, as has been done in both the third and fourth editions of the Diagnostic and Statistical Manual of Mental Disorders. Distinctions between abnormal and disordered personality are considered, and suggestions are made for more satisfactory diagnostic classificatory schemes.

Genetic and environmental contributions to dimensions of personality disorder.

OBJECTIVE: The authors estimated the heritability of the basic dimensions of personality disorder and the relative proportions of the variance attributable to genetic and environmental sources. METHOD: The subjects were 175 volunteer twin pairs (90 monozygotic and 85 dizygotic) from the general population. Each twin completed the Dimensional Assessment of Personality Pathology, a questionnaire that assesses 18 dimensions of personality disorder. The questionnaire was developed on the basis of factor analytic studies that identified a stable structure underlying personality disorders in clinical and nonclinical subjects. Structural equation model-fitting methods were used to estimate the influence of additive genetic, common environmental, and unique environmental effects. RESULTS: The estimates of broad heritability ranged from 0%, for conduct problems, to 64%, for narcissism. Behaviors associated with submissiveness and attachment problems had low heritability. For most dimensions, the best-fitting model was one that specified additive genetic and unique environmental effects. CONCLUSIONS: These results are similar to those reported for normal personality and suggest a continuity between normal and disordered personality.

Guidelines for developing, evaluating, and revising the classification of personality disorders.

The authors suggest ways to improve the classification of personality disorders by changing the way the classification is developed, evaluated, and modified. Specific proposals are intended to establish a system that can be evaluated and revised so that it successively approximates a valid system. The importance of stating the principles underlying the classification is emphasized. These principles include: the conception of personality disorder underlying each diagnosis, the structure used to define diagnoses, the nature of diagnostic items, and the model for organizing diagnostic decisions. A distinction is drawn among the theoretical, measurement, and diagnostic models underlying each diagnosis. The substantive aspects of the classification are discussed in terms of the evidence required to validate diagnostic concepts. It is argued that the first step in developing a classification is to ensure the content validity of diagnostic concepts because this is a prerequisite for other components of validity. Evaluation and revision of the classification are discussed in terms of the importance of convergent and discriminant evidence. It is recommended that the classification be evaluated and revised using criteria derived from the theoretical and measurement models associated with each diagnosis. It is also recommended that the classification be evaluated in terms of the degree to which diagnostic constructs are consistent across clinicians, different sets of diagnostic exemplars, and different samples of patients. Realization of these aims should provide a classification that may be verified, modified, or disproved in the scientific tradition.

The dimensionality of Type A behavior within a stressful work simulation.

The present study was conducted to examine the dimensionality of overt Type A behaviors elicited in a simulated stressful work environment. University students played a managerial role while being subjected to time and work-load pressures, and completed the Survey of Work Styles (SWS; Jackson & Gray, 1989). Eighteen behaviors, coded by two raters based on audiovisual recordings, yielded relatively high interrater reliabilities. Principal components analysis revealed four primary factors: Hurriedness, Irritability, Tension of the Lower Extremities, and Restlessness. These factors contribute to an understanding of Type A behavior in that they are the first to be derived from a purely observational approach rather than a combination of observational and self-report methods. Consistent with previous research, differential correlations between the factors and the SWS subscales supported a multi-dimensional interpretation of the Type A behavior pattern. Present findings are compared to those of previous studies of Type A dimensionality.

Factorial structure of traits delineating personality disorders in clinical and general population samples.

Categorical and dimensional models for classifying personality disorders were evaluated by comparing the structure of personality pathology in a clinical sample (n = 158) with the structure in a general population sample (n = 274). Subjects completed 100 personality scales. Separate factor analyses revealed similar structures in the 2 samples. An underlying structure in a combined sample showed limited agreement with the concepts of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1987). Fifteen factors were retained: Generalized Distress, Rejection, Restricted Expression, Compulsivity, Stimulus Seeking, Insecure Attachment, Diffidence, Intimacy Problems, Oppositionality, Interpersonal Disesteem, Conduct Problems, Cognitive Dysfunction, Affective Reactivity, Narcissism, and Social Apprehensiveness. The results are consistent with a dimensional representation of personality disorder.

Analysis of Multitrait-Multirater Performance Appraisal Data: Composite Direct Product Method versus Confirmatory Factor Analysis.

This study addresses the manner in which trait and rater variance combine in multitrait-multirater (MTMR) performance appraisal data. The Confirmatory Factor Analytic (CFA) model assumes trait and rater variance combine additively, whereas the Composite Direct Product (CDP) model assumes a multiplicative relationship. Implications of these models are explicated for MTMR data, and empirical differences are examined using four data sets. Results indicated that the fit of the CDP model was superior to that of the CFA model in all four data sets. Discussion centered on strengths and weaknesses of the CDP and CFA models, assumptions regarding trait/rater relationships and conflict between conceptual simplicity and realistic representation of relationships. Guidelines for applying the CDP method were provided.

Dimensions of personality pathology.

The reliability of DSM-III-R diagnoses of personality disorders is poor and their validity has yet to be established. There is little evidence that the features of personality pathology cluster into these diagnostic entities. For these reasons, it is important to explore alternative ways of classifying personality disorders. In this preliminary study, reliable scales were developed to assess 100 personality dimensions which were systematically developed. The factorial structure underlying the dimensions was evaluated in a heterogeneous sample of 110 subjects from the general population. Sixteen components, accounting for 81.4% of the variance, were retained for rotation to oblique structure. The components were labelled social avoidance, narcissism, insecure attachment, compulsive behaviours, interpersonal disesteem, mobility, anxiousness, conduct problems, stimulus seeking, identity disturbance, self-harm, rejection, diffidence, and hypersensitivity. Two components were not interpreted because they only had one or two salient loadings.

The relation between dominance, anger, and hormones in normally aging men: results from the Massachusetts Male Aging Study.

This paper examines the relation of two personality characteristics (dominance and anger) to hormones in normally aging men. The relation of the Jackson Personality Research Form E Dominance subscale and the Spielberger Anger Expression scale to serum levels of 17 endocrine variables, including testosterone (T) and dihydrotestosterone (DHT), cortisol, and prolactin, was examined in 1709 men aged 39 to 70 years randomly sampled from the Boston Metropolitan Statistical Area. Canonical correlation analysis resulted in the identification of a personality profile characterized as dominant with some aggressive behavior that tends to correlate with a hormonal pattern labeled the "availability of androgens." These results partially support previous findings in animals, adolescents, and criminal populations that "aggressive dominance" is related to testosterone.

Chronic parenting stress: moderating versus mediating effects of social support.

The present study contrasted the widely cited "buffer" model of social support with an alternative mediator model. Distinctions were drawn between the functions of social support under chronic vs. acute stress conditions, and between situation-specific stressors and major life events. Ongoing parenting stress was assessed in 96 mothers of deaf children and 118 matched controls. Tests of the competing models showed no moderating effects for social support. However, path analyses suggested that social support mediated the relationship between stressors and outcomes. Chronic parenting stress was associated with lowered perceptions of emotional support, and greater symptoms of depression and anxiety. Furthermore, parenting stress accounted for a substantial proportion of the variance in psychological distress scores in contrast to life event stress, which was only weakly related to psychological outcomes. The implications of mediational models for understanding adaptation to chronic stress are discussed.

Fetal gastroschisis and omphalocele: is cesarean section the best mode of delivery?

There has always been controversy regarding the mode of delivery of fetuses with abdominal wall defects. Prior studies may have been biased in this evaluation as a result of the effects of delay in repair, transport of the fetus to level III facilities, and antenatal diagnosis compared with an unsuspected diagnosis. The purpose of this study was to evaluate mode of delivery at level III institutions with access to complete care to determine if cesarean section improved outcome. One hundred eight infants were treated in the study period for abdominal wall defects. Fifty-six infants met all criteria for admission to the study. No difference in neonatal morbidity or mortality was identified. No difference was found in infants who were born by elective cesarean section compared with infants delivered after labor ensued. In conclusion, we found no evidence that cesarean section or avoidance of labor improved outcome in fetuses with uncomplicated abdominal wall defects.

The structured nonverbal assessment of personality.

This article describes the development of a structured nonverbal measure of personality based on Murray's (1938) system of needs. The items of the Nonverbal Personality Questionnaire consist of line drawings of a central figure performing trait-relevant behaviors in specific situations; respondents are asked to indicate the likelihood of engaging in similar behaviors. The nonverbal form was administered to three Canadian samples of respondents and one Finnish sample. Reliability and validity data for the initial item pool and for a revised form are reported. The utility of the nonverbal inventory for cross-cultural and theoretical work in personality is discussed.