Fluorescein and indocyanine-green angiography in ocular syphilis: an exploratory study.

BACKGROUND: Fluorescein (FA) and indocyanine-green angiography (ICGA) may offer valuable information concerning disease severity and prognosis in ocular syphilis. The aim of the present study is to describe angiographic patterns encountered in the context of ocular syphilis, and to explore the associations between specific angiographic manifestations and severity of disease presentation, as well as disease evolution after treatment. METHODS: We performed a retrospective institutional study with the inclusion of 23 patients with ocular syphilis presenting to the uveitis clinic of the Jules-Gonin Eye Hospital in a 10-year period. FA and ICGA were performed following a standard protocol for posterior uveitis. Patterns of fluorescence were noted, and statistical associations between each angiographic pattern and any demographic, clinical, or laboratory parameter at baseline and after treatment were sought. RESULTS: The presence of any dark dots in ICGA was significantly associated with anterior uveitis (p = 0.031). The presence of hot spots in ICGA was significantly associated with longer duration of symptoms prior to initial visit (p = 0.032) and with male gender (p = 0.012). Weak non-significant trends were found associating vascular staining in FA with anterior uveitis (p = 0.066), vitritis (p = 0.069), and younger age (p = 0.061), as well as disc hyperfluorescence in FA with seropositivity for HIV (p = 0.089) and macular edema in FA with longer disease duration (p = 0.061). The presence of any dark dots in ICGA exhibited a weak trend of association with anterior uveitis and/or vitritis (p = 0.079). CONCLUSIONS: Out of the several associations identified implicating specific angiographic features, we underline the possible role of the presence of dark dots in ICGA for identifying active inflammation, and the role of hot spots in ICGA as markers of long-standing disease. Vascular staining in FA appears to be more common in patients with severe ocular inflammation with presence of anterior uveitis and/or vitritis.

Development of targeted therapies in advanced gastric cancer: promising exploratory steps in a new era.

PURPOSE OF REVIEW: Many chemotherapeutic drugs, including fluoropyrimidines, platinums, CPT-11, taxanes and adriamycin have single-agent activity in advanced gastric cancer. Although combination chemotherapy has been shown to be more effective than single agents, response rates between 30 and 50% have not fulfilled their promise as progression-free survival from the best combinations ranges between 3 and 7 months and overall survival between 8 and 11 months. The development of targeted therapies in gastric cancer clearly stays behind the integration of these novel agents into new treatment concepts for patients with colorectal cancer. This review summarizes the experience and major recent advances in the development of targeted therapies in advanced gastric cancer. RECENT FINDINGS: Recent publications on targeted therapies in gastric cancer are limited to nonrandomized phase I or II trials. The majority of agents tested were angiogenesis inhibitors or agents targeting the epidermal growth factor receptors epidermal growth factor receptor 1 and HER2. SUMMARY: Adequately powered, randomized phase III trials are necessary to define the clinical role of targeted therapies in advanced gastric cancer. Biomarker studies to correlate with treatment outcomes will be critical to identify patients who benefit most from chemotherapy and targeted therapy.

Communication skills training and clinicians' defenses in oncology: an exploratory, controlled study.

Objective: The underlying mechanisms modifying clinician's communication skills by means of communication skills training (CST) remain unknown. Defense mechanisms, defined as psychological processes protecting the individual against emotional stress, may be a mediating factor of skills improvement.Methods: Using an adapted version of the Defense Mechanism Rating Scale-Clinician, this study evaluated clinicians' defense mechanisms and their possible modification after CST. Interviews with simulated patients of oncology clinicians (N=57) participating in CST (pre-/post-CST with a 6-month interval) were compared WITH interviews with the same simulated patients of oncology clinicians (N=56) who did not undergo training (T1 and T2 with a 6-month interval).Results: Results showed (i) a high number (mean=16, SD=6) and variety of defenses triggered by the 15-min interviews, (ii) no evolution difference between groups, and (iii) an increase in mature defenses after CST for clinicians with an initial higher level of defensive functioning.Conclusions: This is the first study describing clinicians' defensive functioning; results indicate a possible mediating role of defenses in clinician-patient communication.

Startegy selection during exploratory behavior: sex differences, uncertainty and risk managment

This study deals with the psychological processes underlying the selection of appropriate strategy during exploratory behavior. A new device was used to assess sexual dimorphisms in spatial abilities that do not depend on spatial rotation, map reading or directional vector extraction capacities. Moreover, it makes it possible to investigate exploratory behavior as a specific response to novelty that trades off risk and reward. Risk management under uncertainty was assessed through both spontaneous searching strategies and signal detection capacities. The results of exploratory behavior, detection capacities, and decision-making strategies seem to indicate that women's exploratory behavior is based on risk-reducing behavior while men behavior does not appear to be influenced by this variable. This difference was interpreted as a difference in information processing modifying beliefs concerning the likelihood of uncertain events, and therefore influencing risk evaluation.

Early tailored assertive community case management for hard-to-engage adolescents suffering from psychiatric disorders: an exploratory pilot study.

AIM: The study aims to evaluate the effects of assertive community treatment (ACT) on the mental health and overall functioning of adolescents suffering from severe psychiatric disorders and who refuse any traditional child psychiatric care. There are a few studies evaluating the effects of ACT on a population of adolescents with psychiatric disorders. This short report highlights the impact of an ACT programme tailored to the needs of these patients, not only as an alternative to hospitalization, but also as a new form of intervention for patients that are difficult to engage. METHODS: The effect of ACT on 35 adolescents using the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA) as a measuring tool in pre- and post-intervention was evaluated. RESULTS: The results show that the intervention was associated with a significant improvement on the HoNOSCA overall score, with the following items showing significant amelioration: hyperactivity/focus problems, non-organic somatic symptoms, emotional symptoms, scholastic/language skills, peer relationships, family relationships and school attendance. CONCLUSION: ACT appears as a feasible intervention for hard-to-engage adolescents suffering from psychiatric disorders. The intervention seems to improve their mental health and functioning. This pilot study may serve as a basis to prepare a controlled study that will also take the costs of the intervention into account.

Observer-rated Coping Associated with Borderline Personality Disorder: An Exploratory Study.

BACKGROUND: Little is known about coping specificities, as operationalization of the concept of affect regulation, in borderline personality disorder (BPD). It is most important to take into account methodological criticisms addressed to the self-report questionnaire approach and to compare BPD coping specificities to the ones of neighbouring diagnostic categories, such as bipolar disorder (BD). SAMPLING AND METHODS: The present exploratory study compared the coping profiles of N = 25 patients presenting BPD to those of N = 25 patients presenting BD and to those of N = 25 healthy controls. All participants underwent a clinical interview that was transcribed and rated using the Coping Patterns observer-rater system. RESULTS: Results partially confirmed study hypotheses and showed differences between BPD patients and healthy controls in all coping domains (competence, resources and autonomy), whereas the only coping domain presenting a BPD-specific lack of skills, compared with the BD patients, was autonomy, a set of coping strategies facing stress appraised as challenge. These coping processes were linked to general and BPD symptomatology. CONCLUSIONS: These results extend conclusions of earlier studies on affect regulation processes in BPD and bear important clinical implications, in the context of dialectical behavior therapy and other therapeutic approaches. Limitations of this exploratory study, such as the small sample size, are acknowledged. Copyright © 2012 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Coping can be reliably assessed in the narrative process in an non-structured interview frame. Patients with borderline personality disorder present with a specific lack of skills in affect regulation related to autonomy issues, compared to patients with bipolar disorder and healthy controls. Lack of skills in accommodation to distressing emotions in borderline personality disorder is related to symptom gravity and may be treated using radical acceptance strategies.

Impact of job insecurity on sexual desire: an exploratory analysis.

To explore, for the first time, the impact of job insecurity on sexual desire. Cross-sectional analysis of a nationally representative sample of 7247 individuals aged 20-64 years working as full or part-time employees in Switzerland. The logistic regression analysis showed that workers aged 20-49 years perceiving high levels of job insecurity are exposed to a significantly higher risk of decrease of sexual desire compared to the reference group. The risk is 53% higher among men (OR 1.53; 95% CI 1.16-2.01) and 47% for woman (OR 1.47; 1.13-1.91). No increased risk was found for employees aged 50-64 years old. An increasing fear of job loss is associated with a deterioration in sexual desire. These first preliminary findings should promote further epidemiological and clinical prospective studies on the impact of job insecurity on intimate relationships and sexual dysfunction.

Impact on assertivity of a social skills training with adolescents suffering from psychotic or anxiety/mood disorders: An exploratory study

During adolescence numerous of important social abilities are acquired within interactions with peers. Severe psychiatric disorders interfere with the acquisition of these social skills. For example, due to excessive shyness, adolescents with psychiatric disorders may not experiment positive social interactions. Social skills training (SKT) may help adolescents to remediate to these diffi culties. This exploratory study aims to assess the SKT's effect on assertivity, in a population of adolescents presenting psychiatric disorder and attending a day care unit for adolescents. The SKT, delivered in group, deals with different themes such as contact, conversation, problem solving, confl ict, fail, success, learning, effort, separation, breakdown, and project. In this context, 38 adolescents (19 suffering from anxiety / mood disorder and 19 suffering from psychotic disorder) rate their level of assertivity before and after a SKT with the Rathus assertivity scale. This scale allows to differentiate between inhibited, assertive and assertiveaggressive adolescents. Results showed a general improvement on assertivity after the SKT. More specifi cally, adolescents suffering from anxiety disorder and the 'inhibited' adolescents showed the higher benefi t from the SKT. Thus, two hours per week of SKT seems to enhance social abilities in a population with severe psychiatric disorders. More specifi - cally, adolescents with anxiety / mood disorders reported more benefi ts of the SKT on their assertivity. Nevertheless, adolescents with psychotic disorders did not report strong benefi ts from the SKT despite the improvement observed at a clinical level. This observation raises questions about the usefulness of self-reported questionnaire to measure such benefi t for adolescents with psychosis.

How Does Addressing Patient's Defenses Help to Repair Alliance Ruptures in Psychodynamic Psychotherapy?: An Exploratory Study.

Interpreting or addressing defenses is an important aspect of psychoanalytic technique. Previous research has shown that therapist addressing defenses (TADs) can produce a positive effect on alliance. The potential value of TADs during the process of alliance rupture and resolution has not yet been documented. We selected patients (n = 17) undertaking a short-term dynamic psychotherapy in which the therapeutic alliance, measured with the Helping Alliance Questionnaire and monitored after each session, showed a pattern of rupture and resolution. Two control sessions (5 and 15) were also selected. Presence of TADs was examined in each therapist interpretation. Compared with control sessions, rupture sessions were characterized by fewer TADs and especially fewer TADs addressing specifically intermediate-essentially neurotic-defenses. Resolution sessions were characterized by more TADs addressing specifically intermediate defenses. This confirms the link between therapist technique and alliance process in psychodynamic psychotherapy.

Maladaptive exploratory behavior and neuropathology of the PS-1 P117L Alzheimer transgenic mice.

Patients with the early-onset Alzheimer's disease P117L mutation in the presenilin-1 gene (PS-1) present pathological hallmarks in the hippocampus, the frontal cortex and the basal ganglia. In the present work we determined by immunohistochemistry which brain regions were injured in the transgenic PS-1 P117L mice, in comparison to their littermates, the B6D2 mice. Furthermore, as these regions are involved in novelty detection, we investigated the behavior of these mice in tests for object and place novelty recognition. Limited numbers of senile plaques and neurofibrillary tangles were detected in aged PS-1 P117L mice in the CA1 only, indicating that the disease is restrained to an initial neuropathological stage. Western blots showed a change in PSD-95 expression (p=0.03), not in NR2A subunit, NR2B subunit and synaptophysin expressions in the frontal cortex, suggesting specific synaptic alterations. The behavioral tests repeatedly revealed, despite a non-significant preference for object or place novelty, maladaptive exploratory behavior of the PS-1 P117L mice in novel environmental conditions, not due to locomotor problems. These mice, unlike the B6D2 mice, were less inhibited to visit the center of the cages (p=0.01) and they continued to move excessively in the presence of a displaced object (p=0.021). Overall, the PS-1 P117L mice appear to be in an initial Alzheimer's disease-like neuropathological stage, and they showed a lack of reaction toward novel environmental conditions.

The timing of exploratory decision-making revealed by single-trial topographic EEGanalyses.

Decision-making in an uncertain environment is driven by two major needs: exploring the environment to gather information or exploiting acquired knowledge to maximize reward. The neural processes underlying exploratory decision-making have been mainly studied by means of functional magnetic resonance imaging, overlooking any information about the time when decisions are made. Here, we carried out an electroencephalography (EEG) experiment, in order to detect the time when the brain generators responsible for these decisions have been sufficiently activated to lead to the next decision. Our analyses, based on a classification scheme, extract time-unlocked voltage topographies during reward presentation and use them to predict the type of decisions made on the subsequent trial. Classification accuracy, measured as the area under the Receiver Operator's Characteristic curve was on average 0.65 across 7 subjects. Classification accuracy was above chance levels already after 516 ms on average, across subjects. We speculate that decisions were already made before this critical period, as confirmed by a positive correlation with reaction times across subjects. On an individual subject basis, distributed source estimations were performed on the extracted topographies to statistically evaluate the neural correlates of decision-making. For trials leading to exploration, there was significantly higher activity in dorsolateral prefrontal cortex and the right supramarginal gyrus; areas responsible for modulating behavior under risk and deduction. No area was more active during exploitation. We show for the first time the temporal evolution of differential patterns of brain activation in an exploratory decision-making task on a single-trial basis.

SIRT1 Activates MAO-A in the Brain to Mediate Anxiety and Exploratory Drive.

SIRT1 is a NAD(+)-dependent deacetylase that governs a number of genetic programs to cope with changes in the nutritional status of cells and organisms. Behavioral responses to food abundance are important for the survival of higher animals. Here we used mice with increased or decreased brain SIRT1 to show that this sirtuin regulates anxiety and exploratory drive by activating transcription of the gene encoding the monoamine oxidase A (MAO-A) to reduce serotonin levels in the brain. Indeed, treating animals with MAO-A inhibitors or selective serotonin reuptake inhibitors (SSRIs) normalized anxiety differences between wild-type and mutant animals. SIRT1 deacetylates the brain-specific helix-loop-helix transcription factor NHLH2 on lysine 49 to increase its activation of the MAO-A promoter. Both common and rare variations in the SIRT1 gene were shown to be associated with risk of anxiety in human population samples. Together these data indicate that SIRT1 mediates levels of anxiety, and this regulation may be adaptive in a changing environment of food availability.