Downregulation of dystrophin expression in pupae of the whitefly Bemisia tabaci inhibits the emergence of adults.

The whitefly Bemisia tabaci is a major pest to agriculture. Adults are able to fly for long distances and to colonize staple crops, herbs and ornamentals, and to vector viruses belonging to several important taxonomic groups. During their early development, whiteflies mature from eggs through several nymphal stages (instars I to IV) until adults emerge from pupae. We aim at reducing whitefly populations by inhibiting the emergence of adults from nymphs. Here we targeted dystrophin, a conserved protein essential for the development of the muscle system in humans, other animals and insects. We have exploited the fact that whitefly nymphs developing on tomato leaves feed from the plant phloem via their stylets. Thus, we delivered dystrophin-silencing double-stranded RNA to nymphs developing on leaves of tomato plantlets with their roots bathing in the silencing solution. Downregulation of dystrophin expression occurred mainly in pupae. Dystrophin silencing induced also the downregulation of the dystrophin-associated protein genes actin and tropomyosin, and disrupted F-actin. Most significantly, the treatment inhibited the emergence of adults from pupae, suggesting that targeting dystrophin may help to restrain whitefly populations. This study demonstrates for the first time the important role of dystrophin in the development of a major insect pest to agriculture.

The associations of earlier trauma exposures and history of mental disorders with PTSD after subsequent traumas.

Although earlier trauma exposure is known to predict posttraumatic stress disorder (PTSD) after subsequent traumas, it is unclear whether this association is limited to cases where the earlier trauma led to PTSD. Resolution of this uncertainty has important implications for research on pretrauma vulnerability to PTSD. We examined this issue in the World Health Organization (WHO) World Mental Health (WMH) Surveys with 34 676 respondents who reported lifetime trauma exposure. One lifetime trauma was selected randomly for each respondent. DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) PTSD due to that trauma was assessed. We reported in a previous paper that four earlier traumas involving interpersonal violence significantly predicted PTSD after subsequent random traumas (odds ratio (OR)=1.3-2.5). We also assessed 14 lifetime DSM-IV mood, anxiety, disruptive behavior and substance disorders before random traumas. We show in the current report that only prior anxiety disorders significantly predicted PTSD in a multivariate model (OR=1.5-4.3) and that these disorders interacted significantly with three of the earlier traumas (witnessing atrocities, physical violence victimization and rape). History of witnessing atrocities significantly predicted PTSD after subsequent random traumas only among respondents with prior PTSD (OR=5.6). Histories of physical violence victimization (OR=1.5) and rape after age 17 years (OR=17.6) significantly predicted only among respondents with no history of prior anxiety disorders. Although only preliminary due to reliance on retrospective reports, these results suggest that history of anxiety disorders and history of a limited number of earlier traumas might usefully be targeted in future prospective studies as distinct foci of research on individual differences in vulnerability to PTSD after subsequent traumas.

The epidemiology of traumatic event exposure worldwide: results from the World Mental Health Survey Consortium.

BACKGROUND: Considerable research has documented that exposure to traumatic events has negative effects on physical and mental health. Much less research has examined the predictors of traumatic event exposure. Increased understanding of risk factors for exposure to traumatic events could be of considerable value in targeting preventive interventions and anticipating service needs. METHOD: General population surveys in 24 countries with a combined sample of 68 894 adult respondents across six continents assessed exposure to 29 traumatic event types. Differences in prevalence were examined with cross-tabulations. Exploratory factor analysis was conducted to determine whether traumatic event types clustered into interpretable factors. Survival analysis was carried out to examine associations of sociodemographic characteristics and prior traumatic events with subsequent exposure. RESULTS: Over 70% of respondents reported a traumatic event; 30.5% were exposed to four or more. Five types - witnessing death or serious injury, the unexpected death of a loved one, being mugged, being in a life-threatening automobile accident, and experiencing a life-threatening illness or injury - accounted for over half of all exposures. Exposure varied by country, sociodemographics and history of prior traumatic events. Being married was the most consistent protective factor. Exposure to interpersonal violence had the strongest associations with subsequent traumatic events. CONCLUSIONS: Given the near ubiquity of exposure, limited resources may best be dedicated to those that are more likely to be further exposed such as victims of interpersonal violence. Identifying mechanisms that account for the associations of prior interpersonal violence with subsequent trauma is critical to develop interventions to prevent revictimization.

[Implementing mindfulness based therapies as part of the comprehensive treatments in the Beer Sheba Mental Health Center].

In recent years, there has been a growing interest and popularity in mindfulness-based therapies. Theories and practices that, until lately, have been considered esoteric and practiced in private by only a few therapists, are now progressively becoming part of mainstream establishment therapies and are gaining greater interest and recognition. The therapies can be carried out either in an individual or in a group setting and most include formal mindful sitting practice, developing awareness, mindful movement, psycho-education and often include a cognitive component. Furthermore, these therapies are becoming increasingly validated by widespread research pointing to promising results in the treatment of various cLinicaL disorders including anxiety, depression and relapse prevention, personality disorders, attention disorders and psychotic disorders, in both an in-patient and out-patient setting. The aim of this overview is to describe the deveLopment that has taken place in the fast decades within the field of mindfulness-based therapies and to present the most up-to-date research in this area: to show which therapeutic interventions have been proven to be effective; the background of the ideas; and the relevance of these approaches to the mental health system in Israel.

A painful train of events: increased prevalence of fibromyalgia in survivors of a major train crash.

OBJECTIVES: To evaluate the prevalence of fibromyalgia in survivors of a major train crash in southern Israel, three years after the event. METHODS: Survivors were contacted by mail and telephone. Individuals consenting to participate in the study underwent physical examination, including a tender point count and dolorimetry, as well as extensive evaluation of parameters relating to quality of life, presence of widespread pain, fatigue, physical and social function, posttraumatic symptoms and symptoms related to anxiety, dissociation, depression, somatisation, etc. RESULTS: Fifteen percent of survivors participating in the study met ACR criteria for the classification of fibromyalgia. Significantly lower rates of physical and emotional functioning were found among survivors with fibromyalgia compared with those not meeting the classification criteria. Survivors with fibromyalgia rated significantly higher on scales of somatisation, obsessive-compulsive ideation, interpersonal sensitivity, depression, anger and hostility, phobic and general anxiety, paranoid ideation and psychoticism. Survivors with fibromyalgia also rated significantly higher on scales of posttraumatic symptoms including intrusion, avoidance and arousal. These individuals also rated significantly higher on the Peritraumatic Dissociative Experiences Questionnaire (PDE-Q) and the Dissociative Experiences Scale (Hebrew version) (DES-H). CONCLUSION: Fibromyalgia was found to be highly prevalent, three years after a major train crash, among individuals exposed to the combination of physical injury and extreme stress. This finding is in accordance with previous data regarding the association of fibromyalgia with both physical and emotional trauma and calls attention to studying the underlying susceptibility factors which may partake in this association.

The protein CD63 is in platelet dense granules, is deficient in a patient with Hermansky-Pudlak syndrome, and appears identical to granulophysin.

The levels and expression of the proteins CD63 and granulophysin in platelets from control and from a Hermansky-Pudlak syndrome subject (a condition characterized by dense granule and lysosomal deficiencies and the accumulation of ceroid-like material in reticuloendothelial cells) were examined. Immunofluorescence studies indicated that anti-CD63 and anti-granulophysin antibodies recognized similar numbers of granules; coapplication of antibodies did not identify more granules than the individual antibodies. Significantly fewer granules were recognized in Hermansky-Pudlak syndrome platelets than in control using either antibody. Immunoblotting studies demonstrated that anti-CD63 and anti-granulophysin antibodies apparently recognize the same protein, which was deficient in Hermansky-Pudlak platelets. Analysis by fluorescence-activated cell sorter (FACS) showed biphasic expression of CD63 and granulophysin after thrombin stimulation of control but not Hermansky-Pudlak platelets. Anti-CD63 effectively blocked detection of the protein by anti-granulophysin using immunofluorescence, ELISA, immunoblotting, and FACS analysis. Amino-terminal sequencing over the first 37 amino acids revealed that granulophysin was homologous to CD63, melanoma antigen ME491, and pltgp40. These results suggest that granulophysin and CD63 are possibly identical proteins. This is the first report of a protein present in platelet dense granules, lysosomes, and melanocytes, but deficient in a patient with Hermansky-Pudlak syndrome.

Utilization of machine learning for prediction of post-traumatic stress: a re-examination of cortisol in the prediction and pathways to non-remitting PTSD.

To date, studies of biological risk factors have revealed inconsistent relationships with subsequent post-traumatic stress disorder (PTSD). The inconsistent signal may reflect the use of data analytic tools that are ill equipped for modeling the complex interactions between biological and environmental factors that underlay post-traumatic psychopathology. Further, using symptom-based diagnostic status as the group outcome overlooks the inherent heterogeneity of PTSD, potentially contributing to failures to replicate. To examine the potential yield of novel analytic tools, we reanalyzed data from a large longitudinal study of individuals identified following trauma in the general emergency room (ER) that failed to find a linear association between cortisol response to traumatic events and subsequent PTSD. First, latent growth mixture modeling empirically identified trajectories of post-traumatic symptoms, which then were used as the study outcome. Next, support vector machines with feature selection identified sets of features with stable predictive accuracy and built robust classifiers of trajectory membership (area under the receiver operator characteristic curve (AUC)=0.82 (95% confidence interval (CI)=0.80-0.85)) that combined clinical, neuroendocrine, psychophysiological and demographic information. Finally, graph induction algorithms revealed a unique path from childhood trauma via lower cortisol during ER admission, to non-remitting PTSD. Traditional general linear modeling methods then confirmed the newly revealed association, thereby delineating a specific target population for early endocrine interventions. Advanced computational approaches offer innovative ways for uncovering clinically significant, non-shared biological signals in heterogeneous samples.

Lack of beta 2-microglobulin on the surface of canine transmissible venereal tumor cells.

beta 2-Microglobulin (beta 2m) expression on the cell surface of the naturally occurring, allotransplantable canine transmissible venereal tumor (TVT) was investigated by use of indirect membrane immunofluorescence and radioimmunoassay. Two cell populations were identified in animal-derived, collagenase-disaggregated TVT cell suspensions. About 80% of the cells lacked surface beta 2m expression, whereas about 20% of the cells strongly reacted with anti-dog beta 2m serum. With the use of a cell separation technique, beta 2m-negative cells were demonstrated to carry TVT markers on their surface, whereas the beta 2m-positive cells did not express the tumor markers. The beta 2m-positive cells seemed, therefore, to be tumor-infiltrating host cells. These findings were supported by fluorescence staining studies of frozen sections of the TVT. The lack of beta 2m expression on the surface of TVT cells might explain the allotransplantability of this neoplasm, since beta 2m expression on the cell surface appeared to be obligatory for the expression of class I major histocompatibility complex antigens.

Physiologic responses to loud tones in Israeli patients with posttraumatic stress disorder.

Orbicularis oculi (eye blink) electromyogram, skin conductance, and heart rate responses to 15 consecutive 95-dB, 500-millisecond, 1000-Hz tones with 0-millisecond rise and fall times were measured in 14 patients with posttraumatic stress disorder, 14 patients with other anxiety disorders, 15 mentally healthy subjects with past traumatic experiences, and 19 mentally healthy subjects with no trauma history. The patients with posttraumatic stress disorder showed significantly larger skin conductance and heart rate responses and a trend toward larger electromyogram responses to the tones than every other group. These effects were not explained by subjective anxiety, resting physiologic arousal, physiologic arousal preceding the tone trials, or initial physiologic responsivity. The group with posttraumatic stress disorder was the only one that failed to show habituation of skin conductance responses.

A prospective study of heart rate response following trauma and the subsequent development of posttraumatic stress disorder.

BACKGROUND: Physiological arousal during traumatic events may trigger the neurobiological processes that lead to posttraumatic stress disorder (PTSD). This study prospectively examined the relationship between heart rate and blood pressure recorded immediately following a traumatic event and the subsequent development of PTSD. METHODS: Eighty-six trauma survivors who presented at the emergency department of a general hospital were followed up for 4 months. Heart rate and blood pressure were recorded on arrival at the emergency department. Heart rate, anxiety, depression, and PTSD symptoms were assessed 1 week, 1 month, and 4 months later. The clinician-administered PTSD scale defined PTSD status at 4 months. RESULTS: twenty subjects (23%) met PTSD diagnostic criteria at the 4-month assessment (PTSD group), and 66 (77%) did not (non-PTSD group). Subjects who developed PTSD had higher heart rates at the emergency department (95.5+/-13.9 vs 83.3+/-10.9 beats per minute, t=4.4, P<.001) and 1 week later (77.8+/-11.9 vs 72.0+/-9.5 beats per minute, t=2.25, P<.03), but not after 1 and 4 months. The groups did not differ in initial blood pressure measurement. Repeated-measures analysis of variance (ANOVA) for heart rate showed a significant group effect (P<.02), time effect (P<.001), and group x time interaction (P<.001). The time effect and group x time interaction remained significant when adjusted for sex, age, trauma severity, immediate response, and dissociation during the traumatic event. CONCLUSION: Elevated heart rate shortly after trauma is associated with the later development of PTSD.

The peroxisome proliferator-activated receptor alpha is a phosphoprotein: regulation by insulin.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily implicated in adipocyte differentiation. The observations that PPAR alpha is a regulator of hepatic lipid metabolism and that the insulin-sensitizing thiazolidinediones are ligands for PPAR gamma suggest that cross-talk might exist between insulin signaling and PPAR activity, possibly through insulin-induced PPAR phosphorylation. Immunoprecipitation of endogenous PPAR alpha from primary rat adipocytes prelabeled with [32P]-orthophosphate and pretreated for 2 h with vanadate and okadaic acid demonstrated for the first time that PPAR alpha is a phosphoprotein in vivo. Treatment with insulin induced a time-dependent increase in PPAR phosphorylation showing a 3-fold increase after 30 min. Insulin also increased the phosphorylation of human PPAR alpha expressed in CV-1 cells. These changes in phosphorylation were paralleled by enhanced transcriptional activity of PPAR alpha and gamma. Transfection studies in CV-1 cells and HepG2 cells revealed a nearly 2-fold increase of PPAR activity in the presence of insulin. In contrast, insulin had no effect on the transcriptional activity of transfected thyroid hormone receptor in CV-1 cells, suggesting a PPAR-specific effect. Thus, insulin stimulates PPAR alpha phosphorylation and enhances the transcriptional activity of PPAR, suggesting that the transcriptional activity of this nuclear hormone receptor might be modulated by insulin-mediated phosphorylation.

Predicting the development of posttraumatic stress disorder from the acute response to a traumatic event.

Posttraumatic stress disorder (PTSD) is a psychiatric condition that is directly precipitated by an event that threatens a person's life or physical integrity and that invokes a response of fear, helplessness, or horror. In recent years it has become clear that only a proportion of those exposed to fear-producing events develop or sustain PTSD. Thus, it seems that an important challenge is to elucidate aberrations in the normal fear response that might precipitate trauma-related psychiatric disorder. This paper summarizes the findings from recent studies that examined the acute and longer term biological response to traumatic stress in people appearing to the emergency room immediately following trauma exposure. In the aggregate, these studies have demonstrated increased heart rate and lower cortisol levels at the time of the traumatic event in those who have PTSD at a follow-up time compared to those who do not. In contrast, certain features associated with PTSD, such as intrusive symptoms and exaggerated startle responses, are only manifest weeks after the trauma. The findings suggest that the development of PTSD may be facilitated by an atypical biological response in the immediate aftermath of a traumatic event, which in turn leads to a maladaptive psychological state.

Vagal modulation of responses to mental challenge in posttraumatic stress disorder.

BACKGROUND: Studies of the autonomic nervous system in posttraumatic stress syndrome (PTSD) have focused on the sympathetic modulation of arousal and have neglected the parasympathetic contribution. This study addresses the parasympathetic control of heart rate in individuals who have survived traumatic events. METHODS: Twenty-nine survivors, 14 with current PTSD and 15 without, participated in the study. The groups were comparable with regard to age, type of trauma, time since the latest traumatic event, and lifetime exposure to traumatic events. Electrocardiograms were recorded during rest and an arithmetic task. Heart period, respiratory sinus arrhythmia (RSA), and the amplitude of the Traube-Hering-Mayer wave were quantified. RESULTS: The groups did not differ on resting measures. During the arithmetic task, the past trauma group showed a significant increase in RSA (p <.007), whereas the PTSD group did not. In the past trauma group only, RSA and heart period were highly correlated (r =.75), thereby suggesting that the response to challenge was under vagal control. CONCLUSIONS: Trauma survivors who develop PTSD differ from those who do not in the extent to which their heart rate response to challenge is controlled by vagal activity. Responses to challenge in PTSD may be mediated by nonvagal, possibly sympathetic mechanisms.

Psychophysiologic assessment of aversive conditioning in posttraumatic stress disorder.

BACKGROUND: The objective of this study was to evaluate the acquisition, generalization, and extinction of conditioned physiologic responses to aversive stimuli in posttraumatic stress disorder (PTSD). METHODS: Thirty-six PTSD patients, 20 individuals with past trauma and no current PTSD, and 30 mentally healthy individuals without exposure to major trauma underwent a differential aversive conditioning experiment. Bursts of 105 dB white noise were used as unconditioned stimuli (UCSs), and 35x24 mm slides of different colors served as either CS+ (paired) or CS- (unpaired) stimuli. Heart rate (HR) and nondominant palm skin conductance (SC) were measured at rest and between 1 and 4 sec following each CS presentation. RESULTS: The PTSD group showed higher levels of resting SC and resting HR, larger SC responses to the initial presentation of unpaired CSs, larger HR responses following paired CS+ stimuli, larger SC responses to unpaired CS- during acquisition and extinction, and larger SC and HR responses to CS+ during extinction. The group differences in responses to CS+ during extinction remained statistically significant after controlling for age, resting physiologic levels, and initial responsivity. CONCLUSIONS: PTSD is associated with elevated autonomic responses to both innocuous and aversive stimuli, with larger responses to unpaired cues and with reduced extinction of conditioned responses.

Alprazolam reduces response to loud tones in panic disorder but not in posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) and panic disorder (PD) share several clinical features, and theory postulates that phasic arousal is similarly dysregulated in both. The modulation of phasic arousal can be probed by measuring the effect of pharmacologic agents on auditory startle. METHODS: Eyeblink electromyogram, heart rate, and skin conductance (SC) responses to 15 consecutive presentations of 1000-Hz, 95-dB, zero rise-time pure tones were measured, before and during treatment with alprazolam, in 9 PTSD and 9 PD patients. Concurrent anxiety was assessed by the Hamilton Anxiety Rating Scale. RESULTS: The groups did not differ in initial psychometric and physiological measures. Significant decrease in anxiety was observed in both groups during treatment. A decrease in response probability and a decrease in the SC responses were observed in PD, but not in PTSD. CONCLUSIONS: The results may reflect a difference in the modulation of phasic arousal between the disorders. They may also express an impaired between-session habituation or contextual sensitization in PTSD.

Audiological evaluation of nonalcoholic, drug-free posttraumatic stress disorder patients.

Auditory functions of 32 Israeli soldiers with posttraumatic stress disorder (PTSD) were evaluated and compared with those of 32 matched controls without PTSD. The evaluation included peripheral auditory functions, tolerance to noise, and central auditory informational functions. Tolerance of intense auditory stimuli by PTSD patients was similar to that of controls. Significant differences were found between left and right ear central auditory functions in a subgroup of 13 PTSD subjects, but neither in other PTSD patients nor in controls. These findings are discussed in the light of previous research concerning abnormal responses to auditory stimulus in PTSD, hemispheric disconnection, alexithymia, and psychosomatic disorders.

Physiologic responses to loud tones in Israeli veterans of the 1973 Yom Kippur War.

Eyeblink and autonomic components of the acoustic startle response were evaluated in a community sample of Israeli veterans of the Yom Kippur war. Individuals were solicited by mail and telephone to participate in the study; they were not seeking treatment or compensation. Nineteen Israeli veterans with current posttraumatic stress disorder (PTSD) and 74 veterans without PTSD were exposed to 15 consecutive 95-dB, 500-msec, 1000-Hz tones with 0-msec rise and fall times, while orbicularis oculi electromyogram, skin conductance, and heart rate responses were measured. Individuals with PTSD produced larger averaged heart rate responses, and a slower decline in skin conductance responses, across the 15 tone presentations compared to non-PTSD subjects. There was no group difference in the magnitude of the averaged electromyogram response. Results of this study replicate previous findings of increased autonomic responses to loud tone stimuli in this disorder.

The hypouricemic effect of chlorprothixene.

The hypouricemic effect of chlorprothixene (Taractan), a major tranquilizer from the group of thioxanthenes, was evaluated in 30 psychiatric patients who took the drug as part of their regular treatment. Levels of serum uric acid, urea, and creatinine before, during, and after the treatment were measured, as well as creatinine clearance and uric acid clearance before and during the treatment. A uricosuric effect, resembling that of probenecid, was found that exerts itself in all the patients, regardless of age, sex, diagnosis, and associated drugs. The resulting hypouricemia starts as soon as 24 hours from the beginning of treatment, stabilizes within 10 days, and averages, at that time, 48% of the initial level. It is reversible within 10 days from the end of treatment.

The role of external heat load in triggering the neuroleptic malignant syndrome.

During a heat wave three patients developed neuroleptic malignant syndrome. The role of heat load in triggering this syndrome and possible mechanisms behind such a role are discussed. Data concerning the season of occurrence of neuroleptic malignant syndrome are reported.