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.

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.

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.

Development of an enzyme-linked immunosorbent assay and a beta-1 adrenergic receptor-based assay for monitoring the drug atenolol.

Two approaches for monitoring atenolol (ATL) were applied: an immunochemical assay and a competitive-binding assay, based on the interaction between ATL and its target receptor, ß1 adrenergic receptor (ß1AR). Polyclonal antibodies (Abs) for ATL were generated, and a highly specific microplate immunochemical assay, that is, an enzyme-linked immunosorbent assay (ELISA), for its detection was developed. The ATL ELISA exhibited I50 and limit of detection (I20) values of 0.15 ± 0.048 and 0.032 ± 0.016 ng/ml, respectively, and the Abs did not cross-react with any of the tested beta-blocker drugs. Furthermore, a human ß1AR (h-ß1AR) was stably expressed in Spodoptera frugiperda cells (Sf9). The receptor was employed to develop a competitive-binding assay that monitored binding of ATL in the presence of isoproteranol by quantification of secondary messenger, cyclic adenosine monophosphate (cAMP), levels in the transfected cells. The assay showed that the recombinant h-ß1AR was functional, could bind the agonistic ligand isoproterenol as well as the antagonist ATL, as indicated by a dose-dependent elevation of cAMP in the presence of isoproteranol, and decrease after ATL addition. The highly efficient and sensitive ELISA and the receptor assay represent two methods suitable for efficient and cost-effective large-scale, high-throughput monitoring of ATL in environmental, agricultural, and biological samples.

[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.

Conservative management of implantable cardioverter defibrillator-related endocarditis due to Bacillus spp.

Endocarditis is a devastating complication of implantable cardioverter-defibrillator (ICD) therapy. Partial or complete device removal has been advocated for the treatment of this condition although controlled data are lacking. We present a case of ICD-related endocarditis caused by Bacillus spp. that occurred following coronary angiography. To the best of our knowledge, Bacillus spp. has not been previously described in such context. Moreover, conservative treatment with device retention was successful (no recurrence during a 6-year follow-up). Conservative management may be attempted in selected cases of ICD-related endocarditis, especially, those involving low-virulence organisms and rapid response to antibiotic therapy. This case also suggests that coronary angiography may be associated with transient bacteremia and subsequent infection of indwelling cardiac devices.

Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors.

Trauma survivors show marked differences in the severity and persistence of post-traumatic stress disorder (PTSD) symptoms. Early symptoms subside in most, but persist as acute and chronic PTSD in a significant minority. The underlying molecular mechanisms or outcome predictors determining these differences are not known. Molecular markers for identifying any mental disorder are currently lacking. Gene expression profiling during the triggering and development of PTSD may be informative of its onset and course. We used oligonucleotide microarrays to measure peripheral blood mononuclear cell (PBMC) gene expression of trauma survivors at the emergency room and 4 months later. Gene expression signatures at both time points distinguished survivors who met DSM-IV diagnostic criteria for PTSD at 1 and 4 months, from those who met no PTSD criterion. Expression signatures at both time points correlated with the severity of each of the three PTSD symptom clusters assessed 4 months following exposure among all survivors. Results demonstrate a general reduction in PBMCs' expression of transcription activators among psychologically affected trauma survivors. Several differentiating genes were previously described as having a role in stress response. These findings provide initial evidence that peripheral gene expression signatures following trauma identify an evolving neuropsychiatric disorder and are informative of its key clinical features and outcome. Replications in larger samples, as well as studies focusing on specific markers within the signatures discovered, are warranted to confirm and extend the diagnostic utility and pathogenetic implications of our results.

Association between the dopamine transporter gene and posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a chronic anxiety disorder that follows exposure to extreme events. A large twin study of Vietnam veterans had demonstrated a significant genetic contribution to chronic PTSD upon exposure to combat.(1,2) The underlying genes, however, have not been described. Given previous findings of abnormal dopamine (DA) function in PTSD, and given the putative effect of dopamine neurotransmission in shaping the responses to stress in animals, this study examined the association of the dopamine transporter (DAT) SLC6A3 3' variable number tandem repeat (VNTR) polymorphism with PTSD. The study evaluated 102 chronic PTSD patients and 104 carefully-documented trauma survivors (TS) who did not develop PTSD. Significant excess of 9 repeat allele was observed among PTSD patients (43% vs 30.5% in TS controls; chi(2) = 6.3, df = 1, P = 0.012). An excess of 9 repeat homozygous genotype was also observed in PTSD (20.43% in PTSD vs 9.47% in TS controls; chi(2) = 6.11, df = 2, P < 0.047). These findings suggest that genetically determined changes in dopaminergic reactivity may contribute to the occurrence of PTSD among trauma survivors.

What is posttraumatic stress disorder?

Our understanding of posttraumatic stress disorder (PTSD) has increased significantly over the last 2 decades. Although the cause of the condition is usually easy to determine in individual patients, the symptoms of PTSD are diverse and a mixture of psychological processes are involved. This article presents a broad overview of PTSD, including its definition according to DSM-IV and ICD-10 diagnostic criteria, and its clinical course with reference to its association with depression and other mental disorders. The article also briefly reviews the assessment of patients and considers physiologic features such as responses to startle stimuli that appear to be useful in diagnosing PTSD and in differentiating it from other anxiety disorders and depression. Finally, a brief overview of the treatment of PTSD is given, including psychological and biological treatment options.

Longitudinal MRI study of hippocampal volume in trauma survivors with PTSD.

OBJECTIVE: The authors prospectively explored whether a reduction in the volume of the hippocampus occurs in recent trauma survivors who develop posttraumatic stress disorder (PTSD). METHOD: Thirty-seven survivors of traumatic events were assessed within a week of the traumatic event and 6 months later. The assessment included magnetic resonance imaging of the brain (including 124 coronal slices of 1.5-mm thickness), psychometric testing, and structured clinical interviews. The Clinician-Administered PTSD Scale conferred PTSD diagnoses at 6 months. RESULTS: Ten subjects (27%) had PTSD at 6 months. The subjects with PTSD did not differ from those without PTSD in hippocampal volume (right or left) at 1 week or 6 months. There was no reduction in hippocampal volume in the PTSD subjects between 1 week and 6 months. CONCLUSIONS: Smaller hippocampal volume is not a necessary risk factor for developing PTSD and does not occur within 6 months of expressing the disorder. This brain abnormality might occur in individuals with chronic or complicated PTSD.

Saccharomyces cerevisiae protein Pci8p and human protein eIF3e/Int-6 interact with the eIF3 core complex by binding to cognate eIF3b subunits.

Mammalian, plant, and Schizosaccharomyces pombe eukaryotic initiation factor-3 (eIF3) contains a protein homologous to the product of int-6 (eIF3e), a frequent integration site of mouse mammary tumor viruses. By contrast, Saccharomyces cerevisiae does not encode a protein closely related to eIF3e/Int-6. Here, we characterize a novel S. cerevisiae protein (Pci8p, Yil071cp) that contains a PCI (proteasome-COP9 signalosome-eIF3) domain conserved in eIF3e/Int-6. We show that both Pci8p and human eIF3e/Int-6 expressed in budding yeast interact with the yeast eIF3 complex in vivo and in vitro by binding to a discrete segment of its eIF3b subunit Prt1p and that human eIF3e/Int-6 interacts with the human eIF3b segment homologous to the Pci8p-binding site of yeast Prt1p. These results refine our understanding of subunit interactions in the eIF3 complex and suggest structural similarity between human eIF3e/Int-6 and yeast Pci8p. However, deletion of PCI8 had no discernible effect on cell growth or translation initiation as judged by polysome analysis, suggesting that Pci8p is not required for the essential function of eIF3 in translation initiation. Motivated by the involvement of Int-6 in transcriptional control, we investigated the effects of deleting PCI8 on the total mRNA expression profile by oligonucleotide microarray analysis and found reduced mRNA levels for a subset of heat shock proteins in the pci8Delta mutant. We discuss possible dual functions of Pci8p and Int-6 in transcriptional and translational control.

Multiple roles for the C-terminal domain of eIF5 in translation initiation complex assembly and GTPase activation.

eIF5 stimulates the GTPase activity of eIF2 bound to Met-tRNA(i)(Met), and its C-terminal domain (eIF5-CTD) bridges interaction between eIF2 and eIF3/eIF1 in a multifactor complex containing Met-tRNA(i)(Met). The tif5-7A mutation in eIF5-CTD, which destabilizes the multifactor complex in vivo, reduced the binding of Met-tRNA(i)(Met) and mRNA to 40S subunits in vitro. Interestingly, eIF5-CTD bound simultaneously to the eIF4G subunit of the cap-binding complex and the NIP1 subunit of eIF3. These interactions may enhance association of eIF4G with eIF3 to promote mRNA binding to the ribosome. In vivo, tif5-7A eliminated eIF5 as a stable component of the pre-initiation complex and led to accumulation of 48S complexes containing eIF2; thus, conversion of 48S to 80S complexes is the rate-limiting defect in this mutant. We propose that eIF5-CTD stimulates binding of Met-tRNA(i)(Met) and mRNA to 40S subunits through interactions with eIF2, eIF3 and eIF4G; however, its most important function is to anchor eIF5 to other components of the 48S complex in a manner required to couple GTP hydrolysis to AUG recognition during the scanning phase of initiation.

Posttraumatic stress disorder: diagnosis and epidemiology, comorbidity and social consequences, biology and treatment.

Epidemiological studies clearly indicate that posttraumatic stress disorder (PTSD) is becoming a major health concern worldwide even if still poorly recognized and not well treated. PTSD commonly co-occurs with other psychiatric disorders, and several symptoms overlap with major depressive disorders, anxiety disorders and substance abuse; this may contribute to diagnostic confusion and underdiagnosis. This anxiety disorder provokes significant occupational, psychiatric, medical and psychosocial disability, and its consequences are enormously costly, not only to the survivors and their families, but also to the health care system and society. Work impairment associated with PTSD is very similar to the amount of work impairment associated with major depression. The pathophysiology of PTSD is multifactorial and involves dysregulation of the serotonergic as well as the noradrenergic system. A rational therapeutic approach should normalize the specific psychobiological alterations associated with PTSD. This can be achieved through the use of antidepressant drugs, mainly of those that potentiate serotonergic mechanisms. Recent double-blind placebo-controlled studies report the efficacy of selective serotonin reuptake inhibitors. Several cognitive-behavioral and psychosocial treatments have also been reported to be efficacious and could be considered when treating PTSD patients.

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.

Triiodothyronine augmentation of selective serotonin reuptake inhibitors in posttraumatic stress disorder.

BACKGROUND: There is considerable comorbidity of major depression and posttraumatic stress disorder (PTSD), and antidepressants have been reported to be effective in treating PTSD. Addition of triiodothyronine (T3) to ongoing antidepressant treatment is considered an effective augmentation strategy in refractory depression. We report the effect of T3 augmentation of antidepressants in patients with PTSD. METHOD: T3 (25 microg/day) was added to treatment with a selective serotonin reuptake inhibitor (SSRI) (paroxetine or fluoxetine, 20 mg/day for at least 4 weeks and 40 mg/day for a further 4 weeks) of 5 patients who fulfilled DSM-IV criteria for PTSD but not for major depressive disorder (although all patients had significant depressive symptoms). The Clinician-Administered PTSD Scale, the 21-item Hamilton Rating Scale for Depression, and the Clinical Global Impressions-Severity of Illness scale were administered every 2 weeks, and self-assessments were performed with a 100 mm visual analog mood scale. RESULTS: In 4 of the 5 patients, partial clinical improvement was observed with SSRI treatment at a daily dose of 20 mg with little further improvement when the dose was raised to 40 mg/day. This improvement was substantially enhanced by the addition of T3. Improvement was most striking on the Hamilton Rating Scale for Depression. CONCLUSION: T3 augmentation of SSRI treatment may be of therapeutic benefit in patients with PTSD, particularly those with depressive symptoms. Larger samples and controlled studies are needed in order to confirm this observation.