Internet-based emotion regulation training aimed at reducing violent revictimization and depressive symptoms in victimized depressed patients: Results of a randomized controlled trial.

BACKGROUND: Depressed patients who have become victim of violence are prone to revictimization. However, no evidence-based interventions aimed at reducing revictimization in this group exist. METHODS: This multicenter randomized controlled trial evaluated the effectiveness of an internet-based emotion regulation training (iERT) added to TAU in reducing revictimization, emotion dysregulation, and depressive symptoms in recently victimized, depressed patients compared to TAU alone. Adult outpatients (N = 153) with a depressive disorder who had experienced threat, physical assault, or sexual assault within the previous three years were randomly allocated to TAU+iERT (n = 74) or TAU (n = 79). TAU involved psychotherapy (mainly cognitive behavioral therapy [77.8 %]). iERT comprised six guided online sessions focused on the acquisition of adaptive emotion regulation skills. The primary outcome measure was the number of revictimization incidents at 12 months after baseline, measured with the Safety Monitor. Analyses were performed according to the intention-to-treat principle. RESULTS: Both groups showed a large decrease in victimization incidents. Mixed-model negative binomial regression analyses showed that TAU+iERT was not effective in reducing revictimization compared to TAU (IRR = 0.97; 95%CI = 0.64,1.46; p = .886). Linear mixed-model analyses demonstrated that TAU+iERT yielded a larger reduction of emotion dysregulation (B = -7.217; p = .046; Cohens d = 0.33), but not depressive symptoms (B = -1.041; p = .607) than TAU. LIMITATIONS: The study was underpowered to detect small treatment effects. Additionally, uptake of iERT was quite low. CONCLUSIONS: Although TAU+iERT resulted in a larger decrease of emotion dysregulation than TAU alone, it was not effective in reducing revictimization and depressive symptoms. Patients' revictimization risk substantially decreased during psychotherapy.

Violent victimization and revictimization in patients with depressive disorders: context characteristics, disclosure rates, and gender differences.

BACKGROUND: Depressed patients are prone to violent victimization, and patients who were victimized once are at increased risk to fall victim to violence again. However, knowledge on the context of victimization in depressed patients is lacking, and research identifying targets for prevention is urgently needed. METHODS: This cross-sectional study explored context characteristics, disclosure rates and gender differences regarding violent victimization in 153 recently victimized depressed patients. Additionally, 12-month prevalence rates of repeat threat, physical assault, and sexual assault were examined, and gender differences were investigated using t-tests, Chi-square tests, and Fisher's exact tests. Furthermore, logistic regression analyses were used to identify factors associated with repeat victimization. RESULTS: Overall, depressed men were most often victimized by a stranger in public, and women by their partner or ex-partner at home. Regarding sexual assault, no gender differences could be examined. Patients were sexually assaulted most often by an acquaintance (50.0%) or stranger (27.8%). In all patients, the most recent incidents of threat (67.6%) and physical assault (80.0%) were often preceded by a conflict, and only a minority had been intoxicated prior to the assault. Notably, less than half of patients had disclosed their recent experience of threat (40.6%) and physical assault (47.1%) to their mental health caregiver. For sexual assault, this was only 20%. Less than one third of patients had reported their recent experience of threat (27.9%), physical assault (30.0%) and sexual assault (11.1%) to the police. 48.4% of patients had been victimized repeatedly in the past year, with no gender differences found. Only depressive symptoms and unemployment were univariately associated with repeat victimization, but not in the multiple model. CONCLUSIONS: The high prevalence of repeat victimization in depressed patients and their low disclosure rates stress the need to implement routine enquiry of victimization in mental health care, and to develop preventive interventions accounting for specific needs of men and women.

[The underrepresentation of complex patient groups in scientific research: ethical considerations]. / De ondervertegenwoordiging van complexe patiëntengroepen in wetenschappelijk onderzoek: ethische overwegingen.

BACKGROUND: Subgroups of patients with severe mental illness are underrepresented in scientific research. One of the possible causes is the fact that in these patient groups barriers may exist to the giving of competent informed consent. AIM: Describing the ethical dilemmas that may occur when conducting research with these patient groups. METHOD: We present an overview of the Dutch legislation and regulation concerning participation in scientific research, and discuss the ethical dilemmas that arise in the mentioned patient groups. We present four directions for solutions. RESULTS: In research with these patient groups more attention is needed for the explicit assessment and enhancement of competence. For the subgroup that is persistently incompetent, the possibilities of doing research with existing patient data without informed consent, need further exploration. CONCLUSION: Further legislative development is needed for research with patients with severe mental illness who are persistently incompetent. Herein, it is crucial to involve ethicists and organizations representing patients' and relatives' perspectives.

[Exchange of information between psychiatrist and pharmacist concerning uncollected medication]. / Informatie-uitwisseling tussen psychiater en apotheker over niet-opgehaalde medicatie.

Background Non- compliance with drug regimens has a negative effect on symptomatology and is the largest predictor of relapse in people with Severe Psychiatric Disorder (EPA). When care providers are informed in good time that medication has not been collected and can act on it, compliance can be increased. Aim Assessment of usefulness and feasibility of a system for the Signaling and Reporting by Pharmacists of Uncollected Medication for people with an EPA (Dutch: 'SMANOM-EPA') within the current legal context. Method The package of requirements was drawn up on the basis of questionnaires and telephone interviews with psychiatrists and pharmacists and focus group meetings with patients and significant others. Lawyers and ICT professionals were consulted to formulate the legal and technical preconditions. Results All parties involved considered SMANOM-EPA to be useful. The administrative burden was a determining factor for the feasibility and transparency was an important precondition. The exchange of information could take place securely with existing technology, despite the variation in prescribing and issuing systems. However, opinions were divided as to whether informing and documenting is sufficient or whether consent is necessary. Conclusion The GDPR and the WBGO safeguard patients' rights regarding the use of personal data. Uncertainty about the legal framework and technological possibilities add to the complexity of innovations to promote the exchange of information between practitioners, while the added value is seen by those involved and in comparable innovations. Tijdschrift voor Psychiatrie 63(2021)1, 32-38.

Detailed immune monitoring of a pregnant woman with critical Covid-19.

A primigravid woman with Covid-19 related respiratory insufficiency was admitted into a tertiary Intensive Care Unit at 23 3/7 weeks' gestation. Highly sensitive flow cytometry of peripheral leukocytes indicated significantly suppressed naïve T- and B-cell compartments. The suppressed immune cell responses led us keep the initially started administration of corticosteroids for fetal and maternal indication at a low dose. After three weeks her B-cell response peaked, SARS-CoV-2 was cleared and clinical improvement ensued a week later. At 28 weeks' gestation, a son of 1570 g was born by cesarean section. She was extubated two days postpartum and discharged from hospital 5.5 weeks postpartum.

[Victimization among dual diagnosis patients and effectiveness of the sos training]. / Victimisatie van patiënten met een dubbele diagnose en effectiviteit van de groepsinterventie sos training.

BACKGROUND: Patients with a co-occurring substance use disorder and other mental disorder (dual diagnosis) are at increased risk of victimization: to become victims of for instance physical abuse, sexual abuse, and property crimes.
AIM: To examine the effectiveness of the sos training: a new group-based intervention to improve resilience of dual diagnosis patients and thereby reduce their risk of victimization.
METHOD: A randomized controlled trial was conducted in dual diagnosis patients, with a 14-month follow-up period. Patients were randomized to receive either care as usual (n = 125), or care as usual plus sos training (n =125). The primary outcome measure was defined as treatment response for victimization (yes/no), with 'yes' defined as at least a 50% reduction in the number of past-year victimization incidents at 14-month follow-up compared to baseline.
RESULTS: Significantly more participants in the experimental group achieved positive treatment response for victimization (68%) compared to the control group (54%).
CONCLUSION: Adding sos training to care as usual in dual diagnosis patients is more effective in reducing victimization compared to care as usual alone. The sos training can be implemented in addiction-psychiatry services to prevent future victimization in these patients.

Mental disorders and the risk of adult violent and psychological victimisation: a prospective, population-based study.

AIMS: Psychiatric patients are at increased risk to become victim of violence. It remains unknown whether subjects of the general population with mental disorders are at risk of victimisation as well. In addition, it remains unclear whether the risk of victimisation differs across specific disorders. This study aimed to determine whether a broad range of mood, anxiety and substance use disorders at baseline predict adult violent (physical and/or sexual) and psychological victimisation at 3-year follow-up, also after adjustment for childhood trauma. Furthermore, this study aimed to examine whether specific types of childhood trauma predict violent and psychological victimisation at follow-up, after adjustment for mental disorder. Finally, this study aimed to examine whether the co-occurrence of childhood trauma and any baseline mental disorder leads to an incrementally increased risk of future victimisation. METHODS: Data were derived from the first two waves of the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2): a psychiatric epidemiological cohort study among a nationally representative adult population. Mental disorders were assessed using the Composite International Diagnostic Interview version 3.0. Longitudinal associations between 12 mental disorders at baseline and violent and psychological victimisation at 3-year follow-up (n = 5303) were studied using logistic regression analyses, with adjustment for sociodemographic characteristics and childhood trauma. Furthermore, the moderating effect of childhood trauma on these associations was examined. RESULTS: Associations with victimisation varied considerably across specific mental disorders. Only alcohol dependence predicted both violent and psychological victimisation after adjustment for sociodemographic characteristics and childhood trauma. Depression, panic disorder, social phobia, generalised anxiety disorder and alcohol dependence predicted subsequent psychological victimisation in the fully adjusted models. All types of childhood trauma independently predicted violent and psychological victimisation after adjustment for any mental disorder. The presence of any childhood trauma moderated the association between any anxiety disorder and psychological victimisation, whereas no interaction between mental disorder and childhood trauma on violent victimisation existed. CONCLUSIONS: The current study shows that members of the general population with mental disorders are at increased risk of future victimisation. However, the associations with violent and psychological victimisation vary considerably across specific disorders. Clinicians should be aware of the increased risk of violent and psychological victimisation in individuals with these mental disorders - especially those with alcohol dependence - and individuals with a history of childhood trauma. Violence prevention programmes should be developed for people at risk. These programmes should not only address violent victimisation, but also psychological victimisation.

Prevalence and predictors of violent victimization in remitted patients with recurrent depression.

BACKGROUND: Depressed patients are at increased risk to fall victim to a violent crime compared to the general population. It remains unknown whether their increased risk persists after remission. This study compared victimization rates of remitted patients with both a random general population sample and a group of currently depressed patients. Furthermore, this study aimed to identify predictors of future violent victimization. METHODS: In this longitudinal study conducted in the Netherlands, 12-month prevalence rates of sexual assaults, physical assaults, and threats were assessed with the Safety Monitor in 140 currently remitted patients with recurrent depression, and compared to those of a weighted general population sample (N = 9.175) and a weighted sample of currently depressed outpatients (N = 102) using Chi-square tests. Logistic regression analyses were performed to identify baseline predictors of future victimization. RESULTS: The prevalence of violent victimization did not differ between remitted patients and the general population (12.1 vs. 11.7%). Remitted patients were significantly less likely to have been victimized over the past 12 months than currently depressed patients (12.1 vs. 35.5%). In remitted patients, living alone and low sense of mastery at baseline predicted future violent victimization. However, when combined in a multiple model, only living alone was independently associated with violent victimization (χ2 = 16.725, df = 2, p < .001, R2 = 0.221). LIMITATIONS: Our comparison of victimization rates across samples was cross-sectional. CONCLUSIONS: Since the increased risk of victimization appears to be specific for the acute depressive state, preventive interventions should target victimization in currently depressed patients. TRIAL REGISTRATION: Netherlands Trial Register (NTR): 2599.

The role of affect in predicting depressive symptomatology in remitted recurrently depressed patients.

BACKGROUND: Major depressive disorder is an emotional disorder. It is important to improve our understanding of the role of affect in relapse/recurrence of depression. Therefore, this study examines whether affect plays a role in prospectively predicting depressive symptomatology and if there are indications for emotional scarring as a consequence of undergoing depressive episodes. METHODS: In 107 patients remitted from recurrent depression affect was examined in predicting depressive symptomatology as measured with the Inventory of Depressive Symptomatology - Self Report. Affect was measured with the Positive and Negative Affect Schedule and with a one item Visual Analogue Mood Scale. Indication of emotional scarring was examined by comparing number of previous depressive episodes to levels of affect. RESULTS: Less positive affect as assessed after remission predicted increased depressive symptomatology six months later, even after we controlled for baseline symptomatology. Negative affect also predicted depressive symptomatology six months later, but not after controlling for baseline depressive symptomatology. No relationship was found between affect and number of previous episodes. LIMITATIONS: All participants in this study had two or more previous depressive episodes and received CBT during the acute phase of their depression. The instruments that measured mood and affect were administered within 4 weeks of each other. CONCLUSIONS: Positive affect and negative affect as assessed after remission in recurrent depression can predict depressive symptomatology. Especially positive affect seems to play an independent role in predicting depressive symptomatology. Directly targeting positive affect in relapse prevention during remission might be a way to enhance treatment effects.

[The aftermath of the reduction in inpatient care and treatment II: cross-sectional study relating to the health, the need for care, the quality of life, social functioning and the integration in society of chronic mental patients in Amsterdam]. / Na de extramuralisering. II. Een crosssectionele studie naar psychisch en sociaal functioneren en kwaliteit van leven van een steekproef van chronische psychiatrische patiënten in de Amsterdamse ggz.

BACKGROUND: The move from less hospital care to more community-based care was expected to have positive results for long-term mental patients. It was believed that independent living would improve the quality of life and promote better social functioning and better integration into society. The basic idea was that the needs of patients would be better served by outpatient care. AIM: To map particulars relating to illness symptoms, functioning, care needs, quality of life, extent and features of the social network and social integration of a group of long-term psychiatric patients in Amsterdam 15 years after the closure of the Santpoort psychiatric hospital. METHOD: Interviews and questionnaires were used to obtain information from a stratified sample of long-term mental patients in the care of the mental health organisations in Amsterdam. RESULTS: 323 patients and those who were treating them were interviewed. Most group members were fairly elderly and one-third suffered from schizophrenia. More than half of the group had long-term psychiatric problems. Most of the patients were in poor health, half of the group had somatic symptoms and a quarter abused alcohol or drugs. Patients and doctors had varying views on whether patients’ needs had been met. Patients had few social contacts. About one-third of these social contacts were with fellow-patients. Patients living independently caused few or no problems in the city. However, these patients were more often victim of discrimination, social exclusion and criminality. CONCLUSION: Many patients with long-term mental illness considered their current quality of life to be reasonably good and were satisfied with the health care they received. However, the limited number of social contacts, inadequate integration into society and the poor health of many patients are matters that still give cause for concern.

Are long-term psychiatric patients causing more crisis consultations outside office hours in mental health care?

BACKGROUND: As well as an improvement in community services, the de-institutionalization of patients receiving long-term psychiatric care can lead to marginally staffed mental health services, more homelessness, rising admission rates and more people in prison cells. It is assumed that an imbalance between community and hospital care for chronic patients puts pressure on crisis services. AIMS: In this study, the central question is whether patients receiving long-term psychiatric care in Amsterdam do indeed put pressure on the city's emergency mental health services. We compare the pressure exerted by this group with the pressure resulting from the use of these services by all registered patients. METHODS: Data were taken from the client registration systems of three mental health organizations in Amsterdam in the period from 2000 to 2004. Inclusion criteria for long-term psychiatric patients were age above 19 years and uninterrupted receipt of mental health care for a minimum of two successive years. RESULTS: Annually, 6%-8% of all non-long-term patients experienced a crisis outside office hours in the period under investigation; this was 4%-6% for long-term patients. The non-long-term patients accounted for 83% of crisis contacts outside office hours over the entire study period, with long-term patients accounting for 17%. CONCLUSIONS: The assumption that crises are more prevalent in long-term patients in the community seems to be an example of stigmatization rather than an observation based on fact.

[The aftermath of the reduction in inpatient care and treatment; a retrospective study that considers the extent to which a group of chronic psychiatric patients made use of the Amsterdam mental health services]. / Na de extramuralisering; een retrospectief onderzoek naar omvang en zorggebruik van de groep chronische patiënten in de Amsterdamse ggz.

BACKGROUND: The move towards less hospital care and more community care for psychiatric patients began in the eighties. Chronic patients possibly have not really benefited from the new procedures. AIM: To find out whether chronic psychiatric patients in Amsterdam were receiving adequate care and made good use of the available psychiatric services. METHOD: We amalgamated the registration details of three mental health care institutions in Amsterdam over the period 1-1-2000 to 1-1-2005. RESULTS: In 2005 4576 patients met the criteria for chronic mental illness. In five years, the number of patients in mental health care had risen by 50%. Most of these patients had received care via specialised programmes. 38% of chronic patients had no access to specialised programmes, many of which had waiting lists. Only 6.5% of chronic patients received long-term inpatient care. Not many long-term psychiatric patients used the acute psychiatric services. Each year only 10% of long-term psychiatric patients were admitted to a psychiatric hospital. If admitted, they spent a much longer time in hospital. The average number of days spent in hospital rose from 86 in 2000 to 131 in 2004. Crisis contacts increased in line with the increase in the numbers of chronic patients in care, but these crisis contacts were registered mainly with the patient treatment team and not with the municipal acute psychiatric service. CONCLUSION: Only a small proportion of long-term psychiatric patients make use of the acute psychiatric services.

Effect of wearing an activity monitor on the amount of daily manual wheelchair propulsion in persons with spinal cord injury.

STUDY DESIGN: An experimental study. OBJECTIVES: To assess the effect of reactivity related to wearing a multi-sensor activity monitor (AM) on the amount of manual wheelchair propulsion during daily life in wheelchair-bound persons with spinal cord injury (SCI). In addition, to establish the subjectively experienced burden of wearing the AM. SETTING: Rehabilitation centre and home-based study. METHODS: In 10 persons with SCI, during a 7-day period, the daily amount of manual wheelchair propulsion was measured by means of a rotation counter. During this period, an AM was worn for 1 day (AM+ day) by the participants. Experienced burden was measured by a questionnaire based on visual analogue scale scores. RESULTS: The overall median of the number of rotations per minute was 1.38 (range 0.63-1.83). No significant difference was found in the amount of daily manual wheelchair propulsion between AM+ and AM- days (P=0.33, median difference: -0.06 rotations per minute). Experienced burden was not different between subgroups that differed in reactivity. CONCLUSION: The results seem to indicate that wearing the AM of this study does not systematically influence the amount of daily manual wheelchair propulsion. Although low to moderate burden was experienced when wearing the AM, this does not seem to affect the amount of manual wheelchair propulsion.

The role of the ubiquitination machinery in dislocation and degradation of endoplasmic reticulum proteins.

Ubiquitination is essential for the dislocation and degradation of proteins from the endoplasmic reticulum (ER). How exactly this is regulated is unknown at present. This review provides an overview of ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s) with a role in the degradation of ER proteins. Their structure and functions are described, as well as their mutual interactions. Substrate specificity and functional redundancy of E3 ligases are discussed, and other components of the ER degradation machinery that may associate with the ubiquitination system are reviewed.

The HCMV gene products US2 and US11 target MHC class I molecules for degradation in the cytosol.

Over millions of years of coevolution with their hosts, viruses have developed highly effective strategies to elude the host immune system. The degradation of major histocompatibility complex (MHC) class I heavy chains by human cytomegalovirus (HCMV) is an example of this. Two HCMV proteins, US2 and US11, target newly synthesized MHC class I heavy chains for destruction via a pathway that involves ubiquitin-dependent retrograde transport, or "dislocation", of the heavy chains from the ER to the cytosol, where the proteins are degraded by proteasomes. In this review, US2- and US11-mediated degradation of MHC class I heavy chains is discussed in relation to data concerning the degradation of other ER luminal proteins. A new, unified model for translocon-facilitated dislocation and degradation of MHC class I heavy chains is presented.

Ubiquitination is essential for human cytomegalovirus US11-mediated dislocation of MHC class I molecules from the endoplasmic reticulum to the cytosol.

Human cytomegalovirus encodes two glycoproteins, US2 and US11, which cause rapid degradation of MHC class I molecules, thus preventing recognition of virus-infected cells by the immune system. This degradation process involves retrograde transport or 'dislocation' of MHC class I molecules from the endoplasmic reticulum (ER) to the cytosol, where they are deglycosylated by an N-glycanase and degraded by the proteasome. At present it is unknown whether ubiquitination is required for US2- and US11-mediated dislocation and degradation of MHC class I molecules. Here, we show that in E36ts20 hamster cells, which contain a temperature-sensitive mutation in the E1 ubiquitin-activating enzyme, US11-mediated degradation of MHC class I molecules is strongly impaired at the non-permissive temperature, indicating the necessity for ubiquitination in this process. We next addressed the question of whether ubiquitination is a condition for the retrograde movement of MHC class I molecules from the ER to the cytosol, or whether ubiquitination is merely required for recognition of dislocated MHC class I molecules by the proteasome. In the absence of a functional ubiquitin system, complexes of US11 and MHC class I molecules accumulate in the ER. In this state the membrane topology of MHC class I molecules does not significantly change, as judged from proteinase K digestions. Thus the results indicate that a functional ubiquitin system is essential for dislocation of MHC class I molecules from the ER to the cytosol.

Cisapride associated with QTc prolongation in very low birth weight preterm infants.

OBJECTIVE: No systematic study has been performed to evaluate the effect of cisapride on the QT interval in premature infants. Cisapride, which has recently been withdrawn by the Food and Drug Administration and is no longer an approved therapy, was commonly used for preterm infant care to improve the advance of enteral feedings and to reduce reflux and associated apnea. Our aim was to evaluate the effect of recommended doses of cisapride on the QT interval in this population. STUDY DESIGN: Prospective blinded evaluation of electrocardiogram for QT, JT, QTc, and JTc measurements in 25 preterm infants before and after cisapride administration. RESULTS: Twelve of 25 infants (48%) developed repolarization abnormalities with cisapride administration: 32% of the infants (8/25) studied had QTc prolongation (>/=0.450 seconds), whereas 10/25 had JTc prolongation (>/=0.360 seconds). Preterm infants <32 weeks significantly prolonged their QTc interval from 0.41 +/- 0.02 to 0.44 +/- 0.02. The QTc and/or JTc was prolonged in 54% of infants receiving 0.1 mg/kg/dose and 42% receiving 0.2 mg/kg/dose. CONCLUSIONS: The QTc and JTc interval significantly prolonged in preterm infants <32 weeks on the recommended dose of cisapride therapy. A QTc >/=0.450 seconds developed in 32% of infants treated with cisapride, whereas the JTc prolonged in 40%. A significant percentage of infants (54%) developed prolonged QTc intervals at a dose of 0.1 mg/kg/dose. From these data we conclude that there is a higher risk of prolongation of the QTc interval and risk of arrhythmias with greater prematurity.

Cisapride decreases gastroesophageal reflux in preterm infants.

OBJECTIVE: Gastrointestinal prokinetic agents, such as cisapride, are commonly used in pediatric practice to improve gastric emptying, to decrease emesis, to improve lower esophageal sphincter tone, and to improve irritability and feeding aversion associated with gastroesophageal reflux (GER). Although cisapride seems to be effective in infants from 2 months to 14 years old, data for younger and preterm infants are not available. Whether reflux is a significant cause of reflex apnea or feeding intolerance in the preterm infant is controversial. The objective of this 1-year prospective study, started in 1998, was to determine the efficacy of cisapride for treatment of reflux and reflux-associated apnea (RAAP) in preterm infants. Before this study, the diagnosis of reflux was often made clinically and the effect of therapy on reflux or the decision to increase the dose of cisapride was made empirically. The clinical bias was that persistent apnea, not responding to caffeine, was caused by GER. We reasoned that a systematic approach to the diagnosis and treatment of reflux would improve the care of preterm infants and reduce the risk of toxicity, especially if an increased dose of cisapride showed no improvement in reflux or apnea. STUDY DESIGN: Twenty-four preterm infants (24-36 weeks' gestational age) had clinical apnea/pH studies when they were referred by the attending neonatologist for suspected GER. These infants were born at 28.8 +/- 3.1 weeks with birth weight of 1169 +/- 387 g (range: 631-2263 g). Each infant was studied before and 8 days after starting cisapride treatment. Cisapride dose was 0.09 to 0.25 mg/kg every 6 hours enterally. Treatment decisions regarding dose of cisapride were the responsibility of the attending neonatologist. The pH was recorded continuously for 24 hours at 0.25 Hz and was analyzed using EsopHogram software. A single sensor pH catheter was inserted to ~2 cm above the esophageal gastric junction. GER was defined as a drop in esophageal pH below 4.0 for a least 5 seconds, or pathologic GER was defined as a reflux index (RI) >2 standard deviation (SD) from the mean based on published norms for term infants. The following parameters were calculated from the pH recording: number of reflux events per 24 hours, duration of the longest episode, number of episodes >5 minutes per 24 hours, and RI, ie, percentage of time with pH <4.0. Each study had a combined time-lapse video recording and multichannel digital recording. Recorded parameters were: continuous pulse oximetry, electrocardiogram, respiratory effort (piezo sensor), and airflow (temperature sensor at nostrils and mouth). The recording was scored for central apneas of 10 to 14 seconds and >/=15 seconds (prolonged) and >/=10 seconds for obstructive and mixed apneas. RAAP was scored when an apnea (irrespective of the type) occurred within 1 minute of a GER event. Baseline, after cisapride, and follow-up electrocardiograms were performed because of concern about prolonged QTc and cardiac arrhythmias. The infants were 35.6 +/- 4.5 weeks postconceptional age when first studied. Twelve infants (mean birth weight: 1821 +/- 749 g; gestational age: 32 +/- 2 weeks; postconceptional age: 35.6 +/- 2.6 weeks) were identified retrospectively as controls because their baseline GER parameters were within the normal range using Vandenplas' criteria. RESULTS: Overall, cisapride treatment significantly improved the RI from 16.6 +/- 15.2 to 9.1 +/- 8.4 SD. The number of reflux episodes >/=5 minutes was reduced from 7.1 +/- 5.8 to 4.3 +/- 4.4 SD. No significant effect was seen on the total number of refluxes (/24 hours). Eight infants (33%) had no decrease in the RI after a week of treatment. Three of these infants improved after cisapride dose was increased from 0.09 to 0.25 mg/kg/dose every 6 hours. Although 0.09 mg/kg/day is the minimum effective dose, 67% of our infants did respond to this low dose. Cisapride was discontinued in 3 infants because of prolonged QTc >/=0.450 seconds (0.473 in 1 and 0.470 in 2). More data about the effect of cisapride on QTc interval are reported in Pediatrics in a separate article. Only 1 infant showed no improvement with increased dose. Caffeine treatment had no effect on the baseline or follow-up GER values. Although apnea indexes for central and obstructive apnea were similar before and after cisapride, mixed apnea was less during treatment. There was a significant decrease (0.32 +/- 0.40 to 0.12 +/- 0.17/hour) in RAAP when the one infant who had increased reflux on increased dose of cisapride was excluded as an outlier. The statistical difference, before and after cisapride, for the group is significant with the outlier omitted. The clinical significance is unclear because ~50% of the infants had minimal changes in their apnea indexes. Furthermore, ~40% of infants did not have RAAP. (ABSTRACT TRUNCATED)

Tomato spotted wilt virus glycoproteins exhibit trafficking and localization signals that are functional in mammalian cells.

The glycoprotein precursor (G1/G2) gene of tomato spotted wilt virus (TSWV) was expressed in BHK cells using the Semliki Forest virus expression system. The results reveal that in this cell system, the precursor is efficiently cleaved and the resulting G1 and G2 glycoproteins are transported from the endoplasmic reticulum (ER) to the Golgi complex, where they are retained, a process that could be blocked by tunicamycin. Expression of G2 alone resulted in transport to and retention in the Golgi complex, albeit less efficient, suggesting that G2 contains a Golgi retention signal. G1 alone was retained in the ER, irrespective of whether it contained the precursor's signal sequence or its own N-terminal hydrophobic sequence. Coexpression of G1 and G2 from separate gene constructs resulted in rescue of efficient G1 transport, as the proteins coaccumulated in the Golgi complex, indicating that their interaction is essential for proper targeting to this organelle. The results demonstrate that transport and targeting of the plant TSWV glycoproteins in mammalian BHK cells are strikingly similar to those of animal-infecting bunyavirus glycoproteins in mammalian cells. The observations are likely to reflect the dual tropism of TSWV, which replicates both in its plant host and in its animal (thrips) vector.