Smoking associated with reduced odds of Sjögren's syndrome among rheumatoid arthritis patients.

OBJECTIVE: The objective of this medical record review study is to define the association between smoking and SjÓ§gren's syndrome (SS) in a large rheumatoid arthritis (RA) cohort. METHODS: Electronic health records from a population-based cohort were screened for RA eligibility between 2005 and 2018. Inclusion criteria were age ≥ 18 years, two or more RA diagnoses, including two diagnoses by a rheumatologist, or positive rheumatoid factor or anti-cyclic citrullinated peptide (anti-CCP) antibody. The independent variable, smoking status, was defined as never, current, or past. The outcome, SS, was defined by two or more ICD-9 codes. Multivariable logistic regression was performed to determine odds ratios (ORs) of SS adjusted for age, sex, and race. RESULTS: Among 1861 patients with RA identified for cohort inclusion, 1296 had a reported smoking status. Current smokers were younger and less likely to be female than never smokers. The adjusted OR of current compared to never smokers was negatively associated with SS [OR 0.20, 95% confidence interval (CI) 0.06-0.65]. Female sex and age were associated with SS (OR 2.70, 95% CI 1.18-6.14; OR 3.75, 95% CI 1.23-11.4). CONCLUSION: We report that RA patients who currently smoke had 80% lower odds of SS. Age had a 3.7-fold association and female sex a 2.7-fold association with SS among RA patients. Our data suggest a negative correlation between current smoking and prevalent SS among RA patients. Prospective studies examining pack-year relationships or smoking cessation could further examine risk reduction and causality to follow-up our cross-sectional observational study.

A splicing-regulatory polymorphism in DRD2 disrupts ZRANB2 binding, impairs cognitive functioning and increases risk for schizophrenia in six Han Chinese samples.

The rs1076560 polymorphism of DRD2 (encoding dopamine receptor D2) is associated with alternative splicing and cognitive functioning; however, a mechanistic relationship to schizophrenia has not been shown. Here, we demonstrate that rs1076560(T) imparts a small but reliable risk for schizophrenia in a sample of 616 affected families and five independent replication samples totaling 4017 affected and 4704 unaffected individuals (odds ratio=1.1; P=0.004). rs1076560(T) was associated with impaired verbal fluency and comprehension in schizophrenia but improved performance among healthy comparison subjects. rs1076560(T) also associated with lower D2 short isoform expression in postmortem brain. rs1076560(T) disrupted a binding site for the splicing factor ZRANB2, diminished binding affinity between DRD2 pre-mRNA and ZRANB2 and abolished the ability of ZRANB2 to modulate short:long isoform-expression ratios of DRD2 minigenes in cell culture. Collectively, this work implicates rs1076560(T) as one possible risk factor for schizophrenia in the Han Chinese population, and suggests molecular mechanisms by which it may exert such influence.

Historical comparisons reveal altered competitive interactions in a guild of crustose coralline algae.

As the ocean environment changes over time, a paucity of long-term data sets and historical comparisons limits the exploration of community dynamics over time in natural systems. Here, we used a long-term experimental data set to present evidence for a reversal of competitive dominance within a group of crustose coralline algae (CCA) from the 1980s to present time in the northeast Pacific Ocean. CCA are cosmopolitan species distributed globally, and dominant space holders in intertidal and subtidal systems. Competition experiments showed a markedly lower competitive ability of the previous competitively dominant species and a decreased response of competitive dynamics to grazer presence. Competitive networks obtained from survey data showed concordance between the 1980s and 2013, yet also revealed reductions in interaction strengths across the assemblage. We discuss the potential role of environmental change, including ocean acidification, in altered ecological dynamics in this system.

Unchanged frequency and decreasing magnitude of outbursts from ice-dammed lakes in Alaska.

Glacial lakes can form and grow due to glacial retreat, and rapid lake drainage can produce destructive floods. Outburst flood compilations show a temporal increase in frequency; however, recent studies highlight the role of observational bias, creating uncertainty about current and future glacial-lake hazards. Here, we focus on the Alaska region, which generated a third of previously documented outbursts globally. Using multitemporal satellite imagery, we documented 1150 drainages from 106 ice-dammed lakes between 1985 and 2020. Documented events became more frequent over time, however, accounting for increasing image availability reveals no significant increase occurred. Most lakes decreased in area and volume, suggesting a reduction in regional flood hazard. Our satellite-based approach documented 60% more events in a 35-year period than had previously been documented over 100 years. This suggests that outburst floods have historically been underreported and warrants systematic study of other regions.

Mediating effects of inequitable gender norms on intimate partner violence and contraceptive use in a cluster randomized control trial in Niger: A causal inference mediation analysis.

Background: Gender inequity, a deeply-rooted driver of poor health globally, is expressed in society through gender norms, the unspoken rules that govern gender-related roles and behavior. The development of public health interventions focused on promoting equitable gender norms are gaining momentum internationally, but there remain critical gaps in the evidence about how these interventions are working to change behavioral outcomes. Methods: A four-arm cluster randomized control trial (cRCT) was conducted to evaluate the effects of the Reaching Married Adolescents in Niger (RMA) intervention on modern contraceptive use and intimate partner violence (IPV) among married adolescent girls and their husbands in Dosso, Niger (T1: 1042 dyads; 24 mos. follow-up: 737 dyads, 2016-2019). This study seeks to understand if changes in perceived inequitable gender norms among husbands are the mechanism behind effects on modern contraceptive use and IPV. We estimated natural direct and indirect effects via these gender norms using inverse odds ratio weighting. An intention-to-treat approach and a difference-in-differences estimator in a hierarchical linear probability model was used to estimate prevalence differences, along with bootstrapping to estimate confidence intervals. Results: The total effects of the RMA small group intervention (Arm 2) is estimated to be an 8% reduction in prevalence of IPV [95% CI: -0.18, 0.01]. For this arm, the natural indirect effect through gender inequitable social norms is associated with a 2% decrease (95% CI: -0.07, 0.12), accounting for 22.3% of this total effect, and the natural direct effect with a 6% decrease (95% CI: -0.20, -0.02) in IPV. Of the total effect of the RMA household visit intervention (Arm 1) on contraceptive use (20% increase), indirect effects via inequitable gender norms were associated with an 11% decrease (95% CI: -0.18, -0.01) and direct effects with a 32% increase (95% CI: 0.13, 0.44) in contraceptive use. For the combination arm, of the total effects on contraceptive use (19% increase), indirect effects were associated with a 9% decrease (95% CI: -0.20, 0.02) and direct effects with a 28% increase (95% CI: 0.12, 0.46). Conclusion: The present study contributes experimental evidence that the small group RMA intervention reduced IPV partially via reductions in perceived inequitable gender norms among husbands. Evidence also suggests that increases in perceived inequitable gender norms resulted in decreased contraceptive use among those receiving the household visit intervention component. Not only do these results open the "black box" around how the RMA small group intervention may create behavior change to help inform its future use, they provide evidence supporting behavior change theories and frameworks that postulate the importance of changing underlying social norms in order to reduce IPV and increase modern contraceptive use.

Retrospective investigation of sudden maternal weight loss as an indicator of impending parturition in the term gravida: a pilot study.

The aim of the study was to perform a retrospective review of records to test a possible significant association between sudden, modest weight loss (≤2 lb) between the last two prenatal appointments in the late 3rd trimester and onset of labour. Hospital and clinic records were searched for women who delivered a term baby after the onset of natural labour between 2006 and 2008, in Tulsa, OK. High-risk pregnancies were excluded. Patients were categorised by whether they lost or gained weight between their last two prenatal appointments. The groups' average times to onset of spontaneous labour were compared. A total of 149 records were obtained. Mothers who lost weight had an average onset of spontaneous labour in 2.30 days; their counterparts' average was 2.34 days. Student's t-test and Wilcoxon test p values were 0.95 and 0.61, respectively. A Kolmogorov-Smirnov test p value was 0.2139. A one-half standard deviation difference in time to delivery, approximately 2.5 days, was detectable with 0.95 probability. It was concluded that these data may be the first time this question has been investigated and provide evidence that sudden, modest weight loss at the end of pregnancy is not associated with shorter time to onset of natural labour.

Costs and economies of scale in the accelerated program for prevention of mother-to-child transmission of HIV in Zimbabwe.

BACKGROUND: Despite a growing body of literature on HIV service costs in sub-Saharan Africa, only a few studies have estimated the facility-level cost of prevention of Mother-to-Child Transmission (PMTCT) services, and even fewer provide insights into the variation of PMTCT costs across facilities. In this study, we present the first empirical costs estimation of the accelerated program for the prevention of mother-to-child transmission of HIV in Zimbabwe and investigate the determinants of heterogeneity of the facility-level average cost per service. To understand such variation, we explored the association between average costs per service and supply-and demand-side characteristics, and quality of services. One aspect of the supply-side we explore carefully is the scale of production-which we define as the annual number of women tested or the yearly number of HIV-positive women on prophylaxis. METHODS: We collected rich data on the costs and PMTCT services provided by 157 health facilities out of 699 catchment areas in five provinces in Zimbabwe for 2013. In each health facility, we measured total costs and the number of women covered with PMTCT services and estimated the average cost per woman tested and the average cost per woman on either ARV prophylaxis or ART. We refer to these facility-level average costs per service as unitary costs. We also collected information on potential determinants of the variation of unitary costs. On the supply-side, we gathered data on the scale of production, staff composition and on the types of antenatal and family planning services provided. On the demand side, we measured the total population at the catchment area and surveyed eligible pairs of mothers and infants about previous use of HIV testing and prenatal care, and on the HIV status of both mothers and infants. We explored the determinants of unitary cost variation using a two-stage linear regression strategy. RESULTS: The average annual total cost of the PMTCT program per facility was US$16,821 (median US$8,920). The average cost per pregnant woman tested was US$80 (median US$47), and the average cost per HIV-positive pregnant woman initiated on ARV prophylaxis or treatment was US$786 annually (median US$420). We found substantial heterogeneity of unitary costs across facilities regardless of facility type. The scale of production was a strong predictor of unitary costs variation across facilities, with a negative and statistically significant correlation between the two variables (p<0.01). CONCLUSIONS: These findings are the first empirical estimations of PMTCT costs in Zimbabwe. Unitary costs were found to be heterogeneous across health facilities, with evidence consistent with economies of scale.

Clinical considerations for spinal surgery in the osteoporotic patient: A comprehensive review.

Osteoporosis is a skeletal condition characterized by low bone mineral density (BMD). Common in older patients undergoing spinal fusion, it is a significant risk factor for instrumentation failure and related complications. The objective of this review is to articulate clear suggestions for screening and medical/surgical management strategies in patients with osteoporosis. A thorough review of the literature was conducted using PubMed. Varied search terms were applied to yield published manuscripts on osteoporosis and spine surgery. Biomechanical studies and studies conducted in animal models were excluded. Screening should be considered in those that present with multiple risk factors for low BMD. Dual-energy x-ray absorptiometry (DEXA) remains the gold standard, but Hounsfield Units (HU) have emerged as a powerful complement to DEXA. While both bisphosphonates and teriparatide have been investigated in the perioperative setting and have a positive impact on outcomes, teriparatide maintains an advantage in comparative studies. Surgical treatment need not be postponed. Standard surgical modifications such as using multiple points of fixation, varied fixation equipment, anterior/posterior instrumentation, and modified screw design/trajectories should all be considered. However, recent clinical studies focus on cement augmentation and expandable pedicle screws. All have been shown to improve bone-screw interface strength, but extravasation remains a risk of cement augmentation, and hydroxyapatite cement (HAC), while an emerging alternative to polymethyl methacrylate (PMMA), is not as well investigated in the setting of osteoporosis. Furthermore, research on expandable pedicle screws is limited. To conclude, optimizing spine surgery outcomes in the osteoporotic patient is possible with a thorough preoperative workup, medical management, and a tailoring of the surgical technique. This is especially important when performing complex spinal instrumentation.

Safety and pharmacokinetics of motesanib in combination with gemcitabine for the treatment of patients with solid tumours.

The aim of this open-label phase 1b study was to assess the safety and pharmacokinetics of motesanib in combination with gemcitabine in patients with advanced solid tumours. Eligible patients with histologically or cytologically documented solid tumours or lymphoma were enroled in three sequential, dose-escalating cohorts to receive motesanib 50 mg once daily (QD), 75 mg two times daily (BID), or 125 mg QD in combination with gemcitabine (1000 mg m(-2)). The primary end point was the incidence of dose-limiting toxicities (DLTs). Twenty-six patients were enroled and received motesanib and gemcitabine. No DLTs occurred. The 75 mg BID cohort was discontinued early; therefore, 125 mg QD was the maximum target dose. Sixteen patients (62%) experienced motesanib-related adverse events, most commonly lethargy (n=6), diarrhoea (n=4), fatigue (n=3), headache (n=3), and nausea (n=3). The pharmacokinetics of motesanib and of gemcitabine were not markedly affected after combination therapy. The objective response rate was 4% (1 of 26), and 27% (7 of 26) of patients achieved stable disease. In conclusion, treatment with motesanib plus gemcitabine was well tolerated, with adverse event and pharmacokinetic profiles similar to that observed in monotherapy studies.

Increased platelet arachidonic acid metabolism in diabetes mellitus.

Platelets obtained from some diabetic patients show enhanced in vitro platelet aggregation. This study sought to determine if platelet obtained from insulin-dependent diabetic subjects synthesize increased quantities of the labile aggregating substance, thromboxane A2 (TXA2), and if it may play a role in the enhanced platelet aggregation. Arachidonic acid (1 mM)-stimulated TXA2 synthesis, as determined via radioimmunoassay of its stable metabolite TXB2, was significantly greater (P less than 0.01, N = 12) in platelet-rich plasma obtained from diabetics compared with matched controls. Arachidonic acid-stimulated TXB2 synthesis in the diabetic platelet-rich plasma was positively correlated with the ambient fasting plasma glucose (r = 0.61, P less than 0.02, N = 15). Platelet aggregation induced by arachidonic acid (0.4-0.8 mM) was inhibited significantly less by 13-azaprostanoic acid (P less than 0.04, N = 14), a competitive antagonist of the actions of prostaglandin H2 or TXA2 on platelets, compared with matched controls. The results support the notion that platelets obtained from some insulin-dependent diabetic subjects manifest increased synthesis of TXA2, which may contribute to the enhanced platelet aggregation.

Dysregulation of insulin secretion in children with congenital hyperinsulinism due to sulfonylurea receptor mutations.

Mutations in the high-affinity sulfonylurea receptor (SUR)-1 cause one of the severe recessively inherited diffuse forms of congenital hyperinsulinism or, when associated with loss of heterozygosity, focal adenomatosis. We hypothesized that SUR1 mutations would render the beta-cell insensitive to sulfonylureas and to glucose. Stimulated insulin responses were compared among eight patients with diffuse hyperinsulinism (two mutations), six carrier parents, and ten normal adults. In the patients with diffuse hyperinsulinism, the acute insulin response to intravenous tolbutamide was absent and did not overlap with the responses seen in either adult group. There was positive, albeit significantly blunted, acute insulin response to intravenous dextrose in the patients with diffuse hyperinsulinism. Graded infusions of glucose, to raise and then lower plasma glucose concentrations over 4 h, caused similar rises in blood glucose but lower peak insulin levels in the hyperinsulinemic patients. Loss of acute insulin response to tolbutamide can identify children with diffuse SUR1 defects. The greater response to glucose than to tolbutamide indicates that ATP-sensitive potassium (KATP) channel-independent pathways are involved in glucose-mediated insulin release in patients with diffuse SUR1 defects. The diminished glucose responsiveness suggests that SUR1 mutations and lack of KATP channel activity may contribute to the late development of diabetes in patients with hyperinsulinism independently of subtotal pancreatectomy.

Utility of clinical swallowing examination measures for detecting aspiration post-stroke.

The purpose of this investigation was to determine the utility of clinical swallowing examination (CSE) measures for detecting aspiration as defined by videofluoroscopic swallowing examination (VFSE). This study, involving 165 participants, is a follow-up to a previously published investigation of 60 participants. Findings are compared with that investigation as well as with other research on CSEs. The results suggest that clinicians can make an accurate judgment of the occurrence of aspiration in most post-stroke patients. However, ruling out aspiration when it is absent appears more problematic. More work needs to be done if data collected from non-instrumented examinations are to be strongly predictive of the presence and absence of aspiration on VFSE. At present, there are no data to suggest that CSEs can be used to quantify aspiration or make adequate recommendations regarding patient care.

Exercise in a hot environment: comparison of two different fluid intake patterns.

AIM: Extensive research has been undertaken in the area of exercise and hydration. Most work has focused on prehydration. Less is known about different fluid intake patterns during exercise and its effect in thermoregulatory variables in hot environments. This study attempted to determine if ingesting fluid either in a single bolus or intermittently during exercise had different results in thermoregulatory parameters and thirst in a hot environment. METHODS: Six moderately trained men and women (n=6, 5 male, 1 female; mean+/-SD: age 28.5+/-2.5 y; weight 74.4+/-3.3 kg, VO2max 45.9+/-3.7 ml.kg.min-1) completed 2 exercise sessions in a randomized, counterbalanced order. Treatment 1 (bolus) consisted of 60 minutes of bicycling at 50% of VO2max in a climatic chamber (dry bulb temperature, 35 degrees C, 45% relative humidity). Subjects consumed 1 000 ml of plain cool (22 degrees C) water immediately before exercise. During treatment 2 (intermittent) the same environmental conditions were present, but subjects consumed 250 ml of water immediately before exercise. During the bicycle ride, subjects consumed 250 ml of cool water at minutes 15, 30, and 45 of exercise for a total trial volume of 1,000 ml. Tympanic ear temperatures, heart rates, rating of perceived exertion (RPE), and thirst scale data were collected immediately before exercise and at minutes 10, 20, 30, 40, 50, and 60 of exercise. RESULTS: No statistical differences were noted in temperature between treatments (P>0.05). Lower heart rates and thirst scores were noted for the bolus treatment at various time points (P<0.05). Little differences were noted between treatments for RPE during exercise. CONCLUSIONS: These results suggest that consumption of water in a single bolus is more beneficial for some aspects of thermoregulatory control and delaying thirst during exercise in the heat. Additional mechanistic studies with larger sample sizes are warranted.

Identification of a cell-surface DNA receptor and its association with systemic lupus erythematosus.

We have previously reported the existence of a cell-membrane-associated molecule on human PBMC, which binds DNA and has the characteristics of a receptor. Monoclonal antibodies have been made to this receptor and have been used successfully for the purification of this cell-surface molecule. Preliminary studies have indicated a receptor for DNA on murine kidney and spleen cells which is similar in molecular weight to the human DNA receptor (30 kD). The occurrence of autoantibodies to cell-surface receptors has been described in several autoimmune diseases and we have noted that the serum of patients with lupus and similar disorders inhibit the binding of labeled DNA to human leukocytes. Using a "dot-blot" assay with affinity-purified human DNA receptor, sera from patients with various CTD and from healthy volunteers were screened for anti-receptor antibodies; anti-receptor antibodies were found in many patients with CTD and some of their first-degree relatives. The prevalence of anti-receptor antibodies in normal blood donors was less than 2%. It is hypothesized that anti-receptor antibodies represent an early immune response in lupus and kindred disorders and that anti-DNA antibodies may arise from the corresponding anti-idiotypic response.

Acute insulin responses to leucine in children with the hyperinsulinism/hyperammonemia syndrome.

Mutations of glutamate dehydrogenase cause the hyperinsulinism/hyperammonemia syndrome by desensitizing glutamate dehydrogenase to allosteric inhibition by GTP. Normal allosteric activation of glutamate dehydrogenase by leucine is thus uninhibited, leading us to propose that children with hyperinsulinism/hyperammonemia syndrome will have exaggerated acute insulin responses to leucine in the postabsorptive state. As hyperglycemia increases beta-cell GTP, we also postulated that high glucose concentrations would extinguish abnormal responsiveness to leucine in hyperinsulinism/hyperammonemia syndrome patients. After an overnight fast, seven hyperinsulinism/hyperammonemia syndrome patients (aged 9 months to 29 yr) had acute insulin responses to leucine performed using an iv bolus of L-leucine (15 mg/kg) administered over 1 min and plasma insulin measurements obtained at -10, -5, 0, 1, 3, and 5 min. The acute insulin response to leucine was defined as the mean increase in insulin from baseline at 1 and 3 min after an iv leucine bolus. The hyperinsulinism/hyperammonemia syndrome group had excessively increased insulin responses to leucine (mean +/- SEM, 73 +/- 21 microIU/ml) compared with the control children and adults (n = 17) who had no response to leucine (1.9 +/- 2.7 microU/ml; P < 0.05). Four hyperinsulinism/hyperammonemia syndrome patients then had acute insulin responses to leucine repeated at hyperglycemia (blood glucose, 150-180 mg/dl). High blood glucose suppressed their abnormal baseline acute insulin responses to leucine of 180, 98, 47, and 28 microU/ml to 73, 0, 6, and 19 microU/ml, respectively. This suppression suggests that protein-induced hypoglycemia in hyperinsulinism/hyperammonemia syndrome patients may be prevented by carbohydrate loading before protein consumption.

Quantification of DNA binding to cell-surfaces by flow cytometry.

DNA binding to cell-surfaces has been documented in several studies. The interaction of DNA with cells has been shown to have therapeutic potential as a non-viral form of gene delivery and DNA vaccination. Recently, bacterial DNA binding and internalization has been demonstrated in some cells to trigger secretion of cytokines and cell activation. Previous studies to quantify DNA binding to cells have used radiolabeled DNA. Here we report a non-radioactive assay for quantification of cell-surface DNA binding based on the isoparametric analysis of flow cytometric data as described by Chatelier et al., Embo J., 5 (1986) 1181. This assay has the advantage over previously used procedures in not employing radioactive material and being able to discriminate viable from non-viable cells that bind DNA. With the importance of understanding the interaction of DNA with cells, this assay may have application for the identification and characterization of reagents designed to either enhance or inhibit DNA binding to cells.

Immunization of BALB/c mice with a monoclonal anti-DNA antibody induces an anti-idiotypic antibody reactive with a cell-surface DNA binding protein.

DNA binds to cell-surface proteins on human and murine leukocytes and induces secretion of the cytokine interleukin 6 (IL-6). Cell-surface DNA binding molecules have been shown to serve as target antigens for the production of autoantibodies in patients with systemic lupus erythematosus (SLE), and in lupus-prone mice. Recent studies have demonstrated that a subset of anti-anti-DNA antibodies, isolated from patients with SLE, are idiotypically related to antibodies reactive with a cell-surface DNA binding molecule. We now report that immunization of normal mice with a murine monoclonal anti-DNA antibody induces an anti-idiotypic response which has reactivity with a cell-surface DNA binding molecule. An anti-idiotypic anti-DNA monoclonal antibody (LB17) was isolated from the spleen of an immunized mouse. This monoclonal antibody blocked the binding of DNA to murine splenocytes and mimicked the functional effect of DNA by stimulating the secretion of IL-6. These experiments provide further evidence for an idiotypic connectivity between antibodies to cell-surface DNA binding proteins and anti-DNA antibodies. It is hypothesized that this idiotypic system is part of the network of natural autoantibodies and that its perturbation may give rise to pathogenic antibodies.

Psychosocial sequelae of violent victimization in a national youth sample.

In a national telephone sample of youths aged 10-16 years, over one third reported having been the victims of an assault. Victimized respondents displayed significantly more psychological and behavioral symptomatology than did nonvictimized respondents (more symptomatology related to posttraumatic stress disorder, more sadness, and more school difficulties), even after controlling for some other possible sources of distress. Sexual assault was associated with particularly high levels of symptomatology. However, victims of other forms of assault--nonfamily assaults involving weapons or physical injury (aggravated assaults), assaults by parents, violence to genitals, and attempted kidnappings--also evidenced levels of distress that were not statistically lower than those suffered by victims of sexual assault. The findings suggest that substantial mental health morbidity in the general child and adolescent population is associated with victimization.

Is youth victimization related to trauma symptoms and depression after controlling for prior symptoms and family relationships? A longitudinal, prospective study.

The common finding linking symptoms such as posttraumatic stress disorder (PTSD) and depression with youth victimization (e.g., sexual abuse) might well be artifactual if preexisting psychopathology or disturbed family relationships create a common risk for both later victimization and later symptoms. This study used a longitudinal, prospective design to examine this issue. In a national random sample telephone survey, children 10 to 16 years old were interviewed and then reinterviewed approximately 15 months later about psychological problems, family relationships and victimization experiences that had occurred in the interim. Victimization in the interim was associated with PTSD-related symptoms and depression measured at Time 2, even after controlling for these symptoms and the quality of the parent-child relationship at Time 1. The association was particularly strong for sexual abuse, parental assault, and kidnapping experiences. However, these data also suggest that some of the apparent association found in cross-sectional studies between victimization and psychopathology may be due to prior psychopathology (but not parent-child relationship problems), which puts children at risk for both victimization and later symptoms.