Preexposure Prophylaxis (PrEP) for HIV Prevention at Outpatient Substance Use Treatment Facilities, United States, 2021.

Objectives. To determine the percentage of US outpatient substance use treatment facilities that offer HIV preexposure prophylaxis (PrEP). Methods. We used a retrospective cross-sectional design with data from the National Substance Use and Mental Health Services Survey, which was administered to directors of US outpatient substance use treatment facilities in 2021. We evaluated the percentage of outpatient substance use treatment facilities offering PrEP and factors associated with the likelihood of offering PrEP. Results. We included 12 182 outpatient substance use treatment facilities. Of these, 637 (5.2%) offered PrEP. Offering HIV treatment (adjusted odds ratio [AOR] = 45.3; 95% confidence interval [CI] = 36.0, 56.9) and offering programs for LGBTQ (lesbian, gay, bisexual, transgender, and queer or questioning) people (AOR = 1.3; 95% CI = 1.0, 1.6) were associated with higher likelihoods of offering PrEP. Conclusions. PrEP is highly effective and recommended for patients at risk for HIV from injection drug use. Nearly 95% of US outpatient substance use treatment facilities did not offer PrEP-a missed opportunity for harm reduction through primary HIV prevention. Public Health Implications. Diversification of the array of available HIV PrEP options and the ongoing HIV and opioid use epidemics require outpatient substance use treatment facilities to expand PrEP availability. (Am J Public Health. 2024;114(8):833-837. https://doi.org/10.2105/AJPH.2024.307699).

Sex-specific threat responding and neuronal engagement in carbon dioxide associated fear and extinction: Noradrenergic involvement in female mice.

Difficulty in appropriately responding to threats is a key feature of psychiatric disorders, especially fear-related conditions such as panic disorder (PD) and posttraumatic stress disorder (PTSD). Most prior work on threat and fear regulation involves exposure to external threatful cues. However, fear can also be triggered by aversive, within-the-body, sensations. This interoceptive signaling of fear is highly relevant to PD and PTSD but is not well understood, especially in the context of sex. Using female and male mice, the current study investigated fear-associated spontaneous and conditioned behaviors to carbon dioxide (CO2) inhalation, a potent interoceptive threat that induces fear and panic. We also investigated whether behavioral sensitivity to CO2 is associated with delayed PTSD-relevant behaviors. CO2 evoked heterogenous freezing behaviors in both male and female animals. However, active, rearing behavior was significantly reduced in CO2-exposed male but not female mice. Interestingly, behavioral sensitivity to CO2 was associated with compromised fear extinction, independent of sex. However, in comparison to CO2-exposed males, females elicited less freezing and higher rearing during extinction suggesting an engagement of active versus passive defensive coping. Persistent neuronal activation marker ΔFosB immuno-mapping revealed attenuated engagement of infralimbic-prefrontal areas in both sexes but higher activation of brain stem locus coeruleus (LC) area in females. Inter-regional co-activation mapping revealed sex-independent disruptions in the infralimbic-amygdala associations but altered LC associations only in CO2-exposed female mice. Lastly, dopamine ß hydroxylase positive (DßH + ve) noradrenergic neuronal cell counts in the LC correlated with freezing and rearing behaviors during CO2 inhalation and extinction only in female but not male mice. Collectively, these data provide evidence for higher active defensive responding to interoceptive threat CO2-associated fear in females that may stem from increased recruitment of the brainstem noradrenergic system. Our findings reveal distinct contributory mechanisms that may promote sex differences in fear and panic associated pathologies.

Aberrant Neurofunctional Responses During Emotional and Attentional Processing Differentiate ADHD Youth With and Without a Family History of Bipolar I Disorder.

OBJECTIVE: To compare neurofunctional responses in emotional and attentional networks of psychostimulant-free ADHD youth with and without familial risk for bipolar I disorder (BD). METHODS: ADHD youth with (high-risk, HR, n = 48) and without (low-risk, LR, n = 50) a first-degree relative with BD and healthy controls (n = 46) underwent functional magnetic resonance imaging while performing a continuous performance task with emotional distracters. Region-of-interest analyses were performed for bilateral amygdala (AMY), ventrolateral (VLPFC) and dorsolateral (DLPFC) prefrontal cortex, and anterior (ACC) and posterior cingulate cortex (PCC). RESULTS: Compared with HC, HR, but not LR, exhibited predominantly left-lateralized AMY, VLPFC, DLPFC, PCC, and rostral ACC hyperactivation to emotional distractors, whereas LR exhibited right VLPFC and bilateral dorsal ACC hypoactivation to attentional targets. Regional responses correlated with emotional and attention symptoms. CONCLUSION: Aberrant neurofunctional responses during emotional and attentional processing differentiate ADHD youth with and without a family history of BD and correlate with relevant symptoms ratings.

The relationship between reincarceration and treatment of opioid use disorder with extended-release naltrexone among persons with HIV.

Background: In the United States, a disproportionate number of persons with HIV (PWH) and opioid use disorder (OUD) are involved in the justice system. Medications for OUD (MOUD) can reduce convictions and incarceration time in persons with OUD. Extended-release naltrexone (XR-NTX) has been shown to reduce craving of opioids, recurrence of use, and overdose and help achieve or maintain HIV viral suppression in PWH with OUD involved with the justice system. Objectives: This retrospective study aimed to describe factors associated with reincarceration and to evaluate if XR-NTX was associated with reduced reincarceration among PWH and OUD who were released to the community from incarceration. Methods: Data from participants released to the community from incarceration from a completed randomized controlled trial was analyzed using a generalized linear model to estimate odds ratios associated with reincarceration and a Kaplan-Meier survival analysis to determine time to reincarceration and non-reincarcerated individuals were compared. Results: Of the 77 participants, 41 (53.2%) were reincarcerated during the 12-month study period. The mean time to reincarceration was 190 days (SD=108.3). Compared with participants who remained in the community, reincarcerated participants were more likely to have major depressive disorder at study baseline, increased opioid cravings, longer mean lifetime incarceration, and a higher physical quality of life score. XR-NTX was not significantly associated statistically with reincarceration in this analysis. Conclusion: Reducing reincarceration is a public health priority, given the high proportion of PWH and OUD in the U.S. justice system as well as high degrees of persons returning to the community and having care interrupted due to reincarceration. This analysis determined that potentially identifying depression in recently released individuals could improve HIV outcomes, decrease recurrence of opioid use, and reduce reincarceration.

The MedSafer Study-Electronic Decision Support for Deprescribing in Hospitalized Older Adults: A Cluster Randomized Clinical Trial.

IMPORTANCE: Scalable deprescribing interventions may reduce polypharmacy and the use of potentially inappropriate medications (PIMs); however, few studies have been large enough to evaluate the impact that deprescribing may have on adverse drug events (ADEs). OBJECTIVE: To evaluate the effect of an electronic deprescribing decision support tool on ADEs after hospital discharge among older adults with polypharmacy. DESIGN, SETTING, AND PARTICIPANTS: This was a cluster randomized clinical trial of older (≥65 years) hospitalized patients with an expected survival of more than 3 months who were admitted to 1 of 11 acute care hospitals in Canada from August 22, 2017, to January 13, 2020. At admission, participants were taking 5 or more medications per day. Data analyses were performed from January 3, 2021, to September 23, 2021. INTERVENTIONS: Personalized reports of deprescribing opportunities generated by MedSafer software to address usual home medications and measures of prognosis and frailty. Deprescribing reports provided to the treating team were compared with usual care (medication reconciliation). MAIN OUTCOMES AND MEASURES: The primary outcome was a reduction of ADEs within the first 30 days postdischarge (including adverse drug withdrawal events) captured through structured telephone surveys and adjudicated blinded to intervention status. Secondary outcomes were the proportion of patients with 1 or more PIMs deprescribed at discharge and the proportion of patients with an adverse drug withdrawal event (ADWE). RESULTS: A total of 5698 participants (median [range] age, 78 [72-85] years; 2858 [50.2%] women; race and ethnicity data were not collected) were enrolled in 3 clusters and were adjudicated for the primary outcome (control, 3204; intervention, 2494). Despite cluster randomization, there were group imbalances, eg, the participants in the intervention arm were older and had more PIMS prescribed at baseline. After hospital discharge, 4989 (87.6%) participants completed an ADE interview. There was no significant difference in ADEs within 30 days of discharge (138 [5.0%] of 2742 control vs 111 [4.9%] of 2247 intervention participants; adjusted risk difference [aRD] -0.8%; 95% CI, -2.9% to 1.3%). Deprescribing increased from 795 (29.8%) of 2667 control to 1249 (55.4%) of 2256 intervention participants [aRD, 22.2%; 95% CI, 16.9% to 27.4%]. There was no difference in ADWEs between groups. Several post hoc sensitivity analyses, including the use of a nonparametric test to address the low cluster number, group imbalances, and potential biases, did not alter study conclusions. CONCLUSIONS AND RELEVANCE: This cluster randomized clinical trial showed that providing deprescribing clinical decision support during acute hospitalization had no demonstrable impact on ADEs, although the intervention was safe and led to improvements in deprescribing. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03272607.

Subfornical organ interleukin 1 receptor: A novel regulator of spontaneous and conditioned fear associated behaviors in mice.

Impaired threat responding and fear regulation is a hallmark of psychiatric conditions such as post-traumatic stress disorder (PTSD) and Panic Disorder (PD). Most studies have focused on external psychogenic threats to study fear, however, accumulating evidence suggests a primary role of homeostatic perturbations and interoception in regulating emotional behaviors. Heightened reactivity to interoceptive threat carbon dioxide (CO2) inhalation associates with increased risk for developing PD and PTSD, however, contributory mechanisms and molecular targets are not well understood. Previous studies from our group suggested a potential role of interleukin 1 receptor (IL-1R1) signaling within BBB-devoid sensory circumventricular organ, the subfornical organ (SFO) in CO2-evoked fear. However, the necessity of SFO-IL-1R1 in regulating CO2-associated spontaneous fear as well as, long-term fear potentiation relevant to PD/PTSD has not been investigated. The current study tested male mice with SFO-targeted microinfusion of the IL-1R1 antagonist (IL-1RA) or vehicle in a recently developed CO2-startle-fear conditioning-extinction paradigm. Consistent with our hypothesis, SFO IL-1RA treatment elicited significant attenuation of freezing and increased rearing during CO2 inhalation suggesting SFO-IL1R1 regulation of spontaneous fear to CO2. Intriguingly, SFO IL-1RA treatment normalized CO2-associated potentiation of conditioned fear and impaired extinction a week later suggesting modulation of long-term fear by SFO-IL-1R1 signaling. Post behavior FosB mapping revealed recruitment of prefrontal cortex-amygdala-periaqueductal gray (PAG) areas in SFO-IL-1RA mediated effects. Additionally, we localized cellular IL-1R1 expression within the SFO to blood vessel endothelial cells and observed CO2-induced alterations in IL-1ß/IL-1R1 expression in peripheral mononuclear cells and SFO. Lastly, CO2-evoked microglial activation was attenuated in SFO-IL-1RA treated mice. These observations suggest a peripheral monocyte-endothelial-microglia interplay in SFO-IL-1R1 modulation of CO2-associated spontaneous fear and delayed fear memory. Collectively, our data highlight a novel, "bottom-up" neuroimmune mechanism that integrates interoceptive and exteroceptive threat processing of relevance to fear-related pathologies.

An Examination of Perceived Pressure From Stakeholders on Concussion Reporting Intentions and Behavior in Ice Hockey Athletes.

OBJECTIVE: We aimed to assess whether perceived pressure predicts concussion reporting intentions and behavior in youth, high school, and collegiate ice hockey athletes, and, secondarily, whether perceived pressure from stakeholders differed between sex or level of play. SETTING: Online survey. PARTICIPANTS: One hundred fifty-two ice hockey athletes (males: n = 96, 63.2%; females: n = 55, 36.2%; missing: n = 1, 0.7%; age = 14.04 ± 3.6 years). DESIGN: Cross-sectional. MAIN MEASURES: Respondents answered a survey that elicited information about demography, perceived pressure from 6 stakeholders, and concussion reporting intentions and behavior. For the first aim, we used a generalized linear model to determine whether perceived pressure from any stakeholder predicted intention (symptom reporting, concussion reporting, and intention beliefs) or behavior ("all concussions," "not obvious concussions"; α < .05) while controlling for level of play. To determine whether pressure from any stakeholder predicted symptom reporting behavior, we used logistic regression while controlling for level of play. For the second aim, to examine sex differences in perceived pressure from each stakeholder, we employed Mann-Whitney tests and to examine level of play differences, we used Kruskal-Wallis tests. RESULTS: Controlling for level of play, a 1-point increase in perceived pressure from parents and athletic administrators decreased concussion reporting intentions by 0.92 (P = .004) and 1.09 (P = .005) points, respectively. Perceived pressure from a sports medicine professional decreased intention beliefs by 0.17 (P = .029) points. Perceived pressure from stakeholders did not predict symptom reporting (P = .440) or "not obvious concussion" reporting (P = .655) behavior. We observed no difference in perceived pressure across stakeholders (all P values >.05); however, collegiate ice hockey respondents perceived greater pressure from coaches than youth or high school athletes (P < .001). We noted no other differences in perceived pressure across levels of play (all P values >.05). CONCLUSIONS: Concussion reporting intentions were negatively influenced by perceived pressure from parents, athletic administrators, and sports medicine professionals, but these findings did not translate to reporting behavior.

Determining the Prognosis of Bell's Palsy Based on Severity at Presentation and Electroneuronography.

OBJECTIVE: To examine the demographics of Bell's palsy and determine how House-Brackmann (HB) grade at nadir and electroneuronography (ENoG) results correlate with HB grade after recovery and development of synkinesis. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care military medical center. METHODS: Patients with acute Bell's palsy and adequate follow-up, defined as 6 months or return to HB grade I function, were included. Demographic information, HB scores at nadir and recovery, and ENoG results were collected. RESULTS: A total of 112 patient records were analyzed. Ages ranged from 8 to 87 years with peaks at 21 to 25 and 61 to 65 years. Among patients, 16.3% reached a nadir at HB II, 41.9% at HB III, 5.4% at HB IV, 16.3% at HB V, and 20.1% at HB VI. The overall recovery rate was 73.2% to HB I function, 17.0% to HB II, and 9.8% to HB III. The chance of recovery to HB I decreased as the severity of paralysis increased (rs = -1.0, P < .0001). Mean time to recovery to HB I was 6 weeks. Greater degeneration on ENoG suggested worse recovery (rs = 0.62, P = .01). Patients with HB V and VI were most likely to develop synkinesis. CONCLUSION: More severe paralysis increased the chance of recovery to HB II or III function. The granularity of this study provides prognostic insights that may inform the counseling of patients with Bell's palsy with respect to prognosis and recovery timeline.

The Angel Wings Incision: A novel solution for mastectomy patients with increased lateral adiposity.

Many techniques have been proposed to address the problem of increased lateral adiposity in patients undergoing mastectomy, however, there is no standard approach. This cosmetic deformity at the lateral end of the mastectomy scar, also known as a dog ear, is especially common in obese patients. This defect can be unsightly and uncomfortable. We describe a technique for creating a winged incision to eliminate the dog ear deformity. The Angel Wings Incision results in tissue flaps that create a smooth body contour upon closure in patients with increased lateral adiposity. The technique is reproducible, aesthetically pleasing, and improves patient satisfaction.

Direct oral anticoagulants versus aspirin for venous thromboembolism prophylaxis after orthopedic surgery.

PURPOSE: The risks of venous thromboembolism (VTE) and bleeding with direct oral anticoagulants (DOACs) and aspirin for thromboprophylaxis after orthopedic surgery were studied. METHODS: A single center, retrospective study was conducted to examine patients who underwent a major orthopedic surgery from 2011 to 2015. The primary endpoint evaluated was the net clinical outcome of bleeding and thrombosis rates between the DOAC and aspirin groups. Secondary endpoints included bleeding rates, thrombosis rates, transfusion rates, and 90-day readmission rates. The primary endpoint was analyzed using adjusted logistic regression model with propensity score added as an independent variable. RESULTS: A total of 420 patients were included in this study. The proportion of patients with composite primary outcome was similar between the groups (12.9% and 13.3%, in the DOAC and aspirin groups, respectively; p > 0.5). VTE events were numerically lower in the DOAC group, but the result was not statistically significant. Readmission due to VTE or bleeding and bleeding events were also similar between the groups. The DOAC group had a higher proportion of blood transfusions of at least 2 units of blood postoperatively compared with the aspirin group (p = 0.04). CONCLUSION: No difference in net clinical outcome was observed in patients who received a DOAC or aspirin for VTE prophylaxis after major orthopedic surgery.

Current Pediatric Emergency Department Innovative Programs to Improve the Care of Psychiatric Patients.

Emergency departments (EDs) across North America have become a safety net for patients seeking mental health (MH) services. The prevalence of families seeking treatment of children in MH crisis has become a national emergency. To address MH access and improve quality and efficient management of children with MH conditions, the authors describe ED projects targeting this vulnerable population. Five North American health care systems volunteered to feature projects that seek to reduce ED visits and/or improve the care of MH patients: Allina Health, Nationwide Children's Hospital, Children's Hospital of Eastern Ontario, Connecticut Children's Medical Center, and Rhode Island Hospital.

Transaortic gunshot wound through perivisceral segment successfully managed by placement of thoracic stent graft.

We describe a 36-year-old woman who presented to our facility after sustaining a gunshot wound to the epigastric region. The gunshot resulted in injury to the left lobe of the liver and the twelfth thoracic vertebral body as well as in a through-and-through injury to the abdominal aorta at the level of the celiac axis. The vascular injury was managed successfully by placement of a thoracic stent graft with coverage of the celiac axis. This case demonstrates the feasibility of managing this uncommon injury with endovascular techniques.

Clinical signs, treatment, and prognostic factors for dogs with histoplasmosis.

OBJECTIVE To determine the clinical manifestations of histoplasmosis in a large sample of dogs, compare outcomes achieved with fluconazole versus itraconazole, and identify variables available at the time of diagnosis with prognostic value. DESIGN Retrospective case series with nested cohort study. ANIMALS 79 dogs with confirmed histoplasmosis evaluated at 2 veterinary teaching hospitals from 1999 through 2015. PROCEDURES Medical records were reviewed and data extracted regarding clinical signs at evaluation, physical examination findings, clinical laboratory values, other diagnostic test results, treatments, and outcomes. Data were compared between antifungal agents used (fluconazole or itraconazole) and between other variables. RESULTS Various breeds were represented. Working and herding breeds had mostly disseminated histoplasmosis, and toy breeds had mostly the gastrointestinal form. The diagnosis was often achieved with noninvasive techniques, such as cytologic evaluation of rectal scrape samples (n = 24) or blood films (15). Clinical remission was achieved in 16 of 25 (64%) dogs receiving fluconazole and 17 of 24 (71%) dogs receiving itraconazole. No differences were identified between antifungal agents in survival, clinical remission, or disease relapse rates. Identified negative prognostic factors included Great Pyrenees breed, dyspnea, need for oxygen supplementation, icterus, palpable abdominal organomegaly, anemia, thrombocytopenia, hypercalcemia, high serum alkaline phosphatase activity, and hyperbilirubinemia, whereas diarrhea was a positive prognostic factor. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that histoplasmosis should be considered in a sick dog of any breed in an endemic area. Clinical signs may be nonspecific. Diagnosis may often be possible with noninvasive and inexpensive tests. Either fluconazole or itraconazole may be an effective treatment option.

Comparison of Antifactor Xa and Activated Partial Thromboplastin Time Monitoring for Heparin Dosing in Vascular Surgery Patients: A Single-Center Retrospective Study.

BACKGROUND: Vascular surgery patients often require anticoagulation with intravenous unfractionated heparin monitored through antifactor Xa (anti-Xa) levels or the activated partial thromboplastin time (aPTT). This study compares the 2 monitoring strategies in terms of major bleeding events in the vascular surgery population. METHODS: This was a single-center, retrospective study that included patients treated with a pharmacy-managed heparin protocol monitored by either anti-Xa or aPTT after vascular surgery. The primary outcome was the percentage of patients experiencing major bleeding events after procedure. Secondary outcomes evaluated minor bleeding episodes, postprocedure packed red blood cell transfusions, and the incidence of thrombotic events. In a secondary analysis, simultaneously measured anti-Xa and aPTT values were identified and analyzed for discordance. RESULTS: Major bleeding occurred in 12/72 patients (17%) on the anti-Xa-monitored protocol versus 5/62 patients (8%) on the aPTT-monitored protocol (P = 0.19). Minor bleeding episodes were documented in 10% of the patients in the anti-Xa group versus 6% in the aPTT group (P = 0.54). There were no significant differences between the 2 groups in packed red blood cell transfusions and thrombotic events. Of 109 pairs of simultaneously measured anti-Xa and aPTT values, 39 pairs (36%) showed relatively high aPTT values compared with corresponding anti-Xa levels. Nine patients who had these discordant test results experienced bleeding while their heparin drip was titrated based on lower anti-Xa values. CONCLUSIONS: The use of anti-Xa levels for heparin titration showed higher rates of major bleeding complications in vascular surgery patients compared with aPTT monitoring, but no significant difference was identified in this study. Vascular surgery patients with relatively high aPTT to anti-Xa values may have an increased risk of bleeding complications when heparin is titrated based on anti-Xa levels.

Disseminated phaeohyphomycosis in a dog.

Phaeohyphomycosis is a rare but emerging disease caused by dematiaceous fungi. Here we describe the case of an immunosuppressed dog with disseminated phaeohyphomycosis secondary to Bipolaris spicifera infection. Regionally extensive infiltration of the paw pads, skin, myocardium, liver, renal interstitium and diaphragm was identified on histopathology. Candida glabrata and Fusarium oxysporum were also cultured from multiple sites post-mortem. The dog was treated with fluconazole, itraconazole, terbinafine and liposomal amphotericin B, but was euthanized due to its poor prognosis after 12 days of therapy.

Association between health literacy and 30-day healthcare use after hospital discharge in the heart failure population.

BACKGROUND: Low health literacy increases the risk for hospital readmissions. Despite this, the measurement and use of health literacy to guide discharge counseling and planning in heart failure patients is not commonly performed. A short 3-Question Brief Health Literacy Screen (BHLS) is available and takes less than three minutes to complete, but has never been evaluated to help determine whether health literacy affects healthcare use after discharge in patients with heart failure. OBJECTIVE: The purpose of this study was to assess 30-day readmissions and emergency department visits based on health literacy evaluated by the BHLS in an acute care heart failure population. METHODS: This was a prospective observational cohort study conducted at a large quaternary health system. Hospitalized patients with a diagnosis of heart failure were assessed for health literacy using the BHLS. Unplanned healthcare use after discharge including 30-day, all-cause ED visits and hospital readmissions was assessed using univariate and logistic regression models. RESULTS: Two hundred and sixty four patients aged 66.6 ± 14.3 (mean ± SD) years met inclusion/exclusion criteria of whom 175 (66.3%) had a BHLS score >9 (adequate health literacy) and 89 (33.7%) had a BHLS score ≤9 (low health literacy). Predictors of low health literacy included older age (p = 0.019), lower education level (p < 0.001) and unemployed (p = 0.048). After controlling for potential confounders, low health literacy was independently associated with 30-day healthcare use after hospital discharge (OR:1.80; 95% CI: 1.04-3.11; p = 0.035). CONCLUSION: Using a short, 3-question validated survey instrument, it was demonstrated that low health literacy was associated with increased 30-day unplanned healthcare use after discharge in this heart failure population. These results provide a clinically useful, easily incorporated tool that could identify high-risk patients at need for clinical interventions.

Transcomplementation and synergism in plants: implications for viral transgenes?

In plants, viral synergisms occur when one virus enhances infection by a distinct or unrelated virus. Such synergisms may be unidirectional or mutualistic but, in either case, synergism implies that protein(s) from one virus can enhance infection by another. A mechanistically related phenomenon is transcomplementation, in which a viral protein, usually expressed from a transgene, enhances or supports the infection of a virus from a distinct species. To gain an insight into the characteristics and limitations of these helper functions of individual viral genes, and to assess their effects on the plant-pathogen relationship, reports of successful synergism and transcomplementation were compiled from the peer-reviewed literature and combined with data from successful viral gene exchange experiments. Results from these experiments were tabulated to highlight the phylogenetic relationship between the helper and dependent viruses and, where possible, to identify the protein responsible for the altered infection process. The analysis of more than 150 publications, each containing one or more reports of successful exchanges, transcomplementation or synergism, revealed the following: (i) diverse viral traits can be enhanced by synergism and transcomplementation; these include the expansion of host range, acquisition of mechanical transmission, enhanced specific infectivity, enhanced cell-to-cell and long-distance movement, elevated or novel vector transmission, elevated viral titre and enhanced seed transmission; (ii) transcomplementation and synergism are mediated by many viral proteins, including inhibitors of gene silencing, replicases, coat proteins and movement proteins; (iii) although more frequent between closely related viruses, transcomplementation and synergism can occur between viruses that are phylogenetically highly divergent. As indicators of the interoperability of viral genes, these results are of general interest, but they can also be applied to the risk assessment of transgenic crops expressing viral proteins. In particular, they can contribute to the identification of potential hazards, and can be used to identify data gaps and limitations in predicting the likelihood of transgene-mediated transcomplementation.

The mutational consequences of plant transformation.

Plant transformation is a genetic engineering tool for introducing transgenes into plant genomes. It is now being used for the breeding of commercial crops. A central feature of transformation is insertion of the transgene into plant chromosomal DNA. Transgene insertion is infrequently, if ever, a precise event. Mutations found at transgene insertion sites include deletions and rearrangements of host chromosomal DNA and introduction of superfluous DNA. Insertion sites introduced using Agrobacterium tumefaciens tend to have simpler structures but can be associated with extensive chromosomal rearrangements, while those of particle bombardment appear invariably to be associated with deletion and extensive scrambling of inserted and chromosomal DNA. Ancillary procedures associated with plant transformation, including tissue culture and infection with A tumefaciens, can also introduce mutations. These genome-wide mutations can number from hundreds to many thousands per diploid genome. Despite the fact that confidence in the safety and dependability of crop species rests significantly on their genetic integrity, the frequency of transformation-induced mutations and their importance as potential biosafety hazards are poorly understood.