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Juvenile idiopathic epilepsy (JIE) is a self-limiting neurological disorder with a suspected genetic predisposition affecting young Arabian foals of the Egyptian lineage. The condition is characterized by tonic-clonic seizures with intermittent post-ictal blindness, in which most incidents are sporadic and unrecognized. This study aimed to identify genetic components shared across a local cohort of Arabian foals diagnosed with JIE via a combined whole genome and targeted resequencing approach: Initial whole genome comparisons between a small cohort of nine diagnosed foals (cases) and 27 controls from other horse breeds identified variants uniquely shared amongst the case cohort. Further validation via targeted resequencing of these variants, that pertain to non-intergenic regions, on additional eleven case individuals revealed a single 19bp deletion coupled with a triple-C insertion (Δ19InsCCC) within the TRIM39-RPP21 gene readthrough that was uniquely shared across all case individuals, and absent from three additional Arabian controls. Furthermore, we have confirmed recent findings refuting potential linkage between JIE and other inherited diseases in the Arabian lineage, and refuted the potential linkage between JIE and genes predisposing a similar disorder in human newborns. This is the first study to report a genetic variant to be shared in a sub-population cohort of Arabian foals diagnosed with JIE. Further evaluation of the sensitivity and specificity of the Δ19InsCCC allele within additional cohorts of the Arabian horse is warranted in order to validate its credibility as a marker for JIE, and to ascertain whether it has been introduced into other horse breeds by Arabian ancestry.

Background: Evidence is accumulating that coronavirus disease 2019 increases the risk of hospitalization and mechanical ventilation in pregnant patients and for preterm delivery. However, the impact on maternal mortality and whether morbidity is differentially affected by disease severity at delivery and trimester of infection are unknown., Objective: This study aimed to describe disease severity and outcomes of severe acute respiratory syndrome coronavirus 2 infections in pregnancy across the Washington State, including pregnancy complications and outcomes, hospitalization, and case fatality., Study Design: Pregnant patients with a polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection between March 1, 2020, and June 30, 2020, were identified in a multicenter retrospective cohort study from 35 sites in Washington State. Sites captured 61% of annual state deliveries. Case-fatality rates in pregnancy were compared with coronavirus disease 2019 fatality rates in similarly aged adults in Washington State using rate ratios and rate differences. Maternal and neonatal outcomes were compared by trimester of infection and disease severity at the time of delivery., Results: The principal study findings were as follows: (1) among 240 pregnant patients in Washington State with severe acute respiratory syndrome coronavirus 2 infections, 1 in 11 developed severe or critical disease, 1 in 10 were hospitalized for coronavirus disease 2019, and 1 in 80 died; (2) the coronavirus disease 2019-associated hospitalization rate was 3.5-fold higher than in similarly aged adults in Washington State (10.0% vs 2.8%; rate ratio, 3.5; 95% confidence interval, 2.3-5.3); (3) pregnant patients hospitalized for a respiratory concern were more likely to have a comorbidity or underlying conditions including asthma, hypertension, type 2 diabetes mellitus, autoimmune disease, and class III obesity; (4) 3 maternal deaths (1.3%) were attributed to coronavirus disease 2019 for a maternal mortality rate of 1250 of 100,000 pregnancies (95% confidence interval, 257-3653); (5) the coronavirus disease 2019 case fatality in pregnancy was a significant 13.6-fold (95% confidence interval, 2.7-43.6) higher in pregnant patients than in similarly aged individuals in Washington State with an absolute difference in mortality rate of 1.2% (95% confidence interval, -0.3 to 2.6); and (6) preterm birth was significantly higher among women with severe or critical coronavirus disease 2019 at delivery than for women who had recovered from coronavirus disease 2019 (45.4% severe or critical coronavirus disease 2019 vs 5.2% mild coronavirus disease 2019; P<.001)., Conclusion: Coronavirus disease 2019 hospitalization and case-fatality rates in pregnant patients were significantly higher than in similarly aged adults in Washington State. These data indicate that pregnant patients are at risk of severe or critical disease and mortality compared to nonpregnant adults, and also at risk for preterm birth., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: During the early months of the coronavirus disease 2019 pandemic, risks associated with severe acute respiratory syndrome coronavirus 2 in pregnancy were uncertain. Pregnant patients can serve as a model for the success of clinical and public health responses during public health emergencies as they are typically in frequent contact with the medical system. Population-based estimates of severe acute respiratory syndrome coronavirus 2 infections in pregnancy are unknown because of incomplete ascertainment of pregnancy status or inclusion of only single centers or hospitalized cases. Whether pregnant women were protected by the public health response or through their interactions with obstetrical providers in the early months of pandemic is not clearly understood., Objective: This study aimed to estimate the severe acute respiratory syndrome coronavirus 2 infection rate in pregnancy and to examine the disparities by race and ethnicity and English language proficiency in Washington State., Study Design: Pregnant patients with a polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection diagnosed between March 1, 2020, and June 30, 2020 were identified within 35 hospitals and clinics, capturing 61% of annual deliveries in Washington State. Infection rates in pregnancy were estimated overall and by Washington State Accountable Community of Health region and cross-sectionally compared with severe acute respiratory syndrome coronavirus 2 infection rates in similarly aged adults in Washington State. Race and ethnicity and language used for medical care of pregnant patients were compared with recent data from Washington State., Results: A total of 240 pregnant patients with severe acute respiratory syndrome coronavirus 2 infections were identified during the study period with 70.7% from minority racial and ethnic groups. The principal findings in our study were as follows: (1) the severe acute respiratory syndrome coronavirus 2 infection rate was 13.9 per 1000 deliveries in pregnant patients (95% confidence interval, 8.3-23.2) compared with 7.3 per 1000 (95% confidence interval, 7.2-7.4) in adults aged 20 to 39 years in Washington State (rate ratio, 1.7; 95% confidence interval, 1.3-2.3); (2) the severe acute respiratory syndrome coronavirus 2 infection rate reduced to 11.3 per 1000 deliveries (95% confidence interval, 6.3-20.3) when excluding 45 cases of severe acute respiratory syndrome coronavirus disease 2 detected through asymptomatic screening (rate ratio, 1.3; 95% confidence interval, 0.96-1.9); (3) the proportion of pregnant patients in non-White racial and ethnic groups with severe acute respiratory syndrome coronavirus disease 2 infection was 2- to 4-fold higher than the race and ethnicity distribution of women in Washington State who delivered live births in 2018; and (4) the proportion of pregnant patients with severe acute respiratory syndrome coronavirus 2 infection receiving medical care in a non-English language was higher than estimates of pregnant patients receiving care with limited English proficiency in Washington State (30.4% vs 7.6%)., Conclusion: The severe acute respiratory syndrome coronavirus 2 infection rate in pregnant people was 70% higher than similarly aged adults in Washington State, which could not be completely explained by universal screening at delivery. Pregnant patients from nearly all racial and ethnic minority groups and patients receiving medical care in a non-English language were overrepresented. Pregnant women were not protected from severe acute respiratory syndrome coronavirus 2 infection in the early months of the pandemic. Moreover, the greatest burden of infections occurred in nearly all racial and ethnic minority groups. These data coupled with a broader recognition that pregnancy is a risk factor for severe illness and maternal mortality strongly suggested that pregnant people should be broadly prioritized for coronavirus disease 2019 vaccine allocation in the United States similar to some states., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Trauma patients are often noted to have poor compliance but high recidivism and readmission rates. Participation in a trauma recovery services (TRS) program, which provides peer support and other psychosocial resources, may impact the trajectory of patient recovery by decreasing barriers to follow-up. We hypothesized that TRS participants would have greater downstream nonemergent use of our hospital system over the year following trauma, manifested by more positive encounters, fewer negative encounters, and lower emergency department (ED) charges., Methods: We studied trauma survivors (March 2017 to March 2018) offered TRS. Hospital encounters and charges 1 year from index admission were compared between patients who accepted and declined TRS. Positive encounters were defined as outpatient visits and planned admissions; negative encounters were defined as no shows, ED visits, and unplanned admissions. Charges were grouped as cumulative ED and non-ED charges (including outpatient and subsequent admission charges). Adjusted logistic and linear regression analyses were used to identify factors associated with positive/negative encounters and ED charges., Results: Of 511 identified patients (68% male; injury severity score, 14 [9-19]), 362 (71%) accepted TRS. Trauma recovery services patients were older, had higher injury severity, and longer index admission length of stay (all p < 0.05). After adjusting for confounders, TRS patients were more likely to have at least one positive encounter and were similarly likely to have negative encounters as patients who declined services. Total aggregate charges for this group was US $74 million, of which US $30 million occurred downstream of the index admission. Accepting TRS was associated with lower ED charges., Conclusion: A comprehensive TRS program including education, peer mentors, and a support network may provide value to the patient and the health care system by reducing subsequent care provided by the ED in the year after a trauma without affecting nonemergent care., Level of Evidence: Therapeutic/care management, level IV.

Introduction: Historically, trauma patients have low adherence to recommended outpatient follow-up plans, which is crucial for improved long-term clinical outcomes. We sought to identify characteristics associated with nonadherence to recommended outpatient follow-up visits., Methods: This is a single-center retrospective examination of inpatient trauma survivors admitted to a level 1 trauma center (March 2017-March 2018). Patients with known alternative follow-up were excluded. All outpatient visits within 1 y from the index admission were identified. The primary outcome was nonadherence, which was noted if a patient failed to follow-up for any specialty recommended in the discharge instructions. Factors for nonadherence studied included age, injury severity score, mechanism, length of stay, number of referrals made, and involvement with a Trauma Recovery Services program. Bivariate and logistic regression analyses were performed., Results: A total of498 patients were identified (69% men, median age 43 y [range, 26-58 y], median injury severity score 14 [range, 9-19]). Among them, 240 (47%) were nonadherent. The most common specialties recommended were orthopedic surgery (56% referred, 19% nonadherent), trauma (54% referred, 35% nonadherent), and neurosurgery (127 referred, 35% nonadherent). Lowest levels of follow-up were seen for nonsurgical referrals. In adjusted analysis, a higher number of referrals made (odds ratio [OR], 2.45; 95% confidence interval [CI], 1.95-3.05) and older age (OR, 1.01; 95% CI, 1.00-1.02) were associated with nonadherence. Trauma Recovery Service participants and penetrating trauma patients were more likely to be adherent (OR, 0.60; 95% CI, 0.37-0.97)., Conclusions: The largest contributor to nonadherence was the number of referrals made; patients who were referred to multiple specialists were more likely to be nonadherent. Peer support services may lower barriers to follow-up., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Resilience is crucial for students in health schools as care becomes more complex and as the adjustment to meet patient, environmental, and professional demands with success can seem a daunting challenge. Self-care activities can support the development of resilience in the student population. The purpose of this study is to explore and describe self-care practices, health-promoting behaviors, and resilience among students, faculty, and staff of the health professional schools at a large metropolitan university. Method: This was a cross-sectional study of data from 148 participants. Analysis included descriptive statistics, t tests, analysis of variance, crosstabs, and Pearson correlations. Results: Resilience was lower among students than among faculty and staff. The most frequent self-care activities were humor and music. Resilience was significantly correlated with the self-care behaviors of praying ( p = .006), healthy sleeping habits ( p = .024), reading ( p = .007), and mindful acceptance ( p = .025); yoga and meditation were not significantly correlated with resilience.

Genetic variants that are associated with susceptibility to type 2 diabetes (T2D) are important for identification of individuals at risk and can provide insights into the molecular basis of disease. Analysis of T2D in domestic animals provides both the opportunity to improve veterinary management and breeding programs as well as to identify novel T2D risk genes. Australian-bred Burmese (ABB) cats have a 4-fold increased incidence of type 2 diabetes (T2D) compared to Burmese cats bred in the United States. This is likely attributable to a genetic founder effect. We investigated this by performing a genome-wide association scan on ABB cats. Four SNPs were associated with the ABB T2D phenotype with p values <0.005. All exons and splice junctions of candidate genes near significant single-nucleotide polymorphisms (SNPs) were sequenced, including the genes DGKG, IFG2BP2, SLC8A1, E2F6, ETV5, TRA2B and LIPH . Six candidate polymorphisms were followed up in a larger cohort of ABB cats with or without T2D and also in Burmese cats bred in America, which exhibit low T2D incidence. The original SNPs were confirmed in this cohort as associated with the T2D phenotype, although no novel coding SNPs in any of the seven candidate genes showed association with T2D. The identification of genetic markers associated with T2D susceptibility in ABB cats will enable preventative health strategies and guide breeding programs to reduce the prevalence of T2D in these cats.

Campylobacter coli and Campylobacter jejuni are responsible for 400 million to 500 million cases of enteric disease each year and represent the most common cause of bacterial gastroenteritis worldwide. Despite its global importance, Campylobacter vaccine development has been hampered by the lack of animal models that recapitulate human disease pathogenesis. Here, we describe a naturally occurring Campylobacter -associated diarrhea model in outdoor-housed rhesus macaques. Using this model, we developed novel next-generation H 2 O 2 -based Campylobacter vaccines that induced strong antibacterial antibodies to multiple Campylobacter proteins including flagellin and provided up to 83% protection against severe C. coli -associated diarrhea. Whole-genome sequencing of circulating Campylobacter strains revealed little to no homology within lipooligosaccharide or capsular polysaccharide loci with the Campylobacter vaccine strains used in these studies, indicating that vaccine-mediated immunity was not restricted to a single homologous serotype. Together, these results demonstrate an important advance in vaccine development and a new approach to reducing Campylobacter -associated enteric disease., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

The exposure to toxic environmental and pharmaceutical substances can pose a long-term risk to human's health. In this study, we sought to investigate the potential of our recently developed method for induction of myeloid hematoendothelial and blood cells by overexpression of two transcription factors, GATA2 and ETV2, in human induced pluripotent stem cells (hiPSCs) for toxicity screening. For the primary screen in a high-throughput format, we selected twenty-two chemicals with various degrees of cytotoxicity available from the NIEHS National Toxicology Program (Tox21). The compounds were applied during the endothelial-to-hematopoietic transition and to differentiated myeloid progenitors growing in suspension. The system was capable of identifying compounds with both inhibitory and favorable effects on hematopoietic network, changes in expression of hematopoietic markers, and mitochondrial and cytotoxicity. The findings were confirmed and further investigated by secondary screens, colony forming cell assay, and gene expression profiling. The hematoendothelial toxicity of 5-fluorouracil, berberine chloride, and benzo(a)pyrene is characterized by the inhibition of cell division and a shift of hematopoietic programming to non-hemogenic endothelial and mesenchymal fates. This study demonstrates the feasibility of transcription factor (TF)-based differentiation systems to monitor endothelial and hematotoxicity and serves as an informative platform for screening myelosuppressive or stimulatory drugs and mechanistic studies of their action., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Diarrhea is the second leading cause of death in children under 5 years of age. Enhanced understanding of causal pathways, pathogenesis, and sequelae of diarrhea is urgently needed. Although the gut microbiota is believed to play a role in susceptibility to diarrheal diseases, our understanding of this association remains incomplete. Infant rhesus macaques (Macaca mulatta) are susceptible to diarrhea making them an ideal model to address this question., Results: The maturation of the infant rhesus macaque gut microbiome throughout the first 8 months of life occurs in a similar pattern as that described for human infants. Moreover, the microbiome of the captive reared infant rhesus macaque more closely resembles that of human infants in the developing world than in the western world. Importantly, prior to disease onset, the gut microbiome of infants that later develop diarrhea is enriched in pathways of immunomodulatory metabolite synthesis, while those of infants that remain asymptomatic are enriched in pathways for short-chain fatty acid production. We identify Prevotella strains that are more abundant at 1 month in infants that later develop diarrhea. At 8 months, the microbiomes of animals that experience diarrhea show increased abundance of Campylobacter and a reduction in Helicobacter macacae., Conclusion: The composition of the microbial community could provide a phenotypic marker of an infant's susceptibility to diarrheal disease. Given the significant physiological and immunological similarities between human and nonhuman primates, these findings provide potential markers of susceptibility to diarrhea that could be modulated to improve infant health, especially in the developing world.

Objectives: The purpose of hospital discharge instructions (HDIs) is to facilitate safe patient transitions home, but electronic health records can generate lengthy documents filled with irrelevant information. When our institution changed electronic health records, a cumbersome electronic discharge workflow produced low-value HDI and contributed to a spike in discharge delays. Our aim was to decrease these delays while improving family and provider satisfaction with HDI., Methods: We used quality improvement methodology to redesign the electronic discharge navigator and HDI to address the following issues: (1) difficulty preparing discharge instructions before time of discharge, (2) suboptimal formatting of HDI, (3) lack of standard templates and language within HDI, and (4) difficulties translating HDI into non-English languages. Discharge delays due to HDI were tracked before and after the launch of our new discharge workflow. Parents and providers evaluated HDI and the electronic discharge workflow, respectively, before and after our intervention. Providers audited HDI for content., Results: Discharge delays due to HDI errors decreased from a mean of 3.4 to 0.5 per month after our intervention. Parents' ratings of how understandable our HDIs were improved from 2.35 to 2.74 postintervention ( P = .05). Pediatric resident agreement that the electronic discharge process was easy to use increased from 9% to 67% after the intervention ( P < .001)., Conclusions: Through multidisciplinary collaboration we facilitated advance preparation of more standardized HDI and decreased related discharge delays from the acute care units at a large tertiary care hospital., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Background: Eye movement desensitization and reprocessing (EMDR) is recommended for post-traumatic stress disorder and emerging evidence indicates that it is effective for people with intellectual disabilities. However, acceptability from the perspectives of clients with intellectual disabilities, their therapists and other key people has not been formally evaluated. This study investigates process issues in the implementation of EMDR from perspectives of multiple stakeholders., Method: Semi-structured interviews were conducted with two adults with intellectual disabilities and three clinical psychologists who had participated in EMDR as well as a key supporter (N = 6) to provide information relating to three cases. The interviews were analysed thematically either directly from the audio recording or from transcripts., Results: Five themes were identified: EMDR feels very different; EMDR is a technical process; the need to work with the present; talking is important; cautious optimism., Conclusions: Whilst a range of client- and therapist-related factors served as barriers to using EMDR in this small-scale study, such as preferences in working with the present and inexperienced therapists, there was cautious optimism that EMDR may be useful for "the right person at the right time."., (© 2019 John Wiley & Sons Ltd.)

Importance: Numerous studies have demonstrated that long-term outcomes after orthopedic trauma are associated with psychosocial and behavioral health factors evident early in the patient's recovery. Little is known about how to identify clinically actionable subgroups within this population., Objectives: To examine whether risk and protective factors measured at 6 weeks after injury could classify individuals into risk clusters and evaluate whether these clusters explain variations in 12-month outcomes., Design, Setting, and Participants: A prospective observational study was conducted between July 16, 2013, and January 15, 2016, among 352 patients with severe orthopedic injuries at 6 US level I trauma centers. Statistical analysis was conducted from October 9, 2017, to July 13, 2018., Main Outcomes and Measures: At 6 weeks after discharge, patients completed standardized measures for 5 risk factors (pain intensity, depression, posttraumatic stress disorder, alcohol abuse, and tobacco use) and 4 protective factors (resilience, social support, self-efficacy for return to usual activity, and self-efficacy for managing the financial demands of recovery). Latent class analysis was used to classify participants into clusters, which were evaluated against measures of function, depression, posttraumatic stress disorder, and self-rated health collected at 12 months., Results: Among the 352 patients (121 women and 231 men; mean [SD] age, 37.6 [12.5] years), latent class analysis identified 6 distinct patient clusters as the optimal solution. For clinical use, these clusters can be collapsed into 4 groups, sorted from low risk and high protection (best) to high risk and low protection (worst). All outcomes worsened across the 4 clinical groupings. Bayesian analysis shows that the mean Short Musculoskeletal Function Assessment dysfunction scores at 12 months differed by 7.8 points (95% CI, 3.0-12.6) between the best and second groups, by 10.3 points (95% CI, 1.6-20.2) between the second and third groups, and by 18.4 points (95% CI, 7.7-28.0) between the third and worst groups., Conclusions and Relevance: This study demonstrates that during early recovery, patients with orthopedic trauma can be classified into risk and protective clusters that account for a substantial amount of the variance in 12-month functional and health outcomes. Early screening and classification may allow a personalized approach to postsurgical care that conserves resources and targets appropriate levels of care to more patients.

Background: The immune-mediated destruction of hematopoietic stem cells is implicated in the pathophysiology of aplastic anemia (AA). Immunosuppressive therapy (IST) using antithymocyte globulin and cyclosporine is successful in this setting. Eltrombopag is active in patients with refractory AA, presumably by increasing the bone marrow progenitors., Methods: This phase 2 trial initially was designed to evaluate standard IST in newly diagnosed patients with severe AA and later was amended to add eltrombopag to simultaneously address immune destruction and stem cell depletion. The primary outcome was the overall response rate (ORR) at 3 months and 6 months., Results: A total of 38 patients were enrolled: 17 (45%) received IST alone and 21 (55%) received additional eltrombopag. The ORR was 74%. Patients receiving IST plus eltrombopag had a similar ORR (76% vs 71%; P = .72), complete remission rate (38% vs 29%; P = .73), and median time to response (84 days vs 57 days; P = .30) compared with those receiving IST alone. The 2-year overall survival rate in the IST group was 91% compared with 82% for those patients treated with IST plus eltrombopag (P = .82). No cumulative toxicities were noted after the addition of eltrombopag., Conclusions: The addition of eltrombopag to standard IST was well tolerated and resulted in similar responses., (© 2018 American Cancer Society.)

The well-being of mothers and infants is influenced by mothers' behavioral and psychosocial health (B&PH), yet it is often neglected during healthcare visits. To address this gap, this study aimed to develop and evaluate acceptability of a postpartum toolkit (screening questionnaire, feedback template, and decision aid) to promote B&PH. Using a decision-making model and participatory design (N = 24), a B&PH screening questionnaire was refined, and prototypes of feedback templates and decision aids for selecting health goals were developed. Most mothers in this multi-ethnic sample rated the resulting toolkit as easy to understand/use and useful, and reported they were likely to act on their health goals. Toolkit ease of use and usefulness ratings were largely unrelated to education, ethnicity, and acculturation. In conclusion, findings support the toolkit's acceptability and applicability to women of diverse backgrounds. The toolkit is a promising strategy to engage mothers in setting goals to promote B&PH.

Background and Aims: Dysphagia is a debilitating symptom in patients with inoperable esophageal cancer that contributes to poor quality of life and worsening nutritional status. The 2 most commonly used palliative modalities for dysphagia are radiation therapy and esophageal stent placement. However, radiation therapy is limited by adverse events (AEs) and total dose, and stent placement has a high rate of AEs, including reflux, migration, and chest pain. A relatively new modality of liquid nitrogen endoscopic spray cryotherapy has been described as salvage when other options have been exhausted and when patients are no longer receiving systemic therapy. We evaluated the safety and efficacy of cryotherapy as the primary modality for relieving dysphagia in inoperable esophageal cancer including patients receiving systemic cancer therapy., Methods: This is a retrospective, multicenter, consecutive case series of 49 inoperable esophageal cancer patients undergoing palliative endoscopic cryotherapy at 4 specialized cancer centers from May 2014 to May 2016. The primary outcomes were change in dysphagia scores between pre- and postcryotherapy and AEs. Dysphagia was measured using a 5-point Likert scale: 0, no dysphagia; 1, dysphagia to solids; 2, dysphagia to semisolids; 3, dysphagia to liquids; 4, dysphagia to saliva., Results: Thirty-nine men and 10 women with a mean age of 58 years underwent a total of 120 cryotherapy treatments. The mean dysphagia score improved significantly from 2.4 precryotherapy to 1.7 postcryotherapy (improvement of .7 points; P < .001). Minor AEs were seen in 6 of 120 (5.0%) cryotherapy treatments (1 intraprocedural and 5 postprocedural). In addition, 1 patient developed a severe intraprocedural AE of dilation-related perforation, whereas another patient developed a benign stricture requiring dilation., Conclusions: This preliminary retrospective study suggests that liquid nitrogen spray cryotherapy may be safe and effective for dysphagia palliation in inoperable esophageal cancer. Large prospective studies are needed to confirm these findings and identify patient and procedure characteristics associated with the greatest benefit., (Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Ipilimumab, cytotoxic T-lymphocyte-associated protein 4-blocking antibody, is known to precipitate tissue-specific immune-related adverse events. The second most common site for immune-related adverse events is the gastrointestinal tract, with toxic injury resulting in diarrhea, colitis, and enterocolitis. In the present case, a woman who received ipilimumab 2 weeks prior was found to have severe, diffuse corticosteroid-refractory gastrointestinal tract toxic injury affecting the stomach, small bowel, and colon.

Objective: Guided by the Uses and Gratifications approach, to examine mothers' use and preference of e-Health media, and associated contextual factors., Design and Sample: Cross-sectional survey of 165 mothers (White, African-American, and Hispanic) from a stratified random sample., Measures: Use of online media about mother-baby care; favorite websites about motherhood and best-liked features of Web sites; channel preferences (Web site, postal mail, text) for receiving three types of health information; and contextual factors, e.g., education., Results: Media use ranged from 96% for health information searches about babies to 46% for YouTube viewing about mother-baby topics. Contextual factors, such as education, were associated with media use. Babycenter was the most frequently reported favorite Web site and rich, relevant information was the best-liked feature. Across three health topics (weight, stress/depression, parenting) mothers preferred receiving information by Web site, followed by postal mail and least by text messaging (χ 2 statistics, p < .001). Stress and race/ethnicity were among factors associated with preferences., Conclusions: Mothers widely used e-Health related media, but use was associated with contextual factors. In public health efforts to reach new mothers, partnering with mother-favored Web sites, focusing on audience-relevant media, and adopting attributes of successful sites are recommended strategies., (© 2017 Wiley Periodicals, Inc.)

This article examines the development, implementation, and evaluation of a pilot project utilizing high-fidelity simulation (HFS) to improve frontline staff members' confidence and skills to communicate about death and dying in long-term care homes. The target group was unregulated care providers who provide palliative care for residents and their families. Eighteen participants engaged in the educational intervention and evaluation. Results supported the effectiveness of HFS as an educational tool for unregulated health care providers. Quantitative data showed statistically significant improvements in participants' self-efficacy scores related to communicating about death and dying and end-of-life care. Qualitative data indicated that the experience was a valuable learning opportunity and helped participants develop insights into their own values, beliefs, and fears providing end-of-life care. HFS is therefore recommended as an innovative training strategy to improve palliative care communication in long-term care homes., (© The Author(s) 2015.)

Introduction: The introduction of major trauma centres (MTCs) in England has led to 63% reduction in trauma mortality.(1) The role of plastic surgeons supporting these centres has not been quantified previously. This study aimed to quantify plastic surgical workload at an urban MTC to determine the contribution of plastic surgeons to major trauma care., Methods: All Trauma Audit and Research Network (TARN)-recorded major trauma patients who presented to an urban MTC in 2013 and underwent an operation were identified retrospectively. Patients who underwent plastic surgery were identified and the type and date of procedure(s) were recorded. The trauma operative workload data of another tertiary surgical specialty and local historical plastics workload data from pre-MTC go-live were collected for comparison., Results: Of the 416 major trauma patients who required surgical intervention, 29% (n = 122) underwent plastic surgery. Of these patients, 43% had open lower limb fractures, necessitating plastic surgical involvement according to British Orthopaedic Association Standards for Trauma (BOAST) 4 guidance. The overall plastic surgery operative workload increased sevenfold post-MTC go-live. A similar proportion of the same cohort required neurosurgery (n = 115; p = 0.589)., Discussion: This study quantifies plastic surgery involvement in major trauma and demonstrates that plastic surgical operative workload is at least on par with other tertiary surgical specialties. It also reports one centre's experience of a significant change in plastic surgery activity following designation of MTC status. The quantity of plastic surgical operative workload in major trauma must be considered when planning major trauma service design and workforce provision, and for plastic surgical postgraduate training., (Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

High-resolution genetic and physical maps are invaluable tools for building accurate genome assemblies, and interpreting results of genome-wide association studies (GWAS). Previous genetic and physical maps anchored good quality draft assemblies of the domestic cat genome, enabling the discovery of numerous genes underlying hereditary disease and phenotypes of interest to the biomedical science and breeding communities. However, these maps lacked sufficient marker density to order thousands of shorter scaffolds in earlier assemblies, which instead relied heavily on comparative mapping with related species. A high-resolution map would aid in validating and ordering chromosome scaffolds from existing and new genome assemblies. Here, we describe a high-resolution genetic linkage map of the domestic cat genome based on genotyping 453 domestic cats from several multi-generational pedigrees on the Illumina 63K SNP array. The final maps include 58,055 SNP markers placed relative to 6637 markers with unique positions, distributed across all autosomes and the X chromosome. Our final sex-averaged maps span a total autosomal length of 4464 cM, the longest described linkage map for any mammal, confirming length estimates from a previous microsatellite-based map. The linkage map was used to order and orient the scaffolds from a substantially more contiguous domestic cat genome assembly (Felis catus v8.0), which incorporated ∼20 × coverage of Illumina fragment reads. The new genome assembly shows substantial improvements in contiguity, with a nearly fourfold increase in N50 scaffold size to 18 Mb. We use this map to report probable structural errors in previous maps and assemblies, and to describe features of the recombination landscape, including a massive (∼50 Mb) recombination desert (of virtually zero recombination) on the X chromosome that parallels a similar desert on the porcine X chromosome in both size and physical location., (Copyright © 2016 Li et al.)

Primary Objective: To review the prognosis of patients with bilateral fixed and dilated pupils secondary to traumatic extradural (epidural) or subdural haematoma who undergo surgery., Methods: A systematic review and meta-analysis was performed using random effects models. The Cochrane Central Register of Controlled Trials and PubMed databases were searched to identify relevant publications. Eligible studies were publications that featured patients with bilateral fixed and dilated pupils who underwent surgical evacuation of traumatic extra-axial haematoma, and reported on the rate of favourable outcome (Glasgow Outcome Score 4 or 5)., Results: Five cohort studies met the inclusion criteria, collectively reporting the outcome of 82 patients. In patients with extradural haematoma, the mortality rate was 29.7% (95% CI 14.7% to 47.2%) with a favourable outcome seen in 54.3% (95% CI 36.3% to 71.8%). In patients with acute subdural haematoma, the mortality rate was 66.4% (95% CI 50.5% to 81.9%) with a favourable outcome seen in 6.6% (95% CI 1.8% to 14.1%)., Conclusions and Implications of Key Findings: Despite the poor overall prognosis of patients with closed head injury and bilateral fixed and dilated pupils, our findings suggest that a good recovery is possible if an aggressive surgical approach is taken in selected cases, particularly those with extradural haematoma., Trial Registration Number: CRD42013005198., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Nutrient intake is often measured with substantial error both in commonly used surrogate instruments such as a food frequency questionnaire (FFQ) and in gold standard-type instruments such as a diet record (DR). If there is a correlated error between the FFQ and DR, then standard measurement error correction methods based on regression calibration can produce biased estimates of the regression coefficient (λ) of true intake on surrogate intake. However, if a biomarker exists and the error in the biomarker is independent of the error in the FFQ and DR, then the method of triads can be used to obtain unbiased estimates of λ, provided that there are replicate biomarker data on at least a subsample of validation study subjects. Because biomarker measurements are expensive, for a fixed budget, one can use a either design where a large number of subjects have one biomarker measure and only a small subsample is replicated or a design that has a smaller number of subjects and has most or all subjects validated. The purpose of this paper is to optimize the proportion of subjects with replicated biomarker measures, where optimization is with respect to minimizing the variance of ln(λ̂). The methodology is illustrated using vitamin C intake data from the European Prospective Investigation into Cancer and Nutrition study where plasma vitamin C is the biomarker. In this example, the optimal validation study design is to have 21% of subjects with replicated biomarker measures., (Copyright © 2014 John Wiley & Sons, Ltd.)

Background: As genome-wide sequence analyses for complex human disease determinants are expanding, it is increasingly necessary to develop strategies to promote discovery and validation of potential disease-gene associations., Findings: Here we present a dynamic web-based platform - GWATCH - that automates and facilitates four steps in genetic epidemiological discovery: 1) Rapid gene association search and discovery analysis of large genome-wide datasets; 2) Expanded visual display of gene associations for genome-wide variants (SNPs, indels, CNVs), including Manhattan plots, 2D and 3D snapshots of any gene region, and a dynamic genome browser illustrating gene association chromosomal regions; 3) Real-time validation/replication of candidate or putative genes suggested from other sources, limiting Bonferroni genome-wide association study (GWAS) penalties; 4) Open data release and sharing by eliminating privacy constraints (The National Human Genome Research Institute (NHGRI) Institutional Review Board (IRB), informed consent, The Health Insurance Portability and Accountability Act (HIPAA) of 1996 etc.) on unabridged results, which allows for open access comparative and meta-analysis., Conclusions: GWATCH is suitable for both GWAS and whole genome sequence association datasets. We illustrate the utility of GWATCH with three large genome-wide association studies for HIV-AIDS resistance genes screened in large multicenter cohorts; however, association datasets from any study can be uploaded and analyzed by GWATCH.

Comparative studies on community phylogenetics and phylogeography of microorganisms living in extreme environments are rare. Terrestrial subsurface habitats are valuable for studying microbial biogeographical patterns due to their isolation and the restricted dispersal mechanisms. Since the taxonomic identity of a microorganism does not always correspond well with its functional role in a particular community, the use of taxonomic assignments or patterns may give limited inference on how microbial functions are affected by historical, geographical and environmental factors. With seven metagenomic libraries generated from fracture water samples collected from five South African mines, this study was carried out to (1) screen for ubiquitous functions or pathways of biogeochemical cycling of CH4, S, and N; (2) to characterize the biodiversity represented by the common functional genes; (3) to investigate the subsurface biogeography as revealed by this subset of genes; and (4) to explore the possibility of using metagenomic data for evolutionary study. The ubiquitous functional genes are NarV, NPD, PAPS reductase, NifH, NifD, NifK, NifE, and NifN genes. Although these eight common functional genes were taxonomically and phylogenetically diverse and distinct from each other, the dissimilarity between samples did not correlate strongly with geographical or environmental parameters or residence time of the water. Por genes homologous to those of Thermodesulfovibrio yellowstonii detected in all metagenomes were deep lineages of Nitrospirae, suggesting that subsurface habitats have preserved ancestral genetic signatures that inform the study of the origin and evolution of prokaryotes.

Background: Safe patient transfer from hospitals to skilled nursing facilities (SNFs) is one of the most logistically challenging safety problems in the US medical system., Problem: The authors describe a community that experienced inefficient transfers in the 1990s, spurring development of continuous quality improvement (CQI) methods to develop transfer forms and processes to improve efficiency., Methods: The community established a Geriatric Forum for educational and process improvement purposes. Attendees consist of anyone involved with care of older patients in the community. Over the years, minor environmental changes forced periodic adjustments to transfer processes. The need for adjustment is identified by asking the simple question, "Have any problems occurred with transfers lately?" When problems are identified, forum attendees make process changes. The current forms and processes are discussed in detail., Results: Initial improvement in efficiency of transfers also produced improvements in patient safety and quality of medical care according to periodic internal surveys. During 2009, this community's 30-day rehospitalization rate of patients discharged to a SNF was 14.75%, lower than any national or state average reported rate., Conclusions: Developing hospital-to-SNF transfer methods focusing on the traditional CQI goals of efficiency, patient safety, and quality of care also yields lower hospital readmission rates. Because the methodology is that of CQI, a widely taught skill, similar programs could be established between any hospital and the SNFs to which it discharges patients. The particular examples of transfer forms and processes described might be helpful to other programs., (Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.)

We present theoretical results of a low-loss all-optical switch based on electromagnetically induced transparency and the quantum Zeno effect in a microdisk resonator. We show that a control beam can modify the atomic absorption of the evanescent field which suppresses the cavity field buildup and alters the path of a weak signal beam. We predict more than 35 dB of switching contrast with less than 0.1 dB loss using just 2 μW of control-beam power for signal beams with less than single photon intensities inside the cavity.

Rapid detection of nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) followed by appropriate infection control procedures reduces MRSA infection and transmission. We compared the performance and workflow of two Food and Drug Administration-approved nucleic acid amplification assays, the LightCycler MRSA Advanced Test and the Xpert MRSA test, with those of directly plated culture (MRSASelect) using 1202 nasal swabs collected at three U.S. sites. The sensitivity of the LightCycler test (95.2%; 95% CI, 89.1% to 98.4%) and Xpert assay (99%; 95% CI, 94.8% to 100%) did not differ compared with that of culture; the specificity of the two assays was identical (95.5%; 95% CI, 94.1% to 96.7%) compared with culture. However, sequencing performed on 71 samples with discordant results among the three methods confirmed the presence of MRSA in 40% of samples that were positive by both molecular methods but negative by culture. Workflow analysis from all sites including batch runs revealed average hands-on sample preparation times of 1.40, 2.35, and 1.44 minutes per sample for the LightCycler, Xpert, and MRSASelect methods, respectively. Discrete event simulation analysis of workflow efficiencies revealed that the LightCycler test used less hands-on time for the assay when greater than eight batched samples were run. The high sensitivity and specificity, low hands-on time, and efficiency gains using batching capabilities make the LightCycler test suitable for rapid batch screening of MRSA colonization., (Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Retinol is one of the most biologically active forms of vitamin A and is hypothesized to influence a wide range of human diseases including asthma, cardiovascular disease, infectious diseases and cancer. We conducted a genome-wide association study of 5006 Caucasian individuals drawn from two cohorts of men: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We identified two independent single-nucleotide polymorphisms associated with circulating retinol levels, which are located near the transthyretin (TTR) and retinol binding protein 4 (RBP4) genes which encode major carrier proteins of retinol: rs1667255 (P =2.30× 10(-17)) and rs10882272 (P =6.04× 10(-12)). We replicated the association with rs10882272 in RBP4 in independent samples from the Nurses' Health Study and the Invecchiare in Chianti Study (InCHIANTI) that included 3792 women and 504 men (P =9.49× 10(-5)), but found no association for retinol with rs1667255 in TTR among women, thus suggesting evidence for gender dimorphism (P-interaction=1.31× 10(-5)). Discovery of common genetic variants associated with serum retinol levels may provide further insight into the contribution of retinol and other vitamin A compounds to the development of cancer and other complex diseases.

In genome-wide association studies (GWAS) of common genetic variants associated with circulating alpha- and gamma-tocopherol concentrations in two adult cohorts comprising 5006 men of European descent, we observed three loci associated with alpha-tocopherol levels, two novel single-nucleotide polymorphisms (SNPs), rs2108622 on 19pter-p13.11 (P= 1.7 × 10(-8)) and rs11057830 on 12q24.31 (P= 2.0 × 10(-8)) and confirmed a previously reported locus marked by rs964184 on 11q23.3 (P= 2.7 × 10(-10)). The three SNPs have been reported to be associated with lipid metabolism and/or regulation. We replicated these findings in a combined meta-analysis with two independent samples, P= 7.8 × 10(-12) (rs964184 on 11q23.3 near BUD13, ZNF259 and APOA1/C3/A4/A5), P= 1.4 × 10(-10) (rs2108622 on 19pter-p13.11 near CYP4F2) and P= 8.2 × 10(-9) (rs11057830 on 12q24.31 near SCARB1). Combined, these SNPs explain 1.7% of the residual variance in log alpha-tocopherol levels. In one of the two male GWAS cohorts (n= 992), no SNPs were significantly associated with gamma-tocopherol concentrations after including data from the replication sample for 71 independent SNPs with P< 1 × 10(-4) identified.

This community's utilization of their Medical Reserve Corps (MRC) unit proved to be a valuable resource in their vaccination clinics as part of their response to the novel influenza A (H1N1) virus. Early planning, mock vaccination drills, and use of a strategic analysis process aided in the formulation and development of an efficient vaccination campaign.

The host genetic basis of differential outcomes in HIV infection, progression, viral load set point and highly active retroviral therapy (HAART) responses was examined for the common Y haplogroups in European Americans and African Americans. Accelerated progression to acquired immune deficiency syndrome (AIDS) and related death in European Americans among Y chromosome haplogroup I (Y-I) subjects was discovered. Additionally, Y-I haplogroup subjects on HAART took a longer time to HIV-1 viral suppression and were more likely to fail HAART. Both the accelerated progression and longer time to viral suppression results observed in haplogroup Y-I were significant after false-discovery-rate corrections. A higher frequency of AIDS-defining illnesses was also observed in haplogroup Y-I. These effects were independent of the previously identified autosomal AIDS restriction genes. When the Y-I haplogroup subjects were further subdivided into six I subhaplogroups, no one subhaplogroup accounted for the effects on HIV progression, viral load or HAART response. Adjustment of the analyses for population stratification found significant and concordant haplogroup Y-I results. The Y chromosome haplogroup analyses of HIV infection and progression in African Americans were not significant. Our results suggest that one or more loci on the Y chromosome found on haplogroup Y-I have an effect on AIDS progression and treatment responses in European Americans.

Background and Purpose: Hemodynamics is thought to play an important role in the mechanisms of cerebral aneurysm initiation, progression, and rupture. The purpose of this study was to present a hemodynamic study of a cerebral aneurysm immediately before its rupture to assess whether previously identified hemodynamic characteristics would classify this aneurysm in the high-risk category., Materials and Methods: A patient-specific computational fluid dynamics model was constructed from 3D rotational angiographic images acquired just hours before the aneurysm had ruptured. A pulsatile flow simulation was carried out, and the hemodynamics characterized by the concentration of the inflow jet, the size of the flow impingement region, and the complexity and stability of the flow pattern., Results: We found that the aneurysm had a concentrated inflow jet that impacted onto a small region of the dome of the aneurysm and created a complex, unstable flow pattern., Conclusions: This study supports the proposition that hemodynamic characteristics derived from image-based computational models can be used to identify cerebral aneurysms at high risk for rupture.

Reducing inconsistency and variability in emergency care processes increases chances for survival. Development of consistent processes for early risk stratification of patients with acute coronary syndrome and provision of evidence-based therapy will reduce variability. A reproducible system of care for patients with acute coronary syndrome was developed. Results show that the current mean time to electrocardiogram was 9 minutes. The percent of patients receiving aspirin within 24 hours of arrival was 96%. Average door-to-reperfusion time was less than 90 minutes in 55% of patients. Reperfusion was accomplished by percutaneous coronary intervention for 92% of patients. Mortality for patients experiencing an acute myocardial infarction decreased 30%, from 8.9% in fiscal year 2003 to 6.2% in fiscal year 2007.

The National Association of County and City Health Officials (NACCHO) is the national organization representing local health departments. NACCHO supports efforts that protect and improve the health of all people and all communities by promoting national policy, developing resources and programs, seeking health equity, and supporting effective local public health practice and systems.

Underreporting of energy intake in diet recalls is common, especially among obese individuals. Incentives have been used to ameliorate the problem, but are typically provided without efficacy assessment. The present study sought to determine whether financial incentives decrease underreporting in diet recalls. Three groups were used to assess incentive timing effects in this parallel group crossover study. One group received a $50 bonus for accurate diet recalls on the first two of four recalls. Accuracy was purportedly verified by salivary analysis. Another group received the $50 bonus for the last two recalls. A third group received no incentive. Mean energy intake during the first two visits was compared to mean energy intake during the last two visits to assess differences resulting from the incentive. Underreporters were identified using a Goldberg cutoff and energy intake <76% of estimated energy expenditure. Energy intake did not differ within or between groups at any time, and the number of underreporters was not associated with group at any time. Overall, the incentive was ineffective in this small, homogeneous sample. Future studies should assess different forms of incentives, other study populations, and the probability of incentives causing undereating.

Background: In fall 2003 the five hospitals in Wichita, Kansas, formed a collaborative to improve care for patients presenting with acute myocardial infarction or heart failure (HF). Standard order sets were developed from guidelines developed by the American College of Cardiology and the American Heart Association. THE WICHITA CITYWIDE HEART CARE COLLABORATIVE GETS TO WORK: The order sets, which highlighted the appropriate interventions and made their implementation a "checkbox" activity, were placed in the progress note section of the medical record. Booklets for patient education on heart care were developed., Results: All five hospitals have experienced significant improvement in core measure data. For example, for angiotension-converting enzyme inhibitor for left ventricular systolic dysfunction, the overall compliance score improved from 70% to 85%, a 15% improvement in 18 months. Compliance for HF was perhaps more successful, given the low level of initial compliance (50%)., Discussion: Physician compliance was enhanced by incorporating the guidelines into practitioners' daily workflow needs, providing prompt feedback on their performance, incorporating their suggestions made at the point of care, and using process measurements.

Studies that investigate infant and/or child development in families of depressed or anxious mothers do not include samples of foreign-born non-English-speaking mothers. This article describes a pilot study investigating infant development, maternal depression, and anxiety in comparison samples of native-born and foreign-born mothers and children from Vietnam, Laos (Hmong), and the Democratic Republic of Congo. Maternal depression and anxiety were measured with the Hopkins Symptom Checklist-25, and the developmental status of children 0-25 months of age was measured with the Denver II. Foreign-born mothers were more anxious than native-born mothers. Non-English-speaking foreign-born mothers were clinically depressed (1.83) and moderately anxious (1.62). Infants of native-born mothers and English-speaking foreign-born mothers performed better on the Denver II than children of foreign-born non-English-speaking mothers. Infants and toddlers of non-English-speaking mothers appear to be at high risk for delays during their first 25 months of life. Public health nurses need to advocate for appropriate interpreter services and mental health resources for non-English-speaking mothers of young children. Developmental screening should reflect cultural variations in parental expectations of how and when children meet developmental milestones. Replication studies and investigation about the long-term development of this high-risk group of children are needed.

The study determines the effectiveness of a sexuality-positive adolescent sexual offender treatment program and examines subsequent criminal recidivism in the three outcome groups (completed, withdrawn, referred). The sample consists of 122 adolescent males and their families (491 individuals). Of the demographic variables, only living situation was significant, such that patients living with parents were more likely to graduate. None of the behavioral variables were found to be significant. Of the treatment variables, length of time in the program and participation in the Family Journey Seminar were included in the final model. When they were included in the model, no other treatment variable were significantly related to probability of graduation. There were no arrests or convictions for sex-related crimes in the population of participants that successfully completed the program. This group was also less likely than the other groups to be arrested (p = 0.014) or convicted (p = 0.004) across all crime categories.

Mutations in the gene encoding thrombomodulin (TM), a thrombin regulator, are suspected risk factors for venous and arterial thrombotic disease. We have previously described the generation of TM(Pro/Pro) mice carrying a TM gene mutation that disrupts the TM-dependent activation of protein C. Here, it is shown that inbred C57BL/6J TM(Pro/Pro) mice exhibit a hypercoagulable state and an increased susceptibility to thrombosis and sepsis. Platelet thrombus growth after FeCl(3)-induced acute endothelial injury was accelerated in mutant mice. Vascular stasis after permanent ligation of the carotid artery precipitated thrombosis in mutant but not in normal mice. Mutant mice showed increased mortality after exposure to high doses of endotoxin and demonstrated altered cytokine production in response to low-dose endotoxin. The severity of the hypercoagulable state and chronic microvascular thrombosis caused by the TM(Pro) mutation is profoundly influenced by mouse strain-specific genetic differences between C57BL/6 and 129SvPas mice. These data demonstrate that in mice, TM is a physiologically relevant regulator of platelet- and coagulation-driven large-vessel thrombosis and modifies the response to endotoxin-induced inflammation. The phenotypic penetrance of the TM(Pro) mutation is determined by as-yet-uncharacterized genetic modifiers of thrombosis other than TM.

The thrombomodulin (TM) gene was ablated in mice in a cell type-restricted manner from vascular endothelium by Cre-recombinase-mediated excision controlled by the endothelial cell lineage-specific Tie2 promoter. Forty percent of mutant (TMLox-) mice display a distinct lethal embryonic phenotype not observed in completely TM-deficient embryos. The remaining 60% of TMLox mice survive beyond birth, but invariably succumb to a severe hypercoagulable state and massive thrombosis after 3 weeks, terminating in a lethal consumptive coagulopathy. The progression of thrombosis was age- and sex-dependent. Disruption of the TM/protein C pathway was not associated with a latent proinflammatory state. Disease onset and progression could be prevented by warfarin anticoagulation. These results show that in mice, loss of endothelial cell TM function causes spontaneous and fatal thrombosis in the arterial and venous circulation, resulting from unfettered activation of the coagulation system. The combination of complete disease penetrance, uniform disease onset at young age, large vessel thrombosis of the extremities and multiple organ systems, and consumptive coagulopathy as the disease end-point provides a unique mouse model of human thrombotic disease.

This article summarizes the results of a fungal investigation of a new, seven-story, 170-room hotel. The owners of the building were refused an occupancy permit by local building officials because of concerns about fungal contamination. This article discusses the processes that were used to investigate and abate the fungal concerns in this building. This investigation involved comparing fungal infestation levels in various building materials, including two different types of gypsum wallboard. During initial testing the indoor air concentrations of problematic fungi were up to 50 times higher than outdoor levels. After the removal of the fungal-infested materials and the replacement with more acceptable materials, the indoor air concentration of problematic fungi dropped to less than one-fourth of outdoor levels.

Murine gammaherpesvirus 68 (MHV68) is a gammaherpesvirus that was first isolated from murid rodents. MHV68 establishes a latent infection in the spleen and other lymphoid organs. Several gammaherpesviruses, including herpesvirus saimiri, human herpesvirus 8, and MHV68, encode proteins with extensive homology to the D-type cyclins. To study the function of the cyclin homologue, a recombinant MHV68 has been constructed that lacks the cyclin homologue and expresses beta-galactosidase as a marker (MHV68(cy-)). MHV68(cy-) grows in vitro with kinetics and to titers similar to those of the wild type. BALB/c mice infected with mixtures of equivalent amounts of the wild type and MHV68(cy-) show deficient growth of the MHV68(cy-) in an acute infection. Infection of SCID mice with virus mixtures also showed decreased MHV68(cy-) virus growth, indicating that the deficiency is not mediated by T or B cells. Although mice infected with mixtures containing 100 times as much MHV68(cy-) had greater splenic titers of the mutant virus than wild-type virus in acute infection, at 28 days postinfection splenocytes from these mice reactivated primarily wild-type virus. Quantitative PCR data indicate that equivalent genomes were present in the latent state. Reinsertion of the cyclin homologue into the cyclin-deleted virus restored the wild-type phenotype. These results indicate that the MHV68 cyclin D homologue mediates important functions in the acute infection and is required for efficient reactivation from latency.

Evaluation of a school-based, bicycle helmet program was conducted using the PRECEDE model. The intervention targeted schools with low income, high minority, and nonurban fourth grade children. A repeated measures design was used with schools randomly assigned to each treatment: classroom, parent-classroom, or control. Reported helmet use was approximately 18% prior to the program. Following the intervention, between 34% and 98% of intervention students reported helmet use, with the best results reported in schools with parental contact. This educational intervention coupled with the provision of bicycle helmets increased reported helmet use, especially when parental contact was added.

Background: Cytomegalovirus (CMV) has been associated with the development of chronic allograft rejection. Attempts to delineate pathogenetic mechanisms for this association have characteristically used well-established laboratory strains for in vitro investigation and rodent strains for in vivo studies. There is substantial genetic heterogeneity not only among different laboratory strains, but also between laboratory strains and clinical isolates, and genetic differences between human and animal strains are profound. Given these genetic differences, one would anticipate differences in biological activity between strains., Methods: Vascular endothelial cells were infected with two laboratory strains of CMV (Towne and AD-169) as well as two individual clinical CMV isolates, after genetic typing with six segments of the genome (including early and late genes). mRNA expression coding for a panel of mesenchymal growth factors was studied using quantitative reverse transcription, polymerase chain reaction. Major histocompatibility complex (MHC) expression was investigated using flow cytometry., Results: There was substantial genetic variability between clinical and laboratory isolates. There did not appear to be differences in overall infectivity by the different strains as determined by expression of immediate-early antigen at 24 hours (5-10% of endothelial cells positive for immediate-early. Two growth factors, platelet-derived growth factor-A and basic fibroblast growth factor were augmented by one of the two clinical strains of CMV (Clin 2) (P=0.0091 and P=0.0018, respectively). Transforming growth factor -alpha and insulin-like growth factor expression were significantly reduced by both clinical strains and AD-169. Two other growth factors, heparin-binding epidermal growth factor and transforming growth factor-beta were not altered by infection with any strain. No strain altered MHC class II expression. MHC class I expression was increased with one of the two clinical strains (Clin 1, P=0.0006) and decreased by AD-169 (P=0.0016). Clin 2 and Towne had no effect on MHC class I expression., Conclusions: These data demonstrate that the genetic heterogeneity of CMV is associated with differences in transplant-relevant biologic activity even among clinical isolates. The relationship between CMV and chronic rejection may be difficult to determine given the heterogeneous nature of this complex virus.