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John D Hong,1 Elliot H Choi,1 Susie Suh,1 Joseph H Bui,1 Annabelle M Storch,1 Kimberly R Walker,1 Kourosh Shahraki,1 Carolina Yanez,1 Diana Torres,1 Jennifer Espinoza,1 Iliana Molina,2,* Donny W Suh1,* 1Gavin Herbert Eye Institute, Department of Ophthalmology, University of California, Irvine, CA, USA; 2Shiley Eye Institute, Department of Ophthalmology, University of California, San Diego, CA, USA*These authors contributed equally to this workCorrespondence: Donny W Suh, Gavin Herbert Eye Institute, Department of Ophthalmology, University of California, Irvine, 850 Health Sciences Road, Irvine, CA, 92697, USA, Tel +1 949 824-4122, Email donnys@hs.uci.edu Iliana Molina, Shiley Eye Institute, Department of Ophthalmology, University of California, San Diego, 9415 Campus Point Dr, San Diego, CA, 92037, USA, Tel +1 858 822-2585, Email imolina@health.ucsd.eduPurpose: Uncorrected refractive errors (REs) and amblyopia can lead to visual impairment with deleterious effects on quality of life and academic performance. Early detection and treatment by community vision care programs, such as the UCI EyeMobile for Children, can aid in addressing preventable vision loss.Methods: A total of 5074 children between the ages of 3 and 10 years were screened at 153 locations, including preschools, head start programs, and elementary schools within Orange County (OC), California (CA). Subsequently, 1024 children presented for comprehensive eye examinations. A retrospective analysis of all examined children was conducted, determining the frequency and severity of REs and amblyopia and the spectacle prescription rate by age. Propensity score matching analysis evaluated the effect of median household income on RE and amblyopia frequency.Results: Among those who failed initial screening and were subsequently examined, significant rates of REs and amblyopia were detected: myopia (24.4%), hyperopia (35.4%), astigmatism (71.8%), anisometropia (8.9%), amblyopia (7.0%), and amblyopia risk (14.4%). A majority (65.0%) of those examined received prescription spectacles from UCI EyeMobile, with around a third requiring a new or updated prescription. The frequency of REs and amblyopia and the spectacle prescription rate were uniform across OC congressional districts. Myopia and amblyopia risk was positively and negatively associated with household income, respectively.Conclusion: The UCI EyeMobile for Children serves as a vital vision care program, providing free vision screening, comprehensive eye examinations, and spectacles. A significant number of children required examination, and a high frequency of REs and amblyopia were detected in examined children, with subsequent provision of prescription spectacles to most children.Keywords: pediatrics, refractive error, amblyopia, spectacles, mobile clinic, screening

OBJECTIVE: To investigate seven congenital myopathy patients from six families: one French Gypsy, one Spanish Gypsy, four British Pakistanis, and one British Indian. Three patients required mechanical ventilation from birth, five died before 22 months, one is ventilator-dependent, but one, at 30 months, is sitting with minimal support. All parents were unaffected. METHODS: The alpha-skeletal muscle actin gene (ACTA1) was sequenced. Available muscle biopsies were investigated by standard histological and electron microscopic techniques. The expression of various proteins was determined by immunohistochemistry, western blotting, or both. RESULTS: Three homozygous ACTA1 null mutations were identified: p.Arg41X in the French patient, p.Tyr364fsX in the Spanish patient, and p.Asp181fsX10 in all five British patients. An absence of alpha-skeletal muscle actin protein but presence of alpha-cardiac actin was shown in all muscle biopsies examined, with more alpha-cardiac actin in the biopsy from the child with the greatest muscle function. Muscle biopsies from all patients exhibited nemaline bodies whereas three also contained zebra bodies. INTERPRETATION: The seven patients have recessive nemaline myopathy caused by absence of alpha-skeletal muscle actin. The level of retention of alpha-cardiac actin, the skeletal muscle fetal actin isoform, may determine alpha-skeletal muscle actin disease severity. This has implications for possible future therapy. Ann Neurol 2006. [ABSTRACT FROM AUTHOR]

Purpose: To analyze referral rates, patient demographics, referral indications, and the impact of socioeconomic factors on ocular health from the University of California Irvine (UCI) Eye Mobile for Children, particularly during the coronavirus disease 2019 (COVID-19) pandemic., Methods: A retrospective chart review was performed on de-identified records of children examined on the UCI Eye Mobile. GraphPad Prism 10.0.0 and Python software were used for statistical analyses., Results: In the academic years from 2018 to 2022, 3,619 children received comprehensive eye examinations on the UCI Eye Mobile. Among them, 76 were referred to a pediatric ophthalmologist. The majority of these children were Hispanic (72.6%, 54 of 74), followed by Asian (10.9%, 8 of 74). A significant proportion (82.9%, 63 of 76) attended school districts with median incomes below that of Orange County. Statistically significant differences were found in age ( P = .001; pre-COVID: 3.98 ± 1.08 years vs COVID: 5.75 ± 2.92 years) and gender ( P = .023; pre-COVID female: 31 of 41 vs COVID female: 15 of 32) between the pre-COVID and COVID years. Additionally, there were significant differences in the proportion of children with hyperopia with astigmatism between the pre-COVID and COVID years ( P = .044; pre-COVID: 23 of 40 vs COVID: 12 of 35). The most common indications for ophthalmologist referrals were for strabismus evaluation/treatment (28.9%, 22 of 76), followed by abnormal cup-to-disc ratio (21.1%, 16 of 76)., Conclusions: The study highlights the pivotal role of the UCI Eye Mobile for children in identifying ocular conditions needing referrals to subspecialty care. The majority of children needing these referrals attended schools in lower economic communities. Additionally, the COVID-19 pandemic appears to have influenced the demographic and clinical characteristics. [ J Pediatr Ophthalmol Strabismus . 2024;61(5):309-316.] .

Understanding drivers of disease vectors' population dynamics is a pressing challenge. For short-lived organisms like mosquitoes, landscape-scale models must account for their highly local and rapid life cycles. Aedes aegypti, a vector of multiple emerging diseases, has become abundant in desert population centers where water from precipitation could be a limiting factor. To explain this apparent paradox, we examined Ae. aegypti abundances at > 660 trapping locations per year for 3 years in the urbanized Maricopa County (metropolitan Phoenix), Arizona, USA. We created daily precipitation layers from weather station data using a kriging algorithm, and connected localized daily precipitation to numbers of mosquitoes trapped at each location on subsequent days. Precipitation events occurring in either of two critical developmental periods for mosquitoes were correlated to suppressed subsequent adult female presence and abundance. LASSO models supported these analyses for female presence but not abundance. Precipitation may explain 72% of Ae. aegypti presence and 90% of abundance, with anthropogenic water sources supporting mosquitoes during long, precipitation-free periods. The method of using kriging and weather station data may be generally applicable to the study of various ecological processes and patterns, and lead to insights into microclimates associated with a variety of organisms' life cycles., (© 2024. The Author(s).)

Aedes aegypti is the primary vector of dengue virus and threatens 3.9 billion people living in many tropical and subtropical countries. Prevention and reduction of dengue and other Aedes-borne viruses, including Zika and chikungunya, requires control of mosquito populations. Community mobilization and input are essential components of vector control efforts. Many vector control campaigns do not engage communities prior to implementation, leading to program failure. Those that do often conduct basic knowledge, attitude, and practice surveys that are not designed to explicitly elicit preferences. Here, we applied a novel stated preference elicitation tool, best-worst choice, to understand preferences, willingness to participate, and willingness to pay for mosquito control in dengue-endemic communities of Peñuelas, Puerto Rico. Findings revealed that the community preferred mosquito control programs that are 1) applied at the neighborhood level, 2) implemented by the local government, and 3) focused specifically on reducing disease transmission (e.g., dengue) instead of mosquito nuisance. Programs targeting the reduction of disease transmission and higher educational level of participants increased willingness to participate. Participants were willing to pay an average of $72 annually to have a program targeting the reduction of diseases such as dengue. This study serves as a model to engage communities in the design of mosquito control programs and improve stakeholders' decision-making.

Significance: This pilot randomized trial, the first to evaluate a specific base-in relieving prism treatment strategy for childhood intermittent exotropia, did not support proceeding to a full-scale clinical trial. Defining and measuring prism adaptation in children with intermittent exotropia are challenging and need further study., Purpose: This study aimed to determine whether to proceed to a full-scale trial of relieving base-in prism spectacles versus refractive correction alone for children with intermittent exotropia., Methods: Children 3 years old to those younger than 13 years with distance intermittent exotropia control score of ≥2 points on the Intermittent Exotropia Office Control Scale (Strabismus 2006;14:147-150; 0 [phoria] to 5 [constant]), ≥1 episode of spontaneous exotropia, and 16 to 35∆ by prism-and-alternate-cover test, who did not fully prism adapt on a 30-minute in-office prism-adaptation test were randomized to base-in relieving prism (40% of the larger of distance and near exodeviations) or nonprism spectacles for 8 weeks. A priori criteria to conduct a full-scale trial were defined for the adjusted treatment group difference in mean distance control: "proceed" (≥0.75 points favoring prism), "uncertain" (>0 to <0.75 points favoring prism), or "do not proceed" (≥0 points favoring nonprism)., Results: Fifty-seven children (mean age, 6.6 ± 2.2 years; mean baseline distance control, 3.5 points) received prism (n = 28) or nonprism (n = 29) spectacles. At 8 weeks, mean control values were 3.6 and 3.3 points in prism (n = 25) and nonprism (n = 25) groups, respectively, with an adjusted difference of 0.3 points (95% confidence interval, -0.5 to 1.1 points) favoring nonprism (meeting our a priori "do not proceed" criterion)., Conclusions: Base-in prism spectacles, equal to 40% of the larger of the exodeviations at distance or near, worn for 8 weeks by 3- to 12-year-old children with intermittent exotropia did not yield better distance control than refractive correction alone, with the confidence interval indicating that a favorable effect of 0.75 points or larger is unlikely. There was insufficient evidence to warrant a full-scale randomized trial., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2023 American Academy of Optometry.)

Dengue transmission is determined by a complex set of interactions between the environment, Aedes aegypti mosquitoes, dengue viruses, and humans. Emergence in new geographic areas can be unpredictable, with some regions having established mosquito populations for decades without locally acquired transmission. Key factors such as mosquito longevity, temperature-driven extrinsic incubation period (EIP), and vector-human contact can strongly influence the potential for disease transmission. To assess how these factors interact at the edge of the geographical range of dengue virus transmission, we conducted mosquito sampling in multiple urban areas located throughout the Arizona-Sonora desert region during the summer rainy seasons from 2013 to 2015. Mosquito population age structure, reflecting mosquito survivorship, was measured using a combination of parity analysis and relative gene expression of an age-related gene, SCP-1. Bloodmeal analysis was conducted on field collected blood-fed mosquitoes. Site-specific temperature was used to estimate the EIP, and this predicted EIP combined with mosquito age were combined to estimate the abundance of "potential" vectors (i.e., mosquitoes old enough to survive the EIP). Comparisons were made across cities by month and year. The dengue endemic cities Hermosillo and Ciudad Obregon, both in the state of Sonora, Mexico, had higher abundance of potential vectors than non-endemic Nogales, Sonora, Mexico. Interestingly, Tucson, Arizona consistently had a higher estimated abundance of potential vectors than dengue endemic regions of Sonora, Mexico. There were no observed city-level differences in species composition of blood meals. Combined, these data offer insights into the critical factors required for dengue transmission at the ecological edge of the mosquito's range. However, further research is needed to integrate an understanding of how social and additional environmental factors constrain and enhance dengue transmission in emerging regions.

Background: The Aedes aegypti mosquito is a vector of several viruses including dengue, chikungunya, zika, and yellow fever. Vector surveillance and control are the primary methods used for the control and prevention of disease transmission; however, public health institutions largely rely on measures of population abundance as a trigger for initiating control activities. Previous research found evidence that at the northern edge of Ae. aegypti's geographic range, survival, rather than abundance, is likely to be the factor limiting disease transmission. In this study, we sought to test the utility of using body size as an entomological index to surveil changes in the age structure of field-collected female Aedes aegypti., Methods: We collected female Ae. aegypti mosquitoes using BG sentinel traps in three cities at the northern edge of their geographic range. Collections took place during their active season over the course of 3 years. Female wing size was measured as an estimate of body size, and reproductive status was characterized by examining ovary tracheation. Chronological age was determined by measuring transcript abundance of an age-dependent gene. These data were then tested with female abundance at each site and weather data from the estimated larval development period and adulthood (1 week prior to capture). Two sources of weather data were tested to determine which was more appropriate for evaluating impacts on mosquito physiology. All variables were then used to parameterize structural equation models to predict age., Results: In comparing city-specific NOAA weather data and site-specific data from HOBO remote temperature and humidity loggers, we found that HOBO data were more tightly associated with body size. This information is useful for justifying the cost of more precise weather monitoring when studying intra-population heterogeneity of eco-physiological factors. We found that body size itself was not significantly associated with age. Of all the variables measured, we found that best fitting model for age included temperature during development, body size, female abundance, and relative humidity in the 1 week prior to capture . The strength of models improved drastically when testing one city at a time, with Hermosillo (the only study city with seasonal dengue transmission) having the best fitting model for age. Despite our finding that there was a bias in the body size of mosquitoes collected alive from the BG sentinel traps that favored large females, there was still sufficient variation in the size of females collected alive to show that inclusion of this entomological indicator improved the predictive capacity of our models., Conclusions: Inclusion of body size data increased the strength of weather-based models for age. Importantly, we found that variation in age was greater within cities than between cities, suggesting that modeling of age must be made on a city-by-city basis. These results contribute to efforts to use weather forecasts to predict changes in the probability of disease transmission by mosquito vectors., (© 2022. The Author(s).)

Nonpathogenic bacteria likely play important roles in the biology and vector competence of ticks and other arthropods. Coxiella, a gram-negative gammaproteobacterium, is one of the most commonly reported maternally inherited endosymbionts in ticks and has been associated with over 40 tick species. Species-specific Coxiella-like endosymbionts (CLEs) have been reported in the brown dog tick, Rhipicephalus sanguineus sensu lato (Acari: Ixodidae), throughout the world, while recent research suggests low Coxiella diversity among tick species. We investigated CLE diversity among R. sanguineus s.l. ticks across Arizona. We detected 37 recurrent sequence variants (SVs) of the symbiont, indicating greater diversity in these symbiotic bacteria than previously reported. However, two SVs accounted for the vast majority of 16S rRNA amplicon reads. These two dominant CLEs were both closely related to Candidatus C. mudrowiae, an identified symbiont of Rhipicephalus turanicus ticks. One strain strongly associated with the tropical lineage of R. sanguineus s.l. while the other was found almost exclusively in the temperate lineage, supporting the conclusion that CLEs are primarily vertically transmitted. However, occasional mismatches between tick lineage and symbiont SV indicate that horizontal symbiont transfer may occur, perhaps via cofeeding of ticks from different lineages on the same dog. This study advances our understanding of CLE diversity in Rh. sanguineus s.l., (© The Author(s) 2022. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rhipicephalus sanguineus s.l. (Latreille, 1806), the brown dog tick, is the most widely distributed tick species in the world. The two dominant lineages, a temperate group and a tropical group, are recognized as important disease vectors for both dogs and humans. The temperate and tropical lineages overlap in range in some regions of the world, including the southwestern United States, where recent outbreaks of Rocky Mountain spotted fever are linked to R. sanguineus s.l. While it is unclear to what extent they may differ in their capacity to transmit pathogens, finer-scale resolution of temperate and tropical lineage distribution may provide insight into the ecology of these two tick groups and the epidemiology of R. sanguineus s.l.-vectored diseases. Using diagnostic polymerase chain reaction assays, we examined the geospatial trends in R. sanguineus s.l. lineages throughout Arizona. We found the temperate and tropical lineages were well delineated, with some overlap in the eastern part of the state. In one county, tropical and temperate ticks were collected on the same dog host, demonstrating that the two lineages are living in sympatry in some instances and may co-feed on the same host.

Background: There are reports of spinal cord injury (SCI) occurring after lower extremity (LE) surgery in children with mucopolysaccharidoses (MPS). Intraoperative neurological monitoring (IONM) has been adopted in some centers to assess real-time spinal cord function during these procedures. The aim of this investigation was to review 3 specialty centers' experiences with MPS patients undergoing LE surgery. We report how IONM affected care and the details of spinal cord injuries in these patients., Methods: All pediatric MPS patients who underwent LE surgery between 2001 and 2018 were reviewed at 3 children's orthopaedic specialty centers. Demographic and surgical details were reviewed. Estimated blood loss (EBL), surgical time, positioning, use of IONM, and changes in management as a result of IONM were recorded. Details of any spinal cord injuries were examined in detail., Results: During the study period, 92 patients with MPS underwent 252 LE surgeries. IONM was used in 83 of 252 (32.9%) surgeries, and intraoperative care was altered in 17 of 83 (20.5%) cases, including serial repositioning (n=7), aggressive blood pressure management (n=6), and abortion of procedures (n=8). IONM was utilized in cases with larger EBL (279 vs. 130 mL) and longer operative time (274 vs. 175 min) compared with procedures without IONM. Three patients without IONM sustained complete thoracic SCI postoperatively, all from cord infarction in the upper thoracic region. These 3 cases were characterized by long surgical time (328±41 min) and substantial EBL (533±416 mL or 30.5% of total blood volume; range, 11% to 50%). No LE surgeries accompanied by IONM experienced SCI., Conclusions: Patients with MPS undergoing LE orthopaedic surgery may be at risk for SCI, particularly if the procedures are long or are expected to have large EBL. One hypothesis for the etiology of SCI in this setting is hypoperfusion of the upper thoracic spinal cord due to prolonged intraoperative or postoperative hypotension. IONM during these procedures may mitigate the risk of SCI by identifying real-time changes in spinal cord function during surgery, inciting a change in the surgical plan., Level of Evidence: Level III-retrospective comparative series., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Rocky Mountain spotted fever (RMSF) is a serious disease in northwest Mexico, particularly in low-income communities. This study aimed to evaluate RMSF-related knowledge, attitudes, and practices in an endemic urban area with a high burden of the disease. A cross-sectional study design using a non-probabilistic household survey was conducted with 400 residents in Hermosillo, Mexico. Primary themes assessed included dog and tick-related exposure, RMSF knowledge, healthcare-seeking behavior, sociodemographic data, and household information. The majority (59%) of those surveyed had heard about RMSF, although only 36% of RMSF-aware respondents knew any RMSF symptoms. Among RMSF-aware respondents, 26% did not know or were unsure of prevention strategies. Individuals in the low socioeconomic status (SES) stratum were less likely to have heard about RMSF (odds ratio [OR]: 0.39; 95% CI: 0.25-0.59), use dog collars or any other product to avoid ticks (OR: 0.40; 95% CI: 0.17-0.99), or check their dogs for ticks (OR: 0.25; 95% CI: 0.09-0.74). The likelihood of observing high numbers of free-roaming dogs in their neighborhood was four times higher in the low SES stratum (OR: 4.19; 95% CI: 2.10-8.38) than in the high SES stratum. These findings emphasize the need for an integrative community approach to improve early recognition of symptoms and knowledge of prevention strategies, particularly in low SES neighborhoods.

The Aedes aegypti mosquito is the primary vector of dengue, yellow fever, chikungunya, and Zika viruses. Infection with the dengue virus alone occurs in an estimated 400 million people each year. Likelihood of infection with a virus transmitted by Ae. aegypti is most commonly attributed to abundance of the mosquito. However, the Arizona-Sonora desert region has abundant Ae. aegypti in most urban areas, yet local transmission of these arboviruses has not been reported in many of these cities. Previous work examined the role of differential Ae. aegypti longevity as a potential explanation for these discrepancies in transmission. To determine factors that were associated with Ae. aegypti longevity in the region, we collected eggs from ovitraps in Tucson, AZ and reared them under multiple experimental conditions in the laboratory to examine the relative impact of temperature and crowding during development, body size, fecundity, and relative humidity during the adult stage. Of the variables studied, we found that the combination of temperature during development, relative humidity, and body size produced the best model to explain variation in age at death. El mosquito Aedes aegypti es el vector primario de los virus de dengue, fiebre amarilla, chikungunya y Zika. Solamente las infecciones con los virus de dengue ocurren en aproximadamente 400 millones de personas cada año. La probabilidad de infección con un virus transmitido por Ae. aegypti es frecuentemente atribuido a la abundancia del mosquito. No obstante, la región del desierto de Arizona-Sonora tiene una abundancia de Ae. aegypti en la mayoría de las áreas urbanas, pero la transmisión local de estos arbovirus no ha sido reportada en muchas de estas ciudades. Trabajos previos han examinado el rol de las diferencias de longevidad en Ae. aegypti como explicación potencial por estas discrepancias en la transmisión. Para determinar que factores fueron asociados con longevidad en Ae. aegypti en la región, colectamos huevos de ovitrampas en Tucson, Arizona y los criamos debajo de múltiples condiciones experimentales en el laboratorio para examinar el impacto relativo de temperatura y competencia para nutrición durante desarrollo, tamaño del cuerpo, capacidad reproductiva, y humedad relativa durante adultez. De las variables estudiados, encontramos que la combinación de temperatura durante desarrollo, humedad relativa, y tamaño del cuerpo produjo el mejor modelo para explicar variación en edad al tiempo de la muerte., (© The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America.)

Vector surveillance is an essential component of vector-borne disease prevention, but many communities lack resources to support extensive surveillance. The Great Arizona Mosquito Hunt (GAMH) was a collaborative citizen science project conducted during 2015-17 to enhance surveillance for Aedes aegypti in Arizona. Citizen science projects engage the public in scientific research in order to further scientific knowledge while improving community understanding of a specific field of science and the scientific process. Participating schools and youth organizations across the state conducted oviposition trapping for 1-4 wk during peak Ae. aegypti season in Arizona and returned the egg sheets to collaborating entomologists for identification. During the 3-year program, 120 different schools and youth organizations participated. Few participants actually collected Aedes eggs in their traps in 2015 or 2017, but about one-third of participants collected eggs during 2016, including 3 areas that were not previously reported to have Ae. aegypti . While relatively few new areas of Ae. aegypti activity were identified, GAMH was found to be a successful method of engaging citizen scientists. Future citizen science mosquito surveillance projects might be useful to further define the ecology and risk for vector-borne diseases in Arizona.

Aedes aegypti (L.; Diptera: Culicidae) has been established in the southwestern United States for several decades, but relationships between humans and mosquitoes in this arid region are not well-characterized. In August 2012, the outdoor premises of 355 houses within 20 neighborhoods in Tucson, Arizona were surveyed for containers that could provide larval habitat for Ae. aegypti mosquitoes. At the same time, a knowledge, attitudes and practices (KAP) questionnaire was administered to a resident of each house surveyed for immature mosquitoes. The KAP questionnaire assessed respondents' knowledge and concerns about vector-borne illnesses as well as practices they used to avoid mosquitoes. Of the houses surveyed, 91% had at least one container present, and 64% had at least one container with standing water. On average, each house had 2.2 containers with water at the time of the survey. The overall House Index (proportion of premises surveyed with at least one container with Ae. aegypti immatures present) was 13%. Based on questionnaire responses, there was a significant positive association between the number of residents in the home and the odds of finding Ae. aegypti positive containers on the premises, while household income showed a significant negative association. The reported frequency of checking for standing water was also significantly associated with the odds of finding immatures, although the nature of this association was ambiguous. Flower pots were the principal type of container with Ae. aegypti larvae. These findings show that larval habitat is widely available even in an arid environment and city with good housing and sanitation infrastructure.

Objectives: We compared the tolerability and efficacy of intranasal subdissociative ketamine to intranasal fentanyl for analgesia of children with acute traumatic pain and investigated the feasibility of a larger noninferiority trial that could investigate the potential opioid-sparing effects of intranasal ketamine., Methods: This randomized controlled trial compared 1 mg/kg intranasal ketamine to 1.5 μg/kg intranasal fentanyl in children 4 to 17 years old with acute pain from suspected isolated extremity fractures presenting to an urban Level II pediatric trauma center from December 2015 to November 2016. Patients, parents, treating physicians, and outcome assessors were blinded to group allocation. The primary outcome, a tolerability measure, was the frequency of cumulative side effects and adverse events within 60 minutes of drug administration. The secondary outcomes included the difference in mean pain score reduction at 20 minutes, the proportion of patients achieving a clinically significant reduction in pain in 20 minutes, total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the emergency department (ED) stay, and the feasibility of enrolling children presenting to the ED in acute pain into a randomized trial conducted under U.S. regulations. All patients were monitored until 6 hours after their last dose of study drug or until admission to the hospital ward or operating room., Results: Of 629 patients screened, 87 received the study drug and 82 had complete data for the primary outcome (41 patients in each group). The median (interquartile range) age was 8 (6-11) years and 62% were male. Baseline pain scores were similar among patients randomized to receive ketamine (73 ± 26) and fentanyl (69 ± 26; mean difference [95% CI] = 4 [-7 to 15]). The cumulative number of side effects was 2.2 times higher in the ketamine group, but there were no serious adverse events and no patients in either group required intervention. The most common side effects of ketamine were bad taste in the mouth (37; 90.2%), dizziness (30; 73.2%), and sleepiness (19; 46.3%). The most common side effects of fentanyl were sleepiness (15; 36.6%), bad taste in the mouth (9; 22%), and itchy nose (9; 22%). No patients experienced respiratory side effects. At 20 minutes, the mean pain scale score reduction was 44 ± 36 for ketamine and 35 ± 29 for fentanyl (mean difference = 9 [95% CI = -4 to 23]). Procedural sedation with ketamine occurred in 28 ketamine patients (65%) and 25 fentanyl patients (57%) prior to completing the study., Conclusions: Intranasal ketamine was associated with more minor side effects than intranasal fentanyl. Pain relief at 20 minutes was similar between groups. Our data support the feasibility of a larger, noninferiority trial to more rigorously evaluate the safety, efficacy, and potential opioid-sparing benefits of intranasal ketamine analgesia for children with acute pain., (© 2017 by the Society for Academic Emergency Medicine.)

Study Design: Retrospective, case-matched review., Objectives: Compare a group of individuals with cerebral palsy (CP) who had intrathecal baclofen (ITB) pumps to a group of individuals with CP who did not have ITB pumps in order to determine if there was a difference in the prevalence of new-onset neuromuscular scoliosis, an increased rate of progression of preexisting neuromuscular scoliosis, or an increased rate of posterior spine fusion surgery in skeletally immature individuals with CP who had ITB pumps., Summary of Background Data: Various authors report conflicting findings, with some reporting an increased incidence or prevalence of scoliosis in individuals with CP who have ITB pumps whereas others report no difference in the rate of scoliosis between groups., Methods: Retrospective chart and radiographic case-matched study in which individuals were matched by gender and Gross Motor Function Classification Scale (GMFCS) level., Results: We found no difference in the rates of new-onset neuromuscular scoliosis for those with CP and ITB pumps and those without ITB pumps. However, we did see a higher rate of progression as well as an increased rate of posterior spine fusion surgery in individuals with CP who had ITB pumps than for those with CP who did not have an ITB pump., Conclusions: We continue to recommend ITB pump therapy for individuals with severe spasticity associated with CP (GMFCS IV and V). There is a significant risk of complications for individuals in general. The risk of neuromuscular scoliosis is relatively high in this population. Our findings suggest that individuals with CP who have ITB pumps and who do or do not have preexisting scoliosis should be monitored closely for either developing new neuromuscular scoliosis or progression of preexisting scoliosis., (Copyright © 2017 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.)

Background: Government-administered adulticiding is frequently conducted in response to dengue transmission worldwide. Anecdotal evidence suggests that spraying may create a "false sense of security" for residents. Our objective was to determine if there was an association between residents' reporting outdoor spatial insecticide spraying as way to prevent dengue transmission and both their reported frequency of dengue prevention practices and household entomological indices in Hermosillo, Mexico., Methodology/principal Findings: A non-probabilistic survey of 400 households was conducted in August 2014. An oral questionnaire was administered to an adult resident and the outer premises of the home were inspected for water-holding containers and presence of Ae. aegypti larvae and pupae. Self-reported frequency of prevention practices were assessed among residents who reported outdoor spatial spraying as a strategy to prevent dengue (n = 93) and those who did not (n = 307). Mixed effects negative binomial regression was used to assess associations between resident's reporting spraying as a means to prevent dengue and container indices. Mixed effects logistic regression was used to determine associations with presence/absence of larvae and pupae. Those reporting spatial spraying disposed of trash less frequently and spent less time indoors to avoid mosquitoes. They also used insecticides and larvicides more often and covered their water containers more frequently. Their backyards had more containers positive for Ae. aegypti (RR = 1.92) and there was a higher probability of finding one or more Ae. aegypti pupae (OR = 2.20). Survey respondents that reported spatial spraying prevented dengue were more likely to be older and were exposed to fewer media sources regarding prevention., Conclusions/significance: The results suggest that the perception that outdoor spatial spraying prevents dengue is associated with lower adoption of prevention practices and higher entomological risk. This provides some support to the hypothesis that spraying may lead to a "false sense of security". Further investigations to clarify this relationship should be conducted. Government campaigns should emphasize the difficulty in controlling Ae. aegypti mosquitoes and the need for both government and community action to minimize risk of dengue transmission.

Dengue virus, primarily transmitted by the Aedes aegypti (L.) mosquito, has rapidly expanded in geographic extent over the past several decades. In some areas, however, dengue fever has not emerged despite established Ae. aegypti populations. The reasons for this are unclear and have sometimes been attributed to socio-economic differences. In 2013 we compared Ae. aegypti adult density and population age structure between two cities in Sonora, Mexico: Hermosillo, which has regular seasonal dengue virus transmission, and Nogales, which has minimal transmission. Larval and pupal abundance was greater in Nogales, and adult density was only higher in Hermosillo during September. Population age structure, however, was consistently older in Hermosillo. This difference in longevity may have been one factor that limited dengue virus transmission in Nogales in 2013, as a smaller proportion of Ae. aegypti females survived past the extrinsic incubation period., (© The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Golgi-localized γ-ear-containing ARF binding protein 3 (GGA3) is a monomeric clathrin adaptor that has been shown to regulate the trafficking of the Beta-site APP-cleaving enzyme (BACE1), which is required for production of the Alzheimer's disease (AD)-associated amyloid βpeptide. Our previous studies have shown that BACE1 is degraded via the lysosomal pathway and that depletion of GGA3 results in increased BACE1 levels and activity owing to impaired lysosomal trafficking and degradation. We further demonstrated the role of GGA3 in the regulation of BACE1 in vivo by showing that BACE1 levels are increased in the brain of GGA3 null mice. We report here that GGA3 deletion results in novelty-induced hyperactivity and decreased anxiety-like behaviors. Given the pivotal role of GABAergic transmission in the regulation of anxiety-like behaviors, we performed electrophysiological recordings in hippocampal slices and found increased phasic and decreased tonic inhibition in the dentate gyrus granule cells (DGGC). Moreover, we found that the number of inhibitory synapses is increased in the dentate gyrus of GGA3 null mice in further support of the electrophysiological data. Thus, the increased GABAergic transmission is a leading candidate mechanism underlying the reduced anxiety-like behaviors observed in GGA3 null mice. All together these findings suggest that GGA3 plays a key role in GABAergic transmission. Since BACE1 levels are elevated in the brain of GGA3 null mice, it is possible that at least some of these phenotypes are a consequence of increased processing of BACE1 substrates.

Mosquito-borne illnesses like West Nile virus (WNV) and dengue are growing threats to the United States. Proactive mosquito control is one strategy to reduce the risk of disease transmission. In 2012, we measured the public's willingness to pay (WTP) for increased mosquito control in two cities: Key West, FL, where there have been recent dengue outbreaks, and Tucson, AZ, where dengue vectors are established and WNV has been circulating for over a decade. Nearly three quarters of respondents in both cities (74% in Tucson and 73% in Key West) would be willing to pay $25 or more annually toward an increase in publicly funded mosquito control efforts. WTP was positively associated with income (both cities), education (Key West), and perceived mosquito abundance (Tucson). Concerns about environmental impacts of mosquito control were associated with lower WTP in Key West. Expanded mosquito control efforts should incorporate public opinion as they respond to evolving disease risks., (© The American Society of Tropical Medicine and Hygiene.)

Background Context: Although total hip arthroplasty (THA) and total knee arthroplasty (TKA) have been widely accepted as highly cost-effective procedures, spine surgery for the treatment of degenerative conditions does not share the same perception among stakeholders. In particular, the sustainability of the outcome and cost-effectiveness following lumbar spinal stenosis (LSS) surgery compared with THA/TKA remain uncertain., Purpose: The purpose of the study was to estimate the lifetime incremental cost-utility ratios for decompression and decompression with fusion for focal LSS versus THA and TKA for osteoarthritis (OA) from the perspective of the provincial health insurance system (predominantly from the hospital perspective) based on long-term health status data at a median of 5 years after surgical intervention., Study Design/setting: An incremental cost-utility analysis from a hospital perspective was based on a single-center, retrospective longitudinal matched cohort study of prospectively collected outcomes and retrospectively collected costs., Patient Sample: Patients who had undergone primary one- to two-level spinal decompression with or without fusion for focal LSS were compared with a matched cohort of patients who had undergone elective THA or TKA for primary OA., Outcome Measures: Outcome measures included incremental cost-utility ratio (ICUR) ($/quality adjusted life year [QALY]) determined using perioperative costs (direct and indirect) and Short Form-6D (SF-6D) utility scores converted from the SF-36., Methods: Patient outcomes were collected using the SF-36 survey preoperatively and annually for a minimum of 5 years. Utility was modeled over the lifetime and QALYs were determined using the median 5-year health status data. The primary outcome measure, cost per QALY gained, was calculated by estimating the mean incremental lifetime costs and QALYs for each diagnosis group after discounting costs and QALYs at 3%. Sensitivity analyses adjusting for +25% primary and revision surgery cost, +25% revision rate, upper and lower confidence interval utility score, variable inpatient rehabilitation rate for THA/TKA, and discounting at 5% were conducted to determine factors affecting the value of each type of surgery., Results: At a median of 5 years (4-7 years), follow-up and revision surgery data was attained for 85%-FLSS, 80%-THA, and 75%-THA of the cohorts. The 5-year ICURs were $21,702/QALY for THA; $28,595/QALY for TKA; $12,271/QALY for spinal decompression; and $35,897/QALY for spinal decompression with fusion. The estimated lifetime ICURs using the median 5-year follow-up data were $5,682/QALY for THA; $6,489/QALY for TKA; $2,994/QALY for spinal decompression; and $10,806/QALY for spinal decompression with fusion. The overall spine (decompression alone and decompression and fusion) ICUR was $5,617/QALY. The estimated best- and worst-case lifetime ICURs varied from $1,126/QALY for the best-case (spinal decompression) to $39,323/QALY for the worst case (spinal decompression with fusion)., Conclusion: Surgical management of primary OA of the spine, hip, and knee results in durable cost-utility ratios that are well below accepted thresholds for cost-effectiveness. Despite a significantly higher revision rate, the overall surgical management of FLSS for those who have failed medical management results in similar median 5-year and lifetime cost-utility compared with those of THA and TKA for the treatment of OA from the limited perspective of a public health insurance system., (Copyright © 2014 Elsevier Inc. All rights reserved.)

McArdle disease is caused by a deficiency of myophosphorylase and currently a satisfactory treatment is not available. The injection of notexin into, or the layering of notexin onto, the muscles of affected sheep resulted in necrosis followed by regeneration of muscle fibres with the expression of both non-muscle isoforms of phosphorylase within the fibres and a reduction of the amount of glycogen in the muscle with an increase in the strength of contraction and a decrease in fatiguability in the muscle fibres. The sustained re-expression of both the brain and liver isoforms of phosphorylase within the muscle fibres provides further emphasis that strategies to enhance the re-expression of these isoforms should be investigated as a possible treatment for McArdle disease., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Traumatic brain injury (TBI) results in significant disability due to cognitive deficits particularly in attention, learning and memory, and higher-order executive functions. The role of TBI in chronic neurodegeneration and the development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and most recently chronic traumatic encephalopathy (CTE) is of particular importance. However, despite significant effort very few therapeutic options exist to prevent or reverse cognitive impairment following TBI. In this review, we present experimental evidence of the known secondary injury mechanisms which contribute to neuronal cell loss, axonal injury, and synaptic dysfunction and hence cognitive impairment both acutely and chronically following TBI. In particular we focus on the mechanisms linking TBI to the development of two forms of dementia: AD and CTE. We provide evidence of potential molecular mechanisms involved in modulating Aβ and Tau following TBI and provide evidence of the role of these mechanisms in AD pathology. Additionally we propose a mechanism by which Aβ generated as a direct result of TBI is capable of exacerbating secondary injury mechanisms thereby establishing a neurotoxic cascade that leads to chronic neurodegeneration.

Traumatic brain injury (TBI) is one of the most robust environmental risk factors for Alzheimer's disease (AD). Compelling evidence is accumulating that a single event of TBI is associated with increased levels of Aβ. However, the underlying molecular mechanisms remain unknown. We report here that the BACE1 interacting protein, GGA3, is depleted while BACE1 levels increase in the acute phase after injury (48 h) in a mouse model of TBI. We further demonstrated the role of GGA3 in the regulation of BACE1 in vivo by showing that BACE1 levels are increased in the brain of GGA3-null mice. We next found that head trauma potentiates BACE1 elevation in GGA3-null mice in the acute phase after TBI, and discovered that GGA1, a GGA3 homolog, is a novel caspase-3 substrate depleted at 48 h after TBI. Moreover, GGA1 silencing potentiates BACE1 elevation induced by GGA3 deletion in neurons in vitro, indicating that GGA1 and GGA3 synergistically regulate BACE1. Accordingly, we found that levels of both GGA1 and GGA3 are depleted while BACE1 levels are increased in a series of postmortem AD brains. Finally, we show that GGA3 haploinsufficiency results in sustained elevation of BACE1 and Aβ levels while GGA1 levels are restored in the subacute phase (7 d) after injury. In conclusion, our data indicate that depletion of GGA1 and GGA3 engender a rapid and robust elevation of BACE1 in the acute phase after injury. However, the efficient disposal of the acutely accumulated BACE1 solely depends on GGA3 levels in the subacute phase of injury.

Aedes aegypti, the primary vector of dengue virus, is well established throughout urban areas of the Southwestern US, including Tucson, AZ. Local transmission of the dengue virus, however, has not been reported in this area. Although many factors influence the distribution of the dengue virus, we hypothesize that one contributing factor is that the lifespan of female Ae. aegypti mosquitoes in the Southwestern US is too short for the virus to complete development and be transmitted to a new host. To test this we utilized two age grading techniques. First, we determined parity by analyzing ovarian tracheation and found that only 40% of Ae. aegypti females collected in Tucson, AZ were parous. The second technique determined transcript levels of an age-associated gene, Sarcoplasmic calcium-binding protein 1 (SCP-1). SCP-1 expression decreased in a predictable manner as the age of mosquitoes increased regardless of rearing conditions and reproductive status. We developed statistical models based on parity and SCP-1 expression to determine the age of individual, field collected mosquitoes within three age brackets: nonvectors (0-5 days post-emergence), unlikely vectors (6-14 days post-emergence), and potential vectors (15+ days post-emergence). The statistical models allowed us to accurately group individual wild mosquitoes into the three age brackets with high confidence. SCP-1 expression levels of individual, field collected mosquitoes were analyzed in conjunction with parity status. Based on SCP-1 transcript levels and parity data, 9% of collected mosquitoes survived more than 15 days post emergence.

Aedes aegypti has reappeared in urban communities in the southwestern U.S.A. in the 1990s after a 40-year absence. In 2003 and 2004, a systematic survey was conducted throughout metropolitan Tucson, AZ, to identify human and environmental factors associated with Ae. aegypti distribution within an arid urban area. Aedes aegypti presence and abundance were measured monthly using the Centers for Disease Control and Prevention enhanced oviposition traps at sampling sites established in a grid at 3- to 4-km intervals across the city. Sampling occurred in the summer rainy season (July through September), the peak of mosquito activity in the region. Multiple regression analyses were conducted to determine relationships between mosquito density and factors that could influence mosquito distribution. House age was the only factor that showed a consistent significant association with Ae. aegypti abundance in both years: older houses had more mosquito eggs. This is the 1st study of Ae. aegypti distribution at a local level to identify house age as an explanatory factor independent of other human demographic factors. Further research into the reasons why mosquitoes were more abundant around older homes may help inform and refine future vector surveillance and control efforts in the event of a dengue outbreak in the region.

Relatively little is known about regulatory T (Treg) cells and their functional responses in dogs. We have used the cross-reactive anti-mouse/rat Foxp3 antibody clone FJK-16s to identify a population of canine CD4(+) FOXP3(high) T cells in both the peripheral blood (PB) and popliteal lymph node (LN). FOXP3(+) cells in both PB and LN yielded positive staining with the newly developed anti-murine/human Helios antibody clone 22F6, consistent with the notion that they were naturally occurring Treg cells. Stimulation of mononuclear cells of LN origin with concanavalin A (Con A) in vitro yielded increased proportions and median fluorescence intensity of FOXP3 expression by both CD4(+) and CD8(+) T cells. Removal of the Con A and continued culture disclosed a CD4(+)  FOXP3(high) population, distinct from the CD4(+) FOXP3(intermediate) T cells; very few CD8(+) FOXP3(high) T cells were observed, though CD8(+) FOXP3(intermediate) cells were present in equal abundance to CD4(+) FOXP3(intermediate) cells. The CD4(+)  FOXP3(high) T cells were thought to represent activated Treg cells, in contrast to the FOXP3(intermediate) cells, which were thought to be a more heterogeneous population comprising predominantly activated conventional T cells. Co-staining with interferon-γ (IFN-γ) supported this notion, because the FOXP3(high) T cells were almost exclusively IFN-γ(-) , whereas the FOXP3(intermediate) cells expressed a more heterogeneous IFN-γ phenotype. Following activation of mononuclear cells with Con A and interleukin-2, the 5% of CD4(+) T cells showing the highest CD25 expression (CD4(+) CD25(high) ) were enriched in cells expressing FOXP3. These cells were anergic in vitro, in contrast to the 20% of CD4(+) T cells with the lowest CD25 expression (CD4(+) CD25(-) ), which proliferated readily. The CD4(+) CD25(high) FOXP3(high) T cells were able to suppress the proliferation of responder CD4(+) T cells in vitro, in contrast to the CD4(+) CD25(-) cells, which showed no regulatory properties.

BACE1 (beta-site amyloid precursor protein-cleaving enzyme 1) is a membrane-tethered member of the aspartyl proteases, essential for the production of beta-amyloid, a toxic peptide that accumulates in the brain of subjects affected by Alzheimer disease. The BACE1 C-terminal fragment contains a DXXLL motif that has been shown to bind the VHS (VPS27, Hrs, and STAM) domain of GGA1-3 (Golgi-localized gamma-ear-containing ARF-binding proteins). GGAs are trafficking molecules involved in the transport of proteins containing the DXXLL signal from the Golgi complex to endosomes. Moreover, GGAs bind ubiquitin and traffic synthetic and endosomal ubiquitinated cargoes to lysosomes. We have previously shown that depletion of GGA3 results in increased BACE1 levels and activity because of impaired lysosomal degradation. Here, we report that the accumulation of BACE1 is rescued by the ectopic expression of GGA3 in H4 neuroglioma cells depleted of GGA3. Accordingly, the overexpression of GGA3 reduces the levels of BACE1 and beta-amyloid. We then established that mutations in the GGA3 VPS27, Hrs, and STAM domain (N91A) or in BACE1 di-leucine motif (L499A/L500A), able to abrogate their binding, did not affect the ability of ectopically expressed GGA3 to rescue BACE1 accumulation in cells depleted of GGA3. Instead, we found that BACE1 is ubiquitinated at lysine 501 and is mainly monoubiquitinated and Lys-63-linked polyubiquitinated. Finally, a GGA3 mutant with reduced ability to bind ubiquitin (GGA3L276A) was unable to regulate BACE1 levels both in rescue and overexpression experiments. These findings indicate that levels of GGA3 tightly and inversely regulate BACE1 levels via interaction with ubiquitin sorting machinery.

Background: Ethanol neurobehavioural teratogenicity is a leading cause of developmental mental deficiency, in which the hippocampus is a target site of injury. The multi-faceted mechanism of ethanol teratogenicity is not completely understood. This study tested the hypothesis that chronic ethanol exposure (CEE), via chronic maternal ethanol administration, increases cytochrome P450 2E1 (CYP2E1) expression and alters hypothalamic-pituitary-adrenal (HPA) axis activity in the maternal-fetal unit during the third-trimester-equivalent of gestation., Methods: Pregnant Dunkin-Hartley-strain guinea pigs received daily oral administration of ethanol (4 g ethanol/kg maternal body weight) or isocaloric-sucrose/pair-feeding (control) throughout gestation (term, about gestational day (GD) 68). On GD 45, 55 and 65, pregnant animals were euthanized 2h after the last daily dose. Maternal and fetal body weights and fetal hippocampal brain weight were determined. Maternal and fetal samples were collected for the determination of liver CYP2E1 enzymatic activity and plasma free cortisol and ACTH concentrations., Results: CEE, with maternal blood ethanol concentration of 108-124 mg/dl at 2h after the last dose, decreased fetal hippocampal weight only at GD 65 and had no effect on fetal body weight compared with control. CYP2E1 activity increased with gestational age in the fetal liver microsomal and mitochondrial fractions. CEE increased CYP2E1 activity in the microsomal and mitochondrial fractions of maternal liver at the three gestational ages and in both hepatic subcellular fractions of the GD 65 fetus compared with control. There was a gestational-age-dependent increase in maternal and fetal plasma free cortisol concentrations, but no effect of CEE compared with control. Maternal and fetal plasma ACTH concentrations were unaffected by CEE compared with control, and were virtually unchanged during the third-trimester-equivalent that was studied., Conclusion: These data demonstrate that, in the pregnant guinea pig, this CEE regimen increases liver CYP2E1 activity, without affecting HPA axis function, in the maternal-fetal unit during near-term gestation. The CEE-induced increase in liver CYP2E1 activity and potential oxidative stress in the maternal-fetal unit may play a role in the pathogenesis of ethanol teratogenicity., (Copyright (c) 2009 Elsevier Inc. All rights reserved.)

As with many skeletal muscle diseases, the extraocular muscles (EOMs) are spared in skeletal muscle alpha-actin diseases, with no ophthalmoplegia even in severely affected patients. We hypothesised that the extraocular muscles sparing in these patients was due to significant expression of cardiac alpha-actin, the alpha-actin isoform expressed in heart and foetal skeletal muscle. We have shown by immunochemistry, Western blotting and a novel MRM-mass spectrometry technique, comparable levels of cardiac alpha-actin in the extraocular muscles of human, pig and sheep to those in the heart. The sparing of extraocular muscles in skeletal muscle alpha-actin disease is thus probably due to greater levels of cardiac alpha-actin, than the negligible amounts in skeletal muscles, diluting out the effects of the mutant skeletal muscle alpha-actin.

At present there is no satisfactory treatment for McArdle's disease, deficiency of myophosphorylase. Injection of modified adenovirus 5 (AdV5) and adeno-associated virus 2 (AAV2) vectors containing myophosphorylase expression cassettes, into semitendinosus muscle of sheep with McArdle's disease, produced expression of functional myophosphorylase and some re-expression of the non-muscle glycogen phosphorylase isoforms (both liver and brain) in regenerating fibres. Expression of both non-muscle isoforms was also seen after control injections of AdV5LacZ vectors. There was up to an order of magnitude greater expression of phosphorylase after myophosphorylase vector injection than after LacZ controls (62% of sections with over 1000 positive muscle fibres, versus 7%). The results presented here suggest that the use of viral vector-mediated phosphorylase gene transfer may be applicable to the treatment of McArdle's disease and that sustained re-expression of the brain and liver isoforms should also be investigated as a possible treatment.

We report three heterozygous missense mutations of the skeletal muscle alpha actin gene (ACTA1) in three unrelated cases of congenital fiber type disproportion (CFTD) from Japan and Australia. This represents the first genetic cause of CFTD to be identified and confirms that CFTD is genetically heterogeneous. The three mutations we have identified Leucine221Proline, Aspartate292Valine, and Proline332Serine are novel. They have not been found previously in any cases of nemaline, actin, intranuclear rod, or rod-core myopathy caused by mutations in ACTA1. It remains unclear why these mutations cause type 1 fiber hypotrophy but no nemaline bodies. The three mutations all lie on one face of the actin monomer on the surface swept by tropomyosin during muscle activity, which may suggest a common pathological mechanism. All three CFTD cases with ACTA1 mutations had severe congenital weakness and respiratory failure without ophthalmoplegia. There were no clinical features specific to CFTD cases with ACTA1 mutations, but the presence of normal eye movements in a severe CFTD patient may be an important clue for the presence of a mutation in ACTA1.

The Stockholm Convention on Persistent Organic Pollutants provides a framework for international action on 12 persistent, bioaccumulative and toxic chemicals of global concern. While production and use of most of the listed chemicals will shortly be eliminated, there is widespread agreement that DDT will continue to be needed for disease vector control. Science played a key role in informing policy makers from developed and developing countries who drafted the DDT provision of the convention. This paper examines both the science and the politics that contributed to an international consensus on DDT.

Mutations within the human skeletal muscle alpha-actin gene cause three different skeletal muscle diseases. Functional studies of the mutant proteins are necessary to better understand the pathogenesis of these diseases, however, no satisfactory system for the expression of mutant muscle actin proteins has been available. We investigated the baculovirus expression vector system (BEVS) for the abundant production of both normal and mutant skeletal muscle alpha-actin. We show that non-mutated actin produced in the BEVS behaves similarly to native actin, as shown by DNase I affinity purification, Western blotting, and consecutive cycles of polymerisation and depolymerisation. Additionally, we demonstrate the production of mutant actin proteins in the BEVS, without detriment to the insect cells in which they are expressed. The BEVS therefore is the method of choice for studying mutant actin proteins causing human diseases.

Two species of leafrollers, Argyrotaenia citrana (Fernald) and Pandemis pyrusana Kearfott, represent serious obstacles to the implementation of mating disruption for control of codling moth in coastal California apple orchards. Larval and adult densities of A. citrana and P. pyrusana and subsequent fruit damage were compared under different codling moth control treatments. Leafroller larval counts and levels of fruit damage were significantly higher in most plots that were untreated or treated only with codling moth pheromone. Leafroller fruit damage levels in these plots were commonly between 10 and 15% at harvest. As summer larval counts were good predictors of fruit damage levels, larval sampling could be a useful tool for predicting leafroller outbreaks. Use of pheromone trapping for A. citrana to detect localized outbreaks within an orchard was not useful and failed to correlate with larval numbers, whereas adult monitoring for P. pyrusana appears more promising. Efforts to implement a codling moth mating-disruption program in California must include changes in strategies for monitoring and controlling leafroller species.

Between 1988 and 1996, 16 patients who underwent a total of 18 slotted acetabular augmentation procedures were managed postoperatively without a spica cast, by using instead a protocol of limited weight bearing and restriction of hip range of motion. Postoperatively, no patients experienced hip stiffness. No patients exhibited any migration or change of position of their bone graft. Radiographic examination revealed the following: center-edge angle (CEA) averaged 3 degrees preoperatively and 54 degrees postoperatively. Acetabular index averaged 35 degrees preoperatively and 18 degrees postoperatively. No patients experienced any deleterious effects by not using a spica cast. We believe that by obviating the spica cast, we may ease the postoperative recovery for patients, avoid postoperative hip stiffness, and thereby expand the applications of this safe and reliable method of acetabular reconstruction in selected patients.

Twenty-seven patients with rheumatoid arthritis underwent cementless total hip arthroplasty from 1982 through 1989. We performed all operations through a posterior approach. Postoperatively, patient convalescence consisted of ambulation with crutches, followed by weight bearing as tolerated until pain and discomfort subsided. We contacted 25 (92.5%) patients for follow-up. Combined, these patients received 34 total hip arthroplasties. The patients ranged in age from 14 to 69 years old with a mean age of 42.9 years. The follow-up period ranged from two to eight years with a mean of five and one-half years. The mean preoperative total Harris hip score was 48 (range 31-68). The mean total Harris hip score at latest follow-up was 80 (range 44-95). Hip pain status and functional ability were important indicators of treatment efficacy. The lower incidence of pain, as well as the increase in functional abilities experienced by the patients, suggests that cementless total hip arthroplasty is a preferable alternative to fixed arthroplasty in patients with rheumatoid arthritis.

The quantitative role of atrial natriuretic factor (ANF) in mediating the natriuresis induced by acute volume loading was determined in these studies. Plasma level of ANF (PANF), glomerular filtration rate (GFR), and renal excretory responses were measured in three groups of anesthetized Sprague-Dawley rats. In one group of rats (n = 8), acute volume expansion was established by intravenous infusion of saline (5% body wt) over a period of 30 min. A second group of rats (n = 13) was infused with synthetic ANF (2 micrograms X kg-1 X h-1 iv) to mimic the high PANF observed during acute volume loading. A third group (n = 13) served as control. PANF was similar and significantly elevated (P less than 0.05) in volume-expanded and ANF-infused groups compared with control. In control rats, PANF measured 122.0 +/- 12.1 pg/ml, whereas it averaged 389.4 +/- 30.3 pg/ml for volume-expanded and 368.1 +/- 22.3 pg/ml for ANF-infused rats. GFR was also comparable and significantly increased (P less than 0.05) in volume-expanded and ANF-infused groups compared with control rats. Infusion of ANF at a dose to mimic PANF obtained during acute volume expansion resulted in a fourfold increase in the fractional excretion of sodium. The results of these studies suggest that ANF may play an important quantitative role in promoting natriuresis during acute volume expansion.

A series of novel benzo- and pyrido-1,4-oxazepinones and -thiones which represents a new structural class of compounds possessing H1 antihistaminic activity was synthesized, and the SARs were evaluated. The antihistaminic activity was determined by blockade of histamine-induced lethality in guinea pigs. The sedative potential was determined by comparison of the EEG profiles of the compounds with those of known sedating and nonsedating antihistamines. Several of the compounds were shown to possess potent H1 antihistaminic activity and to be free of the cortical slowing with synchronized waves and spindling activity found in the EEG of sedative antihistamines. One compound, 2-[2-(dimethylamino)ethyl]-3,4-dihydro-4-methylpyrido[3,2-f]-1,4- oxazepine-5(2H)-thione (rocastine) is currently undergoing clinical evaluation as a nonsedating H1 antihistamine.