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The long-horned tick, Haemaphysalis longicornis Neumann (Ixodida: Ixodidae) was recently introduced to the United States from its native range in Asia. Although H. longicornis transmits numerous disease-causing pathogens in its native range, it is unclear to what extent H. longicornis will act as a disease vector in the United States. The ability of H. longicornis to acquire pathogens likely depends on overlap with resident tick species in both habitat and pathogens transmitted within its introduced range. To assess the potential overlap in habitat and pathogens between invasive H. longicornis and resident tick species, we field-collected ticks across southeastern Pennsylvania and tested them for pathogens. We then contextualized the risk of pathogen transmission to and by H. longicornis at sites where it overlaps with the current vector species using a network of vectored pathogens. None of the collected H. longicornis individuals tested positive for any pathogens. However, we found significant overlap in habitat use among H. longicornis and resident tick nymphs, as well as several overlaps in the pathogens vectored by resident ticks and those carried by H. longicornis in Asia. These findings indicate a high but yet-to-be-realized potential for H. longicornis to acquire North American tick-borne pathogens., (© The Author(s) 2025. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Altered fetal growth, which can occur due to environmental stressors during pregnancy, may program a susceptibility to metabolic disease. Gestational exposure to the air pollutant ozone is associated with fetal growth restriction in humans and rodents. However, the impact of this early life ozone exposure on offspring metabolic risk has not yet been investigated. In this study, fetal growth restriction was induced by maternal inhalation of 0.8 ppm ozone on gestation days 5 and 6 (4 hr/day) in Long Evans rats. To uncover any metabolic inflexibility, or an impaired ability to respond to a high-fat diet (HFD), a subset of peri-adolescent male and female offspring from filtered air or ozone exposed dams were fed HFD (45% kcal from fat) for 3 days. By 6 weeks of age, male and female offspring from ozone-exposed dams were heavier than offspring from air controls. Furthermore, offspring from ozone-exposed dams had greater daily caloric consumption and reduced metabolic rate when fed HFD. In addition to energy imbalance, HFD-fed male offspring from ozone-exposed dams had dyslipidemia and increased adiposity, which was not evident in females. HFD consumption in males resulted in the activation of the protective 5'AMP-activated protein kinase (AMPKα) and sirtuin 1 (SIRT1) pathways in the liver, regardless of maternal exposure. Unlike males, ozone-exposed female offspring failed to activate these pathways, retaining hepatic triglycerides following HFD consumption that resulted in increased inflammatory gene expression and reduced insulin signaling genes. Taken together, maternal ozone exposure in early pregnancy programs impaired metabolic flexibility in offspring, which may increase susceptibility to obesity in males and hepatic dysfunction in females., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA.)

Large, heavy breasts are a common complaint among women causing various functional and aesthetic concerns. The plastic surgery community has offered a variety of surgical techniques to address this condition. Most of these operations developed during the 1970s-1980s cemented their place in history as fundamentals of breast reduction surgery and are still widely taught today. Despite ongoing plastic surgery advances, long-term complications surrounding breast reduction surgery remain a concern, even to experienced surgeons. Its apparent trends have shifted focus over time; from the basics of developing a patient-safe and easily replicable technique, toward developing more refined maneuvers allowing surgeons to reach desired and long-lasting outcomes while preventing known complications. The bottoming out phenomena, lack of nipple areola complex sensitivity, upper pole emptiness with low setting breasts and high revision rates still plague the breast reduction landscape. We present a novel technique involving a pectoralis major-based myo-glandular flap with breast parenchymal suspension to the upper chest wall to combat bottoming out and upper pole emptiness. These procedural elements allow the breasts to attain not only acceptable results, with smaller, round and well-projected breasts, but also to create an active opposing vector to resist the gravitational forces which otherwise pull breast tissue inferiorly creating the bottoming out deformity.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

A critical part of community based human health risk assessment following chemical exposure is identifying sources of susceptibility. Life stage is one such susceptibility. A prototypic air pollutant, ozone (O 3 ) induces dysfunction of the pulmonary, cardiac, and nervous systems. Long-term exposure may cause oxidative stress (OS). The current study explored age-related and subchronic O 3 -induced changes in OS in brain regions of rats. To build a comprehensive assessment of OS-related effects of O 3 , a tripartite approach was implemented focusing on 1) the production of reactive oxygen species (ROS) [NADPH Quinone oxidoreductase 1, NADH Ubiquinone reductase] 2) antioxidant homeostasis [total antioxidant substances, superoxide dismutase, γ-glutamylcysteine synthetase] and 3) an assessment of oxidative damage [total aconitase and protein carbonyls]. Additionally, a neurobehavioral evaluation of motor activity was compared to these OS measures. Male Brown Norway rats (4, 12, and 24 months of age) were exposed to air or O 3 (0.25 or 1 ppm) via inhalation for 6 h/day, 2 days per week for 13 weeks. A significant decrease in horizontal motor activity was noted only in 4-month old rats. Results on OS measures in frontal cortex (FC), cerebellum (CB), striatum (STR), and hippocampus (HIP) indicated life stage-related increases in ROS production, small decreases in antioxidant homeostatic mechanisms, a decrease in aconitase activity, and an increase in protein carbonyls. The effects of O 3 exposure were brain area-specific, with the STR being more sensitive. Regarding life stage, the effects of O 3 were greater in 4-month-old rats, which correlated with horizontal motor activity. These results indicate that OS may be increased in specific brain regions after subchronic O 3 exposure, but the interactions between age and exposure along with their consequences on the brain require further investigation., (Published by Elsevier Inc.)

The influence of maternal high-fat diet (HFD) on metabolic response to ozone was examined in Long-Evans rat offspring. F0 females were fed control diet (CD; 10%kcal from fat) or HFD (60%kcal from fat) starting at post-natal day (PND) 30. Rats were bred on PND 72. Dietary regimen was maintained until PND 30 when all offspring were switched to CD. On PND 40, F1 offspring (n = 10/group/sex) were exposed to air or 0.8 ppm ozone for 5 h. Serum samples were collected for global metabolomic analysis (n = 8/group/sex). Offspring from HFD dams had increased body fat and weight relative to CD. Metabolomic analysis revealed significant sex-, diet-, and exposure-related changes. Maternal HFD increased free fatty acids and decreased phospholipids (male > female) in air-exposed rats. Microbiome-associated histidine and tyrosine metabolites were increased in both sexes, while 1,5-anhydroglucitol levels decreased in males indicating susceptibility to insulin resistance. Ozone decreased monohydroxy fatty acids and acyl carnitines and increased pyruvate along with TCA cycle intermediates in females (HFD > CD). Ozone increased various amino acids, polyamines, and metabolites of gut microbiota in HFD female offspring indicating gut microbiome alterations. Collectively, these data suggest that maternal HFD increases offspring susceptibility to metabolic alterations in a sex-specific manner when challenged with environmental stressors.

There is growing interest in understanding how maternal diet might affect the sensitivity of offspring to environmental exposures. Previous studies demonstrated that adult rat offspring (approximately 6-months-old) from dams given a high-fat diet (HFD) prior to, during, and after pregnancy displayed elevated pulmonary responses to an acute ozone (O 3 ) exposure. The aim of this study was to examine the influence of maternal and perinatal HFD on pulmonary and metabolic responses to O 3 in male and female young-adult offspring (approximately 3-month old). One-month-old F0 female Long-Evans rats commenced HFD (60% kcal from fat) or control diet (CD; 10.5% kcal from fat) and were bred on PND 72. Offspring were maintained on respective HFD or CD until PND 29 when all groups were switched to CD. The 3-months-old female and male offspring (n = 10/group) were exposed to air or 0.8 ppm O 3 for 5hr/day for 2 consecutive days. Maternal and perinatal HFD significantly increased body weight and body fat % in offspring regardless of gender. Ozone exposure, but not maternal and perinatal diet, induced hyperglycemia and glucose intolerance in the offspring. Ozone-induced alterations in pulmonary function were exacerbated by maternal and perinatal HFD in both offspring genders. Pulmonary injury/inflammation markers in response to O 3 exposure such as bronchoalveolar lavage fluid total protein, lactate dehydrogenase, total cells, and neutrophils were further augmented in offspring (males>females) from dams fed the HFD. Data suggest that maternal and perinatal HFD may enhance the susceptibility of offspring to O 3 -induced pulmonary injury and that these effects may be sex-specific.

We describe a case of complex, posttraumatic skull and orbital deformities that were evaluated and treated with advanced computer technology, including virtual surgical planning, three-dimensional (3D) modeling, and printed patient custom implants (PCI) fabricated by 3D printing. A 50-year-old man presented to our craniofacial referral center 1 year after failed reduction of complex left orbital, zygomatic, and frontal bone fractures due to a motorcycle collision. The patient's chief complaint was debilitating diplopia in all fields of gaze. On examination, he had left enophthalmos, left canthal displacement, lower eyelid ectropion, vertical orbital dystopia, and a laterally and inferiorly displaced, comminuted zygoma with orbital rim and frontal bone defects. The normal orbit was mirrored to precisely guide repositioning of the globe, orbital reconstruction, and cranioplasty. Preinjury appearance with normal globe position was restored with complete resolution of diplopia. Modern 3D technology allows the surgeon to better analyze complex orbital deformities and precisely plan surgical correction with the option of printing a PCI. These techniques were successfully applied to resolve a case of debilitating diplopia and aesthetic deficits after facial trauma. Further application of advanced 3D computer technology can potentially improve the results of severe orbital and craniofacial trauma reconstruction.

Human and animal studies indicate that maternal obesity can negatively impact aspects of metabolism and neurodevelopment in the offspring. Not known, however, is whether maternal exercise can alter these adverse outcomes. In this study, Long-Evans female rats were provided a high fat (60%; HFD) or control diet (CD) 44days before mating and throughout gestation and lactation. Running wheels were available to half of each diet group during the gestational period only, resulting in four conditions: CD diet with (CDRW) or without (sedentary; CDSED) exercise, and HFD with (HFRW) or without (HFSED) exercise. Only male offspring (one per litter) were available for this study: they were put on control diet two weeks after weaning and examined using behavioral evaluations up to four months of age. Before weaning, offspring of CDRW dams weighed less than offspring from CDSED or HFD dams. After weaning, the lower weight in CDRW offspring generally persisted. Adult offspring from HFSED dams performed worse than the HFRW group in a Morris water maze during initial spatial training as well as reversal learning; memory was not impacted. No differences between groups were seen in tests of novel object recognition, social approach, or chocolate milk preference. Thus, maternal diet and exercise produced differential effects on body weights and cognitive behaviors in the offspring, and the data demonstrate a positive impact of maternal exercise on the offspring in that it ameliorated some deleterious behavioral effects of a maternal high fat diet., (Published by Elsevier Inc.)

Epidemiological and experimental data suggest that obesity exacerbates the health effects of air pollutants such as ozone (O 3 ). Maternal inactivity and calorically rich diets lead to offspring that show signs of obesity. Exacerbated O 3 susceptibility of offspring could thus be manifested by maternal obesity. Thirty-day-old female Long-Evans rats were fed a control (CD) or high-fat (HF) (60% calories) diet for 6 wks and then bred. GD1 rats were then housed with a running wheel (RW) or without a wheel (SED) until parturition, creating four groups of offspring: CD-SED, CD-RW, HF-SED and HF-RW. HF diet was terminated at PND 35 and all offspring were placed on CD. Body weight and %fat of dams were greatest in order; HF-SED > HF-RW > CD-SED > CD-RW. Adult offspring were exposed to O 3 for two consecutive days (0.8 ppm, 4 h/day). Glucose tolerance tests (GTT), ventilatory parameters (plethysmography), and bronchoalveolar fluid (BALF) cell counts and protein biomarkers were performed to assess response to O 3 . Exercise and diet altered body weight and %fat of young offspring. GTT, ventilation and BALF cell counts were exacerbated by O 3 with responses markedly exacerbated in males. HF diet and O 3 led to significant exacerbation of several BALF parameters: total cell count, neutrophils and lymphocytes were increased in male HF-SED versus CD-SED. Males were hyperglycemic after O 3 exposure and exhibited exacerbated GTT responses. Ventilatory dysfunction was also exacerbated in males. Maternal exercise had minimal effects on O 3 response. The results of this exploratory study suggest a link between maternal obesity and susceptibility to O 3 in their adult offspring in a sex-specific manner.

Purpose: To compare outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) when an experienced DSAEK surgeon transitions to DMEK while following 2 published endothelial keratoplasty surgical techniques., Methods: This is a retrospective review of 200 eyes of 132 patients with Fuchs corneal dystrophy that underwent endothelial keratoplasty performed by one surgeon. Published, standardized techniques were followed for both DSAEK and DMEK. Postoperative complications were recorded. Best spectacle-corrected visual acuity (BSCVA), intraocular pressure, and central endothelial cell loss (ECL) were evaluated at 6 months postoperatively., Results: There were no intraoperative complications. One DSAEK and 5 DMEK grafts developed graft detachment requiring rebubbling (P = 0.097). No iatrogenic primary graft failures occurred in the DSAEK group compared with one in the DMEK group. No pupil block episodes occurred in the DSAEK group compared with one in the DMEK group. Posterior synechiae formation occurred 15 times in the DMEK group and did not occur in the DSAEK group (P < 0.001). At 6 months, BSCVA was better in the DMEK group than in the DSAEK group (20/24; logMAR = 0.0844-20/32; logMAR = 0.2063) (P < 0.001). More eyes reached 20/20 or better BSCVA in the DMEK group compared with DSAEK (54.5%-13%) (P < 0.011). At 6 months, ECL was higher in the DMEK group than in the DSAEK group (31.9%-19.9%) (P < 0.001)., Conclusions: Complications can be minimized and excellent outcomes can be achieved, without a steep learning curve, when an experienced DSAEK surgeon transitions to DMEK following a standardized technique. Six-month vision outcomes are better in the DMEK group; however, the rate of a newly described complication, posterior synechiae formation, and 6-month ECL are higher in the DMEK group than in the DSAEK group.

The prevalence of a sedentary (SED) life style combined with calorically rich diets has spurred the rise in childhood obesity, which, in turn, translates to adverse health effects in adulthood. Obesity and lack of active (ACT) lifestyle may increase susceptibility to air pollutants. We housed 22-day-old female Long-Evans rats in a cage without (SED) or with a running wheel (ACT). After 10 wk the rats ran 310 ± 16.3 km. Responses of SED and ACT rats to whole-body O 3 (0, 0.25, 0.5, or 1.0 ppm; 5 h/day for 2 days) was assessed. Glucose tolerance testing (GTT) was performed following the first day of O 3 ACT rats had less body fat and an improved glucose GTT. Ventilatory function (plethysmography) of SED and ACT groups was similarly impaired by O 3 Bronchoalveolar lavage fluid (BALF) was collected after the second O 3 exposure. SED and ACT rats were hyperglycemic following 1.0 ppm O 3 GTT was impaired by O 3 in both groups; however, ACT rats exhibited improved recovery to 0.25 and 1.0 ppm O 3 BALF cell neutrophils and total cells were similarly increased in ACT and SED groups exposed to 1.0 ppm O 3 O 3 -induced increase in eosinophils was exacerbated in SED rats. Chronic exercise from postweaning to adulthood improved some of the metabolic and pulmonary responses to O 3 (GTT and eosinophils) but several other parameters were unaffected. The reduction in O 3 -induced rise in BALF eosinophils in ACT rats suggests a possible link between a SED lifestyle and incidence of asthma-related symptoms from O 3 ., (Copyright © 2017 the American Physiological Society.)

Epidemiological data suggest that a sedentary lifestyle may contribute to increased susceptibility for some environmental toxicants. We developed an animal model of active versus sedentary life style by providing female Sprague-Dawley rats with continuous access to running wheels. Sedentary rats were housed in standard cages without wheels. After training for 12 wks, rats were exposed to 0, 0.25, 0.5 or 1.0 ppm ozone [O3 for 5 h/d, 1 d/wk, for 6 wk (N = 10 per group)]. Body composition (%fat, lean and fluid) was monitored noninvasively over the course of the study. Ventilatory parameters [tidal volume, minute ventilation, frequency and enhanced pause (Penh)] were assessed using whole-body plethysmography prior to O3 and 24 h after the 5th O3 exposure. Trained rats lost ∼2% body fat after 12 wk of access to running wheels. Peak wheel activity was reduced by 40% after exposure to 1.0 ppm O3. After the 5th O3 exposure, body weight and %fat were reduced in sedentary but not trained rats. Penh was significantly elevated in sedentary but not trained rats the day after exposure to 1.0 ppm O3. However, lung lavage cell counts and biomarkers of pulmonary inflammation measured 1 day after the final exposure were inconsistently affected by training. Wheel running led to marked physiological responses along with some indication of improved pulmonary recovery from O3 exposure. However, wheel running with O3 exposure may also be a detriment for some pulmonary endpoints. Overall, a sedentary lifestyle may increase susceptibility to O3, but additional studies are needed.

Ozone (O3) is known to induce adverse pulmonary and systemic health effects. Importantly, children and older persons are considered at-risk populations for O3-induced dysfunction, yet the mechanisms accounting for the age-related pulmonary responses to O3 are uncertain. In this study, we examined age-related susceptibility to O3 using 1 mo (adolescent), 4 mo (young adult), 12 mo (adult) and 24 mo (senescent) male Brown Norway rats exposed to filtered air or O3 (0.25 and 1.00 ppm), 6 h/day, two days/week for 1 week (acute) or 13 weeks (subchronic). Ventilatory function, assessed by whole-body plethysmography, and bronchoalveolar lavage fluid (BALF) biomarkers of injury and inflammation were used to examine O3-induced pulmonary effects. Relaxation time declined in all ages following the weekly exposures; however, this effect persisted only in the 24 mo rats following a five days recovery, demonstrating an inability to induce adaptation commonly seen with repeated O3 exposures. PenH was increased in all groups with an augmented response in the 4 mo rats following the subchronic O3 exposures. O3 led to increased breathing frequency and minute volume in the 1 and 4 mo animals. Markers of pulmonary permeability were increased in all age groups. Elevations in BALF γ-glutamyl transferase activity and lung inflammation following an acute O3 exposure were noted in only the 1 and 4 mo rats, which likely received an increased effective O3 dose. These data demonstrate that adolescent and young adult animals are more susceptible to changes in ventilation and pulmonary injury/inflammation caused by acute and episodic O3 exposure.

Diet-induced obesity has been suggested to lead to increased susceptibility to air pollutants such as ozone (O3); however, there is little experimental evidence. Thirty day old male and female Brown Norway rats were fed a normal, high-fructose or high-fat diet for 12 weeks and then exposed to O3 (acute - air or 0.8 ppm O3 for 5 h, or subacute - air or 0.8 ppm O3 for 5 h/d 1 d/week for 4 weeks). Body composition was measured non-invasively using NMR. Ventilatory parameters and exploratory behavior were measured after the third week of subacute exposure. Bronchoalveolar lavage fluid (BALF) and blood chemistry data were collected 18 h after acute O3 and 18 h after the fourth week of subacute O3. The diets led to increased body fat in male but not female rats. O3-induced changes in ventilatory function were either unaffected or improved with the fructose and fat diets. O3-induced reduction in exploratory behavior was attenuated with fructose and fat diets in males and partially in females. O3 led to a significant decrease in body fat of males fed control diet but not the fructose or fat diet. O3 led to significant increases in BALF eosinophils, increase in albumin, and reductions in macrophages. Female rats appeared to be more affected than males to O3 regardless of diet. Overall, treatment with high-fructose and high-fat diets attenuated some O3 induced effects on pulmonary function, behavior, and metabolism. Exacerbation of toxicity was observed less frequently.

Time-domain nuclear magnetic resonance (TD-NMR)-based measurement of body composition of rodents is an effective method to quickly and repeatedly measure proportions of fat, lean, and fluid without anesthesia. TD-NMR provides a measure of free water in a living animal, termed %fluid, and is a measure of unbound water in the vascular and extracellular spaces. We hypothesized that injecting a bolus of fluid into the peritoneal cavity would lead to an abrupt increase in %fluid and the rate of clearance monitored with TD-NMR would provide a noninvasive assessment of the free water homeostasis in an awake rat. Several strains of laboratory rats were injected intraperitoneally with 10 ml/kg isotonic or hypertonic saline and %fluid was monitored repeatedly with a Bruker "Minispec" TD-NMR body composition system. Following isotonic saline, %fluid increased immediately by 0.5% followed by a recovery over ∼6 h. Injecting hypertonic (3 times normal saline) resulted in a significantly greater rise in %fluid and longer recovery. Intraperitoneal and subcutaneous fluid injection led to similar rates of clearance. The Wistar-Kyoto rat strain displayed significantly slower recovery to fluid loads compared with Long-Evans and Sprague-Dawley strains. Rats exercised chronically showed significant increases in %fluid, but the rate of clearance of fluid was similar to that of sedentary animals. We conclude that this technique could be used to study vascular and extracellular volume homeostasis noninvasively in rats.

Body fat serves as a storage compartment for lipophilic pollutants and affects the pharmacokinetics of many toxic chemicals. Understanding how body fat varies with gender, strain, and age may be essential for development of experimental models to study mechanisms of toxicity. Nuclear magnetic resonance (NMR)-based analysis serves as a noninvasive means of assessing proportions of fat, lean, and fluid in rodents over their lifetime. The aim of this study was to track changes in body composition of male and female Long-Evans (LE), Sprague-Dawley (SD), Fischer (F334), and Brown Norway (BN) rats from postweaning over a >2-yr period. Percent fat of preweaned LE and SD rats was markedly higher compared to the other strains. LE and SD strains displayed marked increases in body fat from weaning to 8 mo of age. Postweaned F344 male and females showed relatively low levels of percent fat; however, at 2 yr of age percent fat of females was equal to that of SD and LE in females. BN rats showed the highest levels of lean tissue and lowest levels of fat. Percent fat of the BN strain rose at the slowest rate as they aged. Percent fluid was consistently higher in males for all strains. Females tended to have higher percent fat than males in LE, SD, and F344 strains. Assessing changes in body fat as well as lean and fluid of various strains of male and female rats over their lifetime may prove useful in many research endeavors, including pharmacokinetics of lipophilic toxicants, mechanisms underlying obesity, and metabolic disorders.

Chronic exercise is considered as one of the most effective means of countering symptoms of the metabolic syndrome (MS) such as obesity and hyperglycemia. Rodent models of forced or voluntary exercise are often used to study the mechanisms of MS and type 2 diabetes. However, there is little known on the impact of genetic strain on the metabolic response to exercise. We studied the effects of housing rats with running wheels (RW) for 65 days compared to sedentary (SED) housing in five female rat strains: Sprague-Dawley (SD), Long-Evans (LE), Wistar (WIS), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY). Key parameters measured were total distance run, body composition, food consumption, motor activity, ventilatory responses by plethysmography, and resting metabolic rate (MR). WKY and SHR ran significantly more than the WIS, LE, and SD strains. Running-induced reduction in body fat was affected by strain but not by distance run. LE's lost 6% fat after 21 d of running whereas WKY's lost 2% fat but ran 40% more than LE's. LE and WIS lost body weight while the SHR and WKY strains gained weight during running. Food intake with RW was markedly increased in SHR, WIS, and WKY while LE and SD showed modest increases. Exploratory motor activity was reduced sharply by RW in all but the SD strain. Ventilatory parameters were primarily altered by RW in the SHR, WKY, and WIS strains. MR was unaffected by RW. In an overall ranking of physiological and behavioral responses to RW, the SD strain was considered the least responsive whereas the WIS was scored as most responsive. In terms of RW-induced fat loss, the LE strain appears to be the most ideal. These results should be useful in the future selection of rat models to study benefits of volitional exercise., (Published by Elsevier Inc.)

New Findings: What is the central question of this study? How do lean and obese rats respond physiologically to caloric restriction? What is the main finding and its importance? Obese rats show marked benefits compared with lean animals. Reduced body fat is associated with improved longevity with caloric restriction (CR) in rodents. Little is known regarding effects of CR in genetically lean versus obese strains. Long-Evans (LE) and Brown Norway (BN) rats make an ideal comparison for a CR study because the percentage body fat of young adult LE rats is double that of BN rats. Male LE and BN rats were either fed ad libitum (AL) or were calorically restricted to 80 or 90% of their AL weight. The percentages of fat, lean and fluid mass were measured non-invasively at 2- to 4-week intervals. Metabolic rate and respiratory quotient were measured after 3, 6, 9 and 12 months of CR. Overall health was scored monthly. The percentage of fat of the LE strain decreased with CR, whereas the percentage of fat of the BN strain remained above the AL group for several months. The percentage of lean mass increased above the AL for both strains subjected to CR. The percentage of fluid was unaffected by CR. The average metabolic rate over 22 h of the BN rats subjected to CR was reduced, whereas that of LE rats was increased slightly above the AL group. The respiratory quotient of BN rats was decreased with CR. Overall health of the CR LE group was significantly improved compared with that of the AL group, whereas health of the CR BN rats was impaired compared with the AL group. Overall, the lean BN and obese LE strains differ markedly in fat utilization and metabolic response to prolonged CR. There appears to be little benefit of CR in the lean strain., (Published 2015. This article is a U.S. Government work and is in the public domain in the USA.)

Tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) and tris(2-chloro-2-ethyl)phosphate (TCEP) are organophosphorous flame retardants with widespread usage and human exposures through food, inhalation, and dust ingestion. They have been detected in human tissues including urine and breast milk. Reports of disrupted neural growth in vitro, abnormal development in larval zebrafish, and altered thyroid hormones in several species have raised concern for neurodevelopmental toxicity. This is especially the case for TDCIPP, which is more potent and has more activity in those assays than does TCEP. We evaluated the potential for developmental neurotoxicity of TDCIPP and TCEP in a mammalian model. Pregnant Long-Evans rats were administered TDCIPP (15, 50, or 150 mg/kg/day) or TCEP (12, 40, 90 mg/kg/day) via oral gavage from gestational day 10 to weaning. Corn oil was the vehicle control in both studies. Body weight and righting reflex development were monitored in all pups. A subset of offspring at culling and weaning, and dams at weaning, were sacrificed for serum and organ collection for measurement of brain, liver, and thyroid weights, serum thyroid levels, and serum and brain acetylcholinesterase activities. Brain weights were also measured in a group of adult TDCIPP-treated offspring. One male and one female from each litter were allocated for behavioral testing at several ages: standard locomotor activity (preweaning, postweaning, adults), locomotor activity including a lighting change mid-way (postweaning, adults), elevated zero maze (postweaning, adults), functional observational battery (FOB; postweaning, adults), and Morris water maze (place learning, reference and working memory; adults). Neither chemical produced changes in maternal body weight or serum thyroid hormones, but relative liver weight was increased at the high doses of both TDCIPP and TCEP. In offspring, there were no effects on viability, litter size, or birth weight. With TDCIPP, absolute liver weights were lower at weaning and weight gain was lower in the high-dose offspring until about two months of age. Thyroid hormones and brain weights were not altered and acetylcholinesterase (both brain and serum) was not inhibited by either chemical. TDCIPP-treated offspring showed slight differences in floating in the water maze, hindlimb grip strength, and altered activity habituation, whereas TCEP-treated rats showed differences in quadrant time (probe) and middle-zone preference in the water maze. Regarding these few changes, the effects were minimal, mostly not related to dose, and did not appear treatment-related or biologically significant. Overall, these data do not support the potential for thyrotoxicity or developmental neurotoxicity produced by TDCIPP or TCEP., (Published by Elsevier Inc.)

Factors impacting life stage-specific sensitivity to chemicals include toxicokinetic and toxicodynamic changes. To evaluate age-related differences in the biochemical and behavioral impacts of two typical N-methyl carbamate pesticides, we systematically compared their dose-response and time-course in preweanling (postnatal day, PND, 18) and adult male Brown Norway rats (n=9-10/dose or time) ranging from adolescence to senescence (1, 4, 12, 24 mo). Carbaryl was administered orally at 3, 7.5, 15, or 22.5mg/kg and data were collected at 40 min after dosing, or else given at 3 or 15 mg/kg and data collected at 30, 60, 120, and 240 min. Methomyl was studied only in adult and senescent rat (4, 12, 24 mo) in terms of dose-response (0.25. 0.6, 1.25, 2.5mg/kg) and time-course (1.25mg/kg at 30, 60, 120, 240 min). Motor activity as well as brain and erythrocyte (RBC) cholinesterase (ChE) activity were measured in the same animals. In the carbaryl dose-response, PND18 rats were the most sensitive to the brain ChE-inhibiting effects of carbaryl, but 12- and 24-mo rats showed more motor activity depression even at similar levels of brain ChE inhibition. We have previously reported that brain ChE inhibition, but not motor activity effects, closely tracked carbaryl tissue levels. There were no age-related differences in methomyl-induced ChE inhibition across doses, but greater motor activity depression was again observed in the 12- and 24-mo rats. Carbaryl time-course data showed that motor activity depression reached a maximum later, and recovered slower, in the 12- and 24-mo rats compared to the younger ages; slowest recovery and maximal effects were seen in the 24-mo rats. Acetylcholinesterase sensitivity (concentration-inhibition curves) was measured in vitro using control tissues from each age. Inhibitory concentrations of carbaryl were somewhat lower in PND18, 12-, and 24-mo tissues compared to 1- and 4-mo, but there were no differences with methomyl-treated tissues. Thus, in the dose-response and time-course, there were dissociations between brain ChE inhibition and the magnitude as well as recovery of motor activity changes. The explanation for this dissociation is unclear, and is likely due to early development followed by aging-related decline in both kinetic parameters and neurological responsiveness., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Setting exposure standards for environmental pollutants may consider the aged as a susceptible population but the few published studies assessing susceptibility of the aged to air pollutants are inconsistent. Episodic ozone (O₃) is more reflective of potential exposures occurring in human populations and could be more harmful to the aged. This study used radiotelemetry to monitor heart rate (HR), core temperature (T(c)) and motor activity (MA) in adult (9-12 months) and senescent (20-24 months) male, Brown Norway rats exposed to episodic O₃ (6 h/day of 1 ppm O₃ for 2 consecutive days/week for 13 weeks). Acute O₃ initially led to marked drops in HR and T(c). As exposures progressed each week, there was diminution in the hypothermic and bradycardic effects of O₃. Senescent rats were less affected than adults. Acute responses were exacerbated on the second day of O₃ exposure with adults exhibiting greater sensitivity. During recovery following 2 d of O₃, adult and senescent rats exhibited an elevated T(c) and HR during the day but not at night, an effect that persisted for at least 48 h after O₃ exposure. MA was elevated in adults but not senescent rats during recovery from O₃. Overall, acute effects of O₃, including reductions in HR and T(c), were attenuated in senescent rats. Autonomic responses during recovery, included an elevation in T(c) with a pattern akin to that of a fever and rise in HR that were independent of age. An attenuated inflammatory response to O₃ in senescent rats may explain the relatively heightened physiological response to O₃ in younger rats.

Air pollutants have been associated with increased diabetes in humans. We hypothesized that ozone would impair glucose homeostasis by altering insulin signaling and/or endoplasmic reticular (ER) stress in young and aged rats. One, 4, 12, and 24 month old Brown Norway (BN) rats were exposed to air or ozone, 0.25 or 1.0 ppm, 6 h/day for 2 days (acute) or 2 d/week for 13 weeks (subchronic). Additionally, 4 month old rats were exposed to air or 1.0 ppm ozone, 6 h/day for 1 or 2 days (time-course). Glucose tolerance tests (GTT) were performed immediately after exposure. Serum and tissue biomarkers were analyzed 18 h after final ozone for acute and subchronic studies, and immediately after each day of exposure in the time-course study. Age-related glucose intolerance and increases in metabolic biomarkers were apparent at baseline. Acute ozone caused hyperglycemia and glucose intolerance in rats of all ages. Ozone-induced glucose intolerance was reduced in rats exposed for 13 weeks. Acute, but not subchronic ozone increased α2-macroglobulin, adiponectin and osteopontin. Time-course analysis indicated glucose intolerance at days 1 and 2 (2>1), and a recovery 18 h post ozone. Leptin increased day 1 and epinephrine at all times after ozone. Ozone tended to decrease phosphorylated insulin receptor substrate-1 in liver and adipose tissues. ER stress appeared to be the consequence of ozone induced acute metabolic impairment since transcriptional markers of ER stress increased only after 2 days of ozone. In conclusion, acute ozone exposure induces marked systemic metabolic impairments in BN rats of all ages, likely through sympathetic stimulation., (© 2013.)

Purpose: To evaluate the influence of preoperative graft thickness (GT) on final visual acuity and speed of vision recovery after Descemet stripping automated endothelial keratoplasty (DSAEK)., Methods: The best spectacle-corrected acuity (BSCVA) was measured after DSAEK was performed at 1, 3, 6, 12, and 24 months. A regression analysis was performed to determine whether GT predicted the BSCVA across each time gate. The time to achieve the "1-year maximum BSCVA" was determined to assess the "speed" of recovery for all eyes that had data at 1, 3, 6, and 12 months. Additionally, the final BSCVA was compared between 2 distinct groups of "thin" (<125-μm) versus "thick" (>165-μm) tissue., Results: There were 144 eyes evaluated. No significant correlations were found between the GT and the BSCVA at any of the time gates: 1, 3, 6, 12, or 24 months. Speed of vision recovery was not affected by the GT. The average GT values of the eyes that achieved BSCVA by 1, 3, 6 months and 1 year were not significantly different and were 154.7, 141.3, 149, and 150.1 μm, respectively. No difference was found between the BSCVA of "thick" versus "thin" tissues at any of the time gates: 1, 3, 6, or 12 months., Conclusions: Preoperative GT measurements were not correlated with the BSCVA after the DSAEK was performed at 1, 6, 12, or 24 months postoperatively and do not determine the speed of vision recovery. Additionally, no difference was found in postoperative vision outcomes when directly comparing tissues at either end of the GT spectrum of this study.

Type I diabetes mellitus (TID) results from the autoimmune destruction of the insulin-producing pancreatic β-cells. Gene therapy is one strategy being actively explored to cure TID by affording non-β-cells the ability to secrete insulin in response to physiologic stimuli. In previous studies, we used a novel surgical technique to express furin-cleavable human insulin (INS-FUR) in the livers of streptozotocin (STZ)-diabetic Wistar rats and nonobese diabetic (NOD) mice with the use of the HMD lentiviral vector. Normoglycemia was observed for 500 and 150 days, respectively (experimental end points). Additionally, some endocrine transdifferentiation of the liver, with storage of insulin in granules, and expression of some β-cell transcription factors (eg, Pdx1, Neurod1, Neurog3, Nkx2-2, Pax4) and pancreatic hormones in both studies. The aim of this study was to determine if this novel approach could induce liver to pancreatic transdifferentiation to reverse diabetes in pancreatectomized Westran pigs. Nine pigs were used in the study, however only one pig maintained normal fasting blood glucose levels for the period from 10 to 44 days (experimental end point). This animal was given 2.8 × 10(9) transducing units/kg of the lentiviral vector expressing INS-FUR. A normal intravenous glucose tolerance test was achieved at 30 days. Reverse-transcription polymerase chain reaction analysis of the liver tissue revealed expression of several β-cell transcription factors, including the key factors, Pdx-1 and Neurod1, pancreatic hormones, glucagon, and somatostatin; however, endogenous pig insulin was not expressed. Triple immunofluorescence showed extensive insulin expression, as was previously observed in our studies with rodents. Additionally, a small amount of glucagon and somatostatin protein expression was seen. Collectively, these data indicate that pancreatic transdifferentiation of the liver tissue had occurred. Our data suggest that this regimen may ultimately be used clinically to cure TID, however more work is required to replicate the successful reversal of diabetes in increased numbers of pigs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: We investigated whether graft produced anti-human CD2, mediated by adenovirus (Adv) transduction of pig neonatal islet cell clusters (pNICC), would protect xenografts in a humanized mouse model from immune attack and whether such immunosuppression would remain local., Methods: A mouse anti-human CD2 Ab (CD2hb11) previously generated by us was genetically engineered to produce chimeric and humanized versions. The three forms of CD2hb11 were named dilimomab (mouse), diliximab (chimeric) and dilizumab (humanized). All 3 forms of CD2hb11 Ab were tested for their ability to bind CD3(+) human T cells and to inhibit a human anti-pig xenogeneic mixed lymphocyte reaction (MLR). They were administered systemically in a humanized mouse model in order to test their ability to deplete human CD3(+) T cells and whether they induced a cytokine storm. An adenoviral vector expressing diliximab was generated for transduction of pNICC. Humanized mice were transplanted with either control-transduced pNICC or diliximab-transduced pNICC and human T cells within grafts and spleens were enumerated by flow cytometry., Results: Dilimomab and diliximab inhibited a human anti-pig xenogeneic response but dilizumab did not. All 3 forms of CD2hb11 Ab bound human T cells in vitro though dilimomab and diliximab exhibited 300-fold higher avidity than dilizumab. All 3 anti-CD2 Abs could deplete human CD3(+) T cells in vivo in a humanized mouse model without inducing upregulation of activation markers or significant release of cytokines. Humanized mice transplanted with diliximab-transduced pNICC afforded depletion of CD3(+) T cells at the graft site leaving the peripheral immune system intact., Conclusions: Local production of a single Ab against T cells can reduce graft infiltration at the xenograft site and may reduce the need for conventional, systemic immunosuppression., (© 2013 John Wiley & Sons A/S.)

Background: Slipped capital femoral epiphysis is a condition with potentially severe complications. Controversy remains as to when to undertake prophylactic pinning. We aimed to assess the utility of the posterior sloping angle as a predictor for contralateral slip in a large, multi-ethnic cohort including Polynesian children with a high incidence of slipped capital femoral epiphysis., Methods: All patients presenting to our hospital between 2000 and 2009 were identified and records were reviewed to determine demographic data and determine whether they subsequently developed a contralateral slip. The presenting radiographs were reviewed and the posterior sloping angle was measured. Patients with bilateral slips at presentation and those without initial radiographs were excluded., Results: Records and radiographs of 132 patients were analyzed for the posterior sloping angle in the unaffected hip. Forty-two patients who had subsequently developed a contralateral slip had a mean posterior sloping angle (and standard deviation) of 17.2° ± 5.6°, which was significantly higher (p < 0.001) than that of 10.8° ± 4.2° for the ninety patients who had had a unilateral slip. Children who had developed a subsequent contralateral slip were significantly younger (11.1 years) than those who had developed a unilateral slip (12.2 years) (p < 0.001). If a posterior sloping angle of 14° were used as an indication for prophylactic fixation in this population, thirty-five (83.3%) of forty-two contralateral slips would have been prevented, and nineteen (21.1%) of ninety hips would have been pinned unnecessarily. The number needed to treat to prevent one subsequent contralateral slip is 1.79., Conclusions: To our knowledge, this is the largest study to date that confirms that the posterior sloping angle is a reliable predictor of contralateral slip and can be used to guide prophylactic pinning. The posterior sloping angle is applicable in the high-risk Polynesian population and could be useful in preventing future slips in populations that are difficult to follow up.

Studies incorporating both toxicokinetic and dynamic factors provide insight into chemical sensitivity differences across the life span. Tissue (brain, plasma, liver) levels of the N-methyl carbamate carbaryl, and its metabolite 1-naphthol, were determined and related to brain and RBC cholinesterase (ChE) inhibition in the same animals. Dose-response (3, 7.5, 15, or 22.5 mg/kg, 40-45 min postdosing) and time course (3 or 15 mg/kg at 30, 60, 120, or 240 min postdosing) of acute effects of carbaryl (oral gavage) in preweanling (postnatal day [PND] 18) and adult male Brown Norway rats from adolescence to senescence (1, 4, 12, 24 mo) were compared. At all ages there were dose-related increases in carbaryl and 1-naphthol in the dose-response study, and the time-course study showed highest carbaryl levels at 30 min postdosing. There were, however, age-related differences in that the 1- and 4-mo rats showed the lowest levels of carbaryl and 1-naphthol, and PND18 and 24-mo rats had similar, higher levels. The fastest clearance (shortest half-lives) was observed in 1- and 4-mo rats. Carbaryl levels were generally higher than 1-naphthol in brain and plasma, but in liver, 1-naphthol levels were similar to or greater than carbaryl. Brain ChE inhibition closely tracked brain carbaryl concentrations regardless of the time after dosing, but there was more variability in the relationship between RBC ChE and plasma carbaryl levels. Within-subject analyses suggested somewhat more brain ChE inhibition at lower carbaryl levels only in the PND18 rats. These findings may reflect maturation followed by decline in kinetic factors over the life span.

Purpose: To evaluate the endothelial cell survival and stromal bed quality when creating deep stromal cuts with a low-pulse energy, high-frequency femtosecond laser to produce "ultrathin" tissue for Descemet stripping automated endothelial keratoplasty., Methods: Seventeen corneas were used for this study. Five corneas were cut with the laser at a depth of 420 to 500 μm to produce a tissue thickness of approximately ≤70 μm. Five corneas served as an uncut comparison group. Vital dye staining and computer digitized planimetry analysis were performed on these corneas. The 7 remaining corneas were cut for scanning electron microscopy evaluation., Results: The mean central posterior stromal thickness of cut corneas was 60.6 μm (range, 43-72 μm). Endothelial cell damage in cut and comparison corneas was 3.92% ± 2.22% (range, 1.71%-6.51%) and 4.15% ± 2.64% (range, 1.21%-7.01%), respectively (P = 0.887). Low-magnification (×12) scanning electron microscopy revealed a somewhat irregular-appearing surface with concentric rings peripherally. Qualitative grading of higher magnification (×50) central images resulted in an average score of 2.56 (between smooth and rough)., Conclusions: Ultrathin tissue for Descemet stripping automated endothelial keratoplasty can be safely prepared with minimal endothelial cell damage using a low-pulse energy, high-frequency femtosecond laser; however, the resulting stromal surface quality may not be optimal with this technique.

Purpose: To determine the outcomes and complication rates achieved by a novice cornea surgeon when performing Descemet stripping automated endothelial keratoplasty (DSAEK) while precisely following a previously described forceps insertion technique., Methods: Prospective, noncomparative interventional case series including 100 eyes of 74 patients with endothelial decompensation. An institutional review board approved, prospective, DSAEK series was initiated. Cases included all initial patients with endothelial failure operated on by a single surgeon after his cornea fellowship training. The surgeon strictly adhered to a previously published 5-mm incision, folded forceps graft insertion technique. Patients were followed at 1 day, 1 week, and 1, 3, and 6 months. Postoperative complications (including graft dislocation, primary graft failure, and pupillary block), best spectacle-corrected visual acuity (BSCVA) and specular microscopy of central endothelial cell density at 6 months postoperatively were the main outcome measures., Results: One hundred consecutive eyes were enrolled in the study, and 100% follow-up at 6 months was achieved. Postoperative complications included 2 graft dislocations (2%), and both grafts were attached successfully and cleared; 2 episodes of cystoid macular edema (2%) occurred, and 1 eye (1%) developed areas of anterior iris synechiae to the graft. There were no pupillary block episodes or primary graft failures. In eyes without comorbidity (n=57), the mean BSCVA improved from 20/48 preoperation to 20/29 at 6 months after operation (P<0.001). No eyes lost vision. Mean central endothelial cell density decreased from 2769 cells per square millimeter preoperatively to 2308 cells per square millimeter postoperatively at 6 months. This represented a mean cell loss of 16%., Conclusions: This study demonstrates that with meticulous attention to a standardized forceps insertion technique, excellent outcomes with low rates of complications, improved BSCVA, and low endothelial cell loss can be achieved with DSAEK surgery.

Pseudomeningocoele is a recognised complication of spinal surgery. It could be either asymptomatic or symptomatic. We present a 63-year-old male who developed a delayed pseudomeningocoele and symptomatic transdural herniation and strangulation of the cauda equinae following resection of a Myxopapillary ependymoma. He underwent successful operative re-exploration, un-tethering of the cauda equinae and re-closure of the dural defect with resolution of his symptoms. We discuss the clinical features, operative technical factors involved and the essential importance of neuroimaging with critical analysis of the imaging findings and correlation of the clinical symptoms, when such a diagnosis is being considered.

A systematic analysis of defect textures in faceted nanoparticles with polygonal configurations embedded in a nematic matrix is performed using the Landau-de Gennes model, homeotropic strong anchoring in a square domain with uniform alignment in the outer boundaries. Defect and textures are analyzed as functions of temperature T, polygon size R, and polygon number N. For nematic nanocomposites, the texture satisfies a defect charge balance equation between bulk and surface (particle corner) charges. Upon decreasing the temperature, the central bulk defects split and together with other -1/2 bulk defects are absorbed by the nanoparticle's corners. Increasing the lattice size decreases confinement and eliminates bulk defects. Increasing the polygon number increases the central defect charge at high temperature and the number of surface defects at lower temperatures. The excess energy per particle is lower in even than in odd polygons, and it is minimized for a square particle arrangement. These discrete modeling results show for first time that, even under strong anchoring, defects are attached to particles as corner defects, leaving behind a low energy homogeneous orientation field that favors nanoparticle ordering in nematic matrices. These new insights are consistent with recent thermodynamic approaches to nematic nanocomposites that predict the existence of novel nematic/crystal phases and can be used to design nanocomposites with orientational and positional order.

Purpose: To describe a new technique for handling Descemet stripping automated endothelial keratoplasty (DSAEK) specimens intraoperatively and during processing., Methods: The processing method begins by adding a drop of eosin to the specimen intraoperatively, followed by submersion in 10% formalin solution. The specimen appears reddish, allowing for easy identification and is floated onto an immersed slide to maintain an unfolded flattened specimen. After bisection, one half is stained with hematoxylin and eosin and covered with a cover slip, whereas the other half is transferred to filter paper and a cassette and is submitted for paraffin embedding on the cut edge., Results: The technique reduces the chances of a specimen not surviving processing. The new method also allows for 2 views of DSAEK specimens, both topographical and cross-sectional, thus permitting analysis of endothelial cell density, spatial distribution of cells and guttae, endothelial cell count, and thickness measurements., Conclusions: A novel technique for handling DSAEK specimens to prevent loss and folding, while also allowing for cross-sectional and topographical viewing is reported.

The rapid growth of the aging human population highlights the need for laboratory animal models to study the basic biologic processes of aging and susceptibility to disease, drugs, and environmental pollutants. Methods are needed to evaluate the health of aging animals over time, particularly methods for efficiently monitoring large research colonies. Here we describe an observational assessment method that scores appearance, posture, mobility, and muscle tone on a 5-point scale that can be completed in about 1 min. A score of 1 indicates no deterioration, whereas a score of 5 indicates severe deterioration. Tests were applied to male Brown Norway rats between 12 and 36 mo of age (n = 32). The rats were participating concurrently in experiments on the behavioral effects of intermittent exposure (approximately every 4 mo) to short-acting environmental chemicals. Results demonstrated that aging-related signs of deterioration did not appear before 18 mo of age. Assessment scores and variability then increased with age. Body weights increased until approximately 24 mo, then remained stable, but decreased after 31 mo for the few remaining rats. The incidence of death increased slightly from 20 to 28 mo of age and then rose sharply; median survival age was approximately 30 mo, with a maximum of 36 mo. The results indicate that our observational assessment method supports efficient monitoring of the health of aging rats and may be useful in studies on susceptibility to diseases, drugs, and toxicants during old age.

Purpose: To evaluate the endothelial cell loss at 6 and 12 months after Descemet stripping automated endothelial keratoplasty (DSAEK) using a modified 40/60 underfolding technique and to compare this to the literature on other commonly used implantation techniques, such as the conventional 60/40-fold, gliding, and hitch suture techniques., Methods: Endothelial cell density was measured prospectively, and cell loss was calculated at 6 and 12 months after endothelial keratoplasty using a recently described underfolding implantation technique., Results: In this study, 305 eyes undergoing DSAEK were evaluated. Average endothelial cell loss was 26% at 6 months and 27% at 12 months, all statistically significant reductions from preoperative values (P < 0.01). The decrease in cell count from 6 months to 12 months was not statistically significant., Conclusions: This study demonstrates reduction in endothelial cell loss after DSAEK using the underfold technique when compared with previous reports on conventional folding techniques and similarity to previous reports on glide techniques at 6 and 12 months postoperatively (26% vs. 34% vs. 23% at 6 months). This offers an easy modification to a commonly used existing technique and improves endothelial cell survival after DSAEK.

Purpose: To evaluate the intraoperative and early postoperative outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) in patients with previous glaucoma filtering surgeries., Methods: A retrospective review of all DSAEK surgeries performed at one center comparing complications of DSAEK in eyes with previous glaucoma filtering procedures (study eyes) with a time-matched group of all other DSAEK cases (control eyes)., Results: There were 28 study eyes, 19 with previous trabeculectomies and 9 with previous glaucoma drainage devices (GDDs) and 431 control eyes. Study group intraoperative complications included 1 compromised bleb and 1 loss of donor tissue because of traumatic manipulation. One intraoperative complication, a perforation of the donor tissue, occurred in the control group. Venting stab incisions were used more often in study eyes (n = 5; 18%) than in control eyes (n = 12; 4.4%) (P = 0.002). GDD tubes were trimmed in 2 eyes (22%). No intraoperative manipulations were used to occlude the glaucoma filters or tubes. Postoperative complications in the study group included 1 dislocation (3.6%) and 1 decentered graft (3.6%) and 1 eye with loss of pressure control (3.6%), whereas in the control group, there were 10 dislocations (2.3%) and 1 decentered graft (0.2%) (P = 0.267 for dislocations and P = 0.118 for decentered grafts). One episode of pupillary block (0.2%) occurred in the control group, and none occurred in the study group. No primary graft failures occurred in either group., Conclusions: DSAEK surgeries in eyes with previous glaucoma filtering procedures were performed without primary graft failure and with reasonably low dislocation (3.6%) and graft decentration (3.6%) rates. Although the intraoperative complication rate for the study group (7.1%) was higher than the rate for the control group (0.23%), excellent early postoperative outcomes can be achieved when DSAEK is performed in eyes with previous trabeculectomies and GDDs.

N-Methyl carbamate insecticides are reversible inhibitors of central and peripheral acetylcholinesterase (ChE). Despite their widespread use, there are few studies of neurotoxicity in young animals. To study potential age-related differences, we evaluated seven carbamates (carbaryl, carbofuran, formetanate, methiocarb, methomyl, oxamyl, and propoxur) in preweanling (17 days old or postnatal day [PND] 17) male rats. Motor activity was monitored, and ChE inhibition was measured in brain and red blood cells (RBCs) using a radiometric assay that minimized reactivation of ChE. First, we conducted time-course studies in PND17 Long-Evans male rats, using a single oral dose of each carbamate. Almost all carbamates showed maximal ChE inhibition at a 45-min time point; only methomyl showed an earlier peak effect (15 min). At 24 h, most inhibition had recovered. Next, dose-response data were collected for each carbamate, using four doses and control, with motor activity testing beginning 15 min after dosing and tissue collection at 40-45 min. RBC ChE was generally inhibited to a greater degree than brain. Motor activity was not as sensitive a measure for some of the carbamates, with some differences across carbamates in the shapes of the dose-response curves. Additional studies documented age-related differences by comparing ChE inhibition in PND11, PND17, and adult rats following administration of carbaryl or carbofuran. Only the youngest (PND11) rats were more sensitive than adults to carbaryl, but both younger ages showed more effects than adults with carbofuran. Comparisons of the other carbamates to previous studies in adult rats suggest similar age-related sensitivity. Thus, these data show the time-course and dose-response characteristics for each carbamate and document greater sensitivity of the young for carbofuran and carbaryl.

Purpose: To evaluate complications and clinical outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) with intraocular lens (IOL) exchange compared with DSAEK alone., Design: Retrospective, interventional case series., Methods: DSAEK was performed in 19 eyes in which the anterior chamber IOL was exchanged for a posterior chamber IOL (study group) and in 188 eyes in which the posterior chamber IOL was left in place (comparison group). The complications of graft dislocations, primary graft failure episodes, and pupillary block were recorded for all eyes. Six-month best spectacle-corrected visual acuity and mean central endothelial cell density were measured prospectively and then compared with preoperative values for all eyes., Results: Dislocations occurred in 0 (0%) of 19 eyes in the study group and in 5 (3%) of 188 eyes in the comparison group (P = .47), with 0 primary graft failures and 0 pupillary block episodes in either group. Preoperative mean best spectacle-corrected visual acuity for those eyes without any underlying ocular comorbidities was 20/205 and 20/100 in the study and comparison groups, respectively (P = .18). Mean best spectacle-corrected visual acuity at 6 months improved to 20/48 in the study group and to 20/34 in the comparison group, a statistically significant difference (P = .01). Mean donor cell loss at 6 months was 33% in the study group and 26% in the comparison group (P = .18)., Conclusions: Concurrent IOL exchange with DSAEK surgery does not increase the dislocation, primary graft failure, or pupillary block rates in the immediate postoperative period. Donor endothelial cell loss in DSAEK was not increased significantly by IOL exchange. Visual acuity was slightly worse after combined surgery than after DSAEK alone., ((c) 2010 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to evaluate outcomes of Descemet's stripping automated endothelial keratoplasty (DSAEK) using anterior stromal flawed (ASF) donor corneas that were unsuitable for use in full-thickness penetrating keratoplasty as a result of stromal scars, pterygia, or previous corneal refractive surgery and to compare results with DSAEK using standard tissue., Methods: We conducted a review of our initial 42 (19 with 6-month follow up) consecutive DSAEK surgeries using ASF tissue compared with 357 (199 with 6-month follow up) time-matched controls using standard tissue. Intraoperative and perioperative complications, including dislocations and primary graft failures, were compared. Six-month best spectacle-corrected vision, incidence of rejection episodes, postoperative refractive astigmatism, keratometric values, pre- and postoperative topography-derived surface asymmetry index, and surface regularity index were compared., Results: One surgeon-cut ASF tissue was perforated before surgery and was discarded. No surgeon-cut standard tissue was perforated. No intraoperative complications and no episodes of primary graft failure or pupillary block glaucoma occurred in either group. One (2.4%) postoperative graft dislocation and one (5.2%) graft rejection episode occurred in the study group. There were 10 (2.8%) dislocations and 8 (2.2%) graft rejection in the controls. A statistically similar significant improvement in best spectacle-corrected vision occurred in both groups. Corneal topography, pachymetry, and manifest astigmatism were not significantly different between groups., Conclusion: Postoperative results of DSAEK using donor tissue excluded from use in penetrating keratoplasty as a result of stromal flaws are equivalent to results using standard donor tissue. Central corneal thickness measurements should be performed before cutting to avoid tissue perforation. The use of ASF tissue for DSAEK will expand the cornea donor pool.

Purpose: To compare a 6-month postoperative vision, endothelial cell loss, and immediate postoperative complications in Descemet stripping automated endothelial keratoplasty (DSAEK) cases performed by an experienced corneal surgeon and his inexperienced fellows using an established technique., Design: Retrospective analysis of prospectively gathered data in 327 consecutive DSAEK cases., Methods: DSAEK cases performed by fellows vs attending surgeons during a concurrent period were compared for 6-month postoperative best spectacle-corrected visual acuity (BSCVA), endothelial cell loss, and immediate postoperative complications. This series represents the initial consecutive cases performed by 3 cornea fellows using a technique identical to that used by the attending., Results: After DSAEK, average BSCVA improved from 20/80 to 20/37 in the attending cases and 20/74 to 20/36 in the fellow cases. There was no statistical difference in endothelial cell loss between groups (32% vs 35%). The dislocation rate was 2% in the attending group and 1% in the fellow group. There were no primary graft failures or cases of pupillary block in either group., Conclusions: This study demonstrates no difference in vision or endothelial cell loss after DSAEK when performed by an experienced corneal surgeon or inexperienced fellows. Postoperative complications also were similar. Results and complications of DSAEK performed by supervised novice fellows can equal those of an experienced DSAEK surgeon.

Purpose: To report the immediate postoperative complications and the 6- and 12-month clinical results in a large series of cases undergoing the new triple-procedure Descemet's stripping automated endothelial keratoplasty (DSAEK) and concurrent cataract surgery., Design: Prospective, noncomparative, interventional case series., Participants: Three hundred fifteen eyes of 233 patients with Fuchs' corneal dystrophy were evaluated for the complications of dislocation and iatrogenic primary graft failure (IPGF). Two hundred three eyes of 149 patients had 6-month postoperative data available for other outcome analysis., Methods: A standardized technique of DSAEK with extensive use of cohesive viscoelastic was performed in all 315 eyes with Fuchs' dystrophy, and 225 of those eyes had cataract surgery concurrently. Of the 203 eyes with 6-month data, concurrent phacoemulsification with intraocular lens placement (triple procedure) was performed in 149 of those eyes., Main Outcome Measures: The complications of graft dislocation and IPGF were recorded for all eyes. Six- and 12-month postoperative best spectacle-corrected visual acuity (BSCVA), refractive spherical equivalent (SE), and central donor endothelial cell density (ECD) were measured prospectively and then compared with preoperative values for the triple-procedure eyes., Results: There were 4 dislocations (4%) among the 90 straight DSAEK cases and 4 dislocations (1.8%) among the 225 triple-procedure cases (P = 0.327). There was not a single case of IPGF in any of the 315 DSAEK cases. After the triple procedure, the BSCVA in eyes without comorbidity (n = 122) improved with 93% at 20/40 or better at 6 months and 97% at 20/40 or better at 12 months. Refractive SE at 6 months averaged 0.11+/-1.08 diopters (D), with 73% of eyes within 1 D of emmetropia and 95% within 2 D of emmetropia. The postoperative mean ECD was 1955 cells/mm(2) at 6 months (n = 125) and 1979 cells/mm(2) at 12 months (n = 89) and represented a 32% cell loss from that before surgery (P<0.001) for both postoperative time points., Conclusions: The new triple-procedure DSAEK combined with cataract surgery provides rapid visual recovery and allows selection of an appropriate intraocular lens. Dislocations are rare (1.8%) and primary graft failure did not occur.

Objective: To describe a case of retained host embryonic Descemet membrane (DM) after Descemet stripping automated endothelial keratoplasty (DSAEK)., Methods: Review of clinical findings in a case of DSAEK with retention of host embryonic DM., Results: A geographic and patchy haze in the interface involving the visual axis was noted postoperatively as soon as 1 week after DSAEK surgery. This was noted on clinical exam and thought to be retained embryonic DM. Review of pathology on the explanted DM confirmed delamination of DM with absence of the anterior embryonic layer and only patchy areas of full-thickness DM. The haze was followed over time and did not regress over the first 6 months after surgery. It did not seem to affect vision significantly, and the patient achieved best spectacle-corrected vision of 20/30 by 6 months., Conclusions: Endothelial keratoplasty is a relatively new technique for posterior corneal transplantation. Variations in operative technique continue to be described. Delamination of DM during stripping can occur; however, retention of host embryonic DM in DSAEK surgery seems to be compatible with good vision.

Purpose: To report 6 and 12 month results using precut tissue for Descemet's stripping automated endothelial keratoplasty (DSAEK) and correlate donor characteristics with clinical outcomes., Design: Prospective, noncomparative, interventional case series., Participants: We reviewed 100 donor corneas precut for 100 eyes of 90 DSAEK patients., Methods: Our first 100 consecutive cases of DSAEK with precut tissue were entered into a prospective protocol. Donor characteristics and the visual, refractive, topographic, and specular microscopy results at 6 and 12 months were analyzed. Correlation analysis comparing donor characteristics with clinical outcomes was performed., Main Outcome Measures: Six- and 12-month postoperative best spectacle-corrected visual acuity (BSCVA), refractive astigmatism, topographic keratometry (K), and specular endothelial cell densities (ECD) were measured prospectively and then compared with preoperative values. Donor characteristics analyzed included death to preservation time, death to surgery time, precutting resection to surgery time, and graft thickness., Results: Six months after DSAEK surgery, BSCVA improved from 20/83 to 20/38. (P<0.01). In eyes with no known comorbidity (n = 60), 92% had a vision of >/=20/40 at 6 months and 20% obtained > or =20/20. Astigmatism changed an average of 0.09 diopters (D) and K changed by +0.09 D, both of which were not significant and were stable to 12 months. The postoperative mean ECD (n = 65) was 1918 cells/mm(2) at 6 months, and represented a 31% cell loss from preoperatively (P<0.001). The mean ECD (n = 61) was 1990 cells/mm(2) at 12 months, and represented a 29% cell loss from preoperatively (P<0.001) with no significant change from 6 to 12 months (P = 0.172). Improvement of visual acuity from preoperative to postoperative in eyes without comorbidity was not correlated with any donor characteristic. Greater endothelial cell loss correlated with higher preoperative ECD levels (P<0.001) and with a trend toward longer precut resection to surgery times at both 6 months (P = 0.049) and 12 months (P = 0.051)., Conclusions: Precut tissue by Eye Banks for use in DSAEK surgery provides an improvement in vision with no significant change in astigmatism. Donor endothelial cell loss from 6 to 12 months is stable and is comparable with reports involving tissue that is cut intraoperatively., Financial Disclosure(s): Proprietary or commercial disclosures may be found after the references.