The cellular basis of fetal endoplasmic reticulum stress and oxidative stress in drug-induced neurodevelopmental deficits.

Prenatal substance exposure is a growing public health concern worldwide. Although the opioid crisis remains one of the most prevalent addiction problems in our society, abuse of cocaine, methamphetamines, and other illicit drugs, particularly amongst pregnant women, are nonetheless significant and widespread. Evidence demonstrates prenatal drug exposure can affect fetal brain development and thus can have long-lasting impact on neurobehavioral and cognitive performance later in life. In this review, we highlight research examining the most prevalent drugs of abuse and their effects on brain development with a focus on endoplasmic reticulum stress and oxidative stress signaling pathways. A thorough exploration of drug-induced cellular stress mechanisms during prenatal brain development may provide insight into therapeutic interventions to combat effects of prenatal drug exposure.

Effect of Age-Related Human Lens Sutures Growth on Its Fluid Dynamics.

Purpose: Age-related nuclear cataract is the opacification of the clear ocular lens due to oxidative damage as we age, and is the leading cause of blindness in the world. A lack of antioxidant supply to the core of ever-growing ocular lens could contribute to the cause of this condition. In this project, a computational model was developed to study the sutural fluid inflow of the aging human lens. Methods: Three different SOLIDWORKS computational fluid dynamics models of the human lens (7 years old; 28 years old; 46 years old) were created, based on available literature data. The fluid dynamics of the lens sutures were modelled using the Stokes flow equations, combined with realistic physiological boundary conditions and embedded in COMSOL Multiphysics. Results: The flow rate, volume, and flow rate per volume of fluid entering the aging lens were examined, and all increased over the 40 years modelled. However, while the volume of the lens grew by ∼300% and the flow rate increased by ∼400%, the flow rate per volume increased only by very moderate ∼38%. Conclusions: Here, sutural information from humans of 7 to 46 years of age was obtained. In this modelled age range, an increase of flow rate per volume was observed, albeit at very slow rate. We hypothesize that with even further increasing age (60+ years old), the lens volume growth would outpace its flow rate increases, which would eventually lead to malnutrition of the lens nucleus and onset of cataracts.

Changing trend in the utilisation rate of donated corneas for keratoplasty in the UK: The North East England Study.

PurposeTo report the changing trend in the utilisation rate of donated corneas for keratoplasty and to examine the reasons for unutilised corneas in the North East of England.MethodsRelevant data were retrospectively collected from a local eye retrieval database and the UK Transplant Registry for two separate years; namely, 2006 and 2010.ResultsThe utilisation rate of donated corneas for keratoplasty improved from 57% (52/92) in 2006 to 71% (220/312) in 2010 (P=0.012). Over the same period, there was a marked reduction of failed serological test results from 24% (22/92) to 5% (14/312) (P<0.001). The leading reasons for unutilised corneas were failed serological test results (22/92, 24%) in 2006 and inadequate tissue quality (23/312, 7%) in 2010. The rate of tissue contamination remained similar between 2006 (4%) and 2010 (6%) (P=0.80). Eleven (4%) corneas were not transplanted due to recipient-related factors in 2010. Donor corneas of inadequate tissue quality were associated with older age (P=0.04) but not with gender, donation site, consent method, death-to-enucleation interval, death-to-processing interval, and storage time in the eye bank.ConclusionThere was a substantial improvement in the utilisation rate of corneas donated in the North East of England between 2006 and 2010. The principal reason was a reduction in failed serological test results. High donor age was associated with increased chance of corneas not being used. Utilisation rate of corneas can be further improved if potential modifiable factors are addressed, such as recipient-related factors and microbial contamination.

Review of the Experimental Background and Implementation of Computational Models of the Ocular Lens Microcirculation.

Our sense of vision is critically dependent on the clarity of the crystalline lens. The most common cause of transparency loss in the lens is age-related nuclear cataract, which is due to accumulative oxidative damage to this tissue. Since the ocular lens is an avascular tissue, it has to maintain its physiological homeostasis and antioxidant levels using a system of water microcirculation. This system has been experimentally imaged in animal lenses using different modalities. Based on these data, computational models have been developed to predict the properties of this system in human lenses and its changes due to aging. Although successful in predicting many aspects of lens fluid dynamics, at least in animal models, these in-silica models still need further improvement to become more accurate and representative of human ocular lens. We have been working on gathering experimental data and simultaneously developing computational models of lens microcirculation for the past decade. This review chronologically looks at the development of data-driven computational foundations of lens microcirculation model, its current state, and future advancement directions. A comprehensive model of lens fluid dynamics is essential to understand the physiological optics of this tissue and ultimately the underlying mechanisms of cataract onset and progression.

Impact of telephone consent and potential for eye donation in the UK: the Newcastle Eye Centre study.

AIMS: To examine the impact of telephone consent introduced in 2007 on the eye donation rate and to report the changing trend and potential for improvement in eye donation in Newcastle upon Tyne, UK. METHODS: Relevant data were retrospectively collected from the local eye retrieval database for two separate years, namely, 2006 (before the introduction of telephone consent) and 2010. All the hospitals within Newcastle were included in the study. RESULTS: From 2006 to 2010, there was a 3.5-fold increase in eye donation from 32 (of 2479 deaths) to 111 donors per year (of 2213 deaths) in Newcastle (P<0.001). Consent was obtained via face-to-face interview in all 32 (100%) and 59 (53.2%) donors in 2006 and 2010, respectively. Introduction of telephone consent increased the donation rate by an additional 88.1% (from 59 to 111 donors) in 2010 (P<0.001). In addition, there was a significant increase in medical notes of the deceased being reviewed from 27.1% (671/2479 cases) in 2006 to 62.4% (1382/2213 cases) in 2010 (P<0.001). Acceptance rate of eye donation was 45.7% (32/70) in 2006 and 49.6% (111/224) in 2010 (P=0.575). Acceptance rate was positively associated with registration on organ donor register (P<0.001) and telephone consent (P<0.001), but not with age (P=0.883), gender (P=0.234), or location of death (P=0.984) of the potential donors. CONCLUSION: There has been a substantial improvement in eye donation rate in Newcastle over the recent years. Introduction of telephone consent and high-quality eye donation service serve as effective measures for increasing eye donation.

Physician Perceptions and Beliefs about Generating and Providing a Clinical Summary of the Office Visit.

BACKGROUND: A core measure of the meaningful use of EHR incentive program is the generation and provision of the clinical summary of the office visit, or the after visit summary (AVS), to patients. However, little research has been conducted on physician perceptions and beliefs about the AVS. OBJECTIVES: Evaluate physician perceptions and beliefs about the AVS and the effect of the AVS on workload, patient outcomes, and the care the physician delivers. METHODS: A cross-sectional online survey of physicians at two academic medical centers (AMCs) in the northeast who are participating in the meaningful use EHR incentive program. RESULTS: Of the 1 795 physicians at both AMCs participating in the incentive program, 853 completed the survey for a response rate of 47.5%. Eighty percent of the respondents reported that the AVS was easy (very easy or quite easy or somewhat easy) to generate and provide to patients. Nonetheless, more than three-fourths of the respondents reported a negative effect of generating and providing the AVS on workload of office staff (78%) and workload of physicians (76%). Primary care physicians had more positive beliefs about the effect of the AVS on patient outcomes than specialists (p<0.001) and also had more positive beliefs about the effect of the AVS on the care they delivered than specialists (p<0.001). CONCLUSIONS: Achieving the core meaningful use measure of generating and providing the AVS was easy for physicians but it did not necessarily translate into positive beliefs about the effect of the AVS on patient outcomes or the care the physician delivered. Physicians also had negative beliefs about the effect of the AVS on workload. To promote positive beliefs among physicians around the AVS, organizations should obtain physician input into the design and implementation of the AVS and develop strategies to mitigate its negative impacts on workload.

A 10-year review of orbital biopsy: the Newcastle Eye Centre Study.

PURPOSE: To review the histopathological diagnoses, visual outcome, and complication rate of orbital biopsy in a UK tertiary referral centre. METHODS: This was a retrospective, clinical-pathological, interventional, consecutive case series. All orbital biopsies performed between July 2004 and June 2014 in Newcastle Eye Centre (Newcastle upon Tyne, UK) were included in this study. All relevant data collected from the local electronic database and medical records were analysed. RESULTS: A total of 166 orbital biopsies were identified during the study period: 86 patients (53.1%) were female and the mean age was 53.7 ± 19.7 years. Of all the cases, orbital biopsies were performed unilaterally in 158 (97.5%) patients and bilaterally in 4 (2.5%) patients. The mean follow-up period was 2.2 ± 2.3 years. The two most common histopathological diagnoses were non-specific inflammatory disease (62, 38.3%) and lymphoproliferative disease (40, 24.7%). None of the patients experienced ≥ 2-Snellen line visual loss. There were 7 (4.2%) postoperative complications noted: 1 (0.6%) orbital haemorrhage with no loss of vision, 4 (2.4%) diplopia, 1 (0.6%) short-term symblepharon, and 1 (0.6%) conjunctival granuloma. Postoperative diplopia was associated with lateral orbitotomy (P = 0.044) and excisional biopsy (P = 0.015). CONCLUSIONS: Orbital biopsy serves as a safe diagnostic tool in managing orbital diseases. Patient should be made aware of the risk of postoperative diplopia. Our data provides useful guidance to clinicians when counselling patients for orbital biopsy.

Injuries in recreational curling include head injuries and may be prevented by using proper footwear.

INTRODUCTION: Our study examines a recreational curling population to describe patterns of injury occurrence, estimate risk of injury and to gauge attitudes towards equipment-based prevention strategies. METHODS: In a retrospective case series, we queried the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP), a national injury surveillance database, for curling injuries entered between 1993 and 2011. Kingston General Hospital and Hotel Dieu Hospital provide the two Kingston, Ontario, sites for emergency department (ED) care and participate in CHIRPP. Each retrieved entry underwent a chart review. A secondary survey was mailed to select individuals who had experienced curling injuries to solicit details on their injury and attitudes towards equipment to prevent injury. We used descriptive statistics for rates and proportions. RESULTS: Over 90% of acute curling injuries resulted from a fall, and 31.7% were head impacts. We found that acute injuries requiring ED presentation occur at a rate of approximately 0.17 per 1000 athlete-exposures (95% CI: 0.12-0.22). The secondary survey was completed by 54% of potential respondents. Of survey respondents, 41.3% attributed their fall to a lack of proper footwear and 73.5% of respondents agreed with mandatory sport-specific footwear as a prevention strategy, but only 8% agreed with mandatory helmet wear. CONCLUSION: Although curling injuries requiring medical care are not common, head injuries make up a large proportion. Mandated use of appropriate footwear appears to be the most effective prevention strategy, as well as the measure deemed most acceptable by players.

TITRE: Les traumatismes crâniens font partie des blessures associées au curling récréatif qui peuvent être évitées en portant des chaussures appropriées. INTRODUCTION: Notre étude s'intéresse à une population de joueurs de curling et vise à décrire la fréquence des blessures, à estimer le risque de se blesser et à évaluer l'opinion des joueurs à l'égard des stratégies de prévention axées sur l'équipement. MÉTHODOLOGIE: Dans le cadre d'une étude de série de cas rétrospective, nous avons fait des recherches dans le Système canadien hospitalier d'information et de recherche en prévention des traumatismes (SCHIRPT), une base de données nationale pour la surveillance des blessures, en vue d'y repérer les blessures subies au curling répertoriées entre 1993 et 2011. L'Hôpital général de Kingston et l'Hôpital Hôtel-Dieu sont les deux hôpitaux de Kingston (Ontario) qui offrent des services d'urgence et qui font partie du réseau du SCHIRPT. Pour chaque entrée trouvée, nous avons procédé à l'analyse du dossier du patient. Un sondage complémentaire a été envoyé à certaines personnes ayant subi des blessures au curling afin d'en connaître les détails et de savoir ce qu'elles pensent du port d'un équipement comme mesure de prévention. Nous avons utilisé des statistiques descriptives pour les taux et les proportions. RÉSULTATS: Plus de 90 % des blessures graves au curling résultent d'une chute et 31,7 % des cas de blessures graves sont constitués de choc à la tête. Nous avons calculé que le taux de blessures graves qui nécessitent une consultation aux services d'urgence est approximativement de 0,17 pour 1 000 athlètes exposés (intervalle de confiance à 95 % : de 0,12 à 0,22). Le sondage complémentaire a été rempli par 54 % des joueurs blessés ciblés. Parmi eux, 41,3 % attribuent leur chute à l'absence de chaussures appropriées. Concernant les stratégies de prévention, 73,5 % des répondants étaient d'accord avec la suggestion du port obligatoire de chaussures spécialisées, mais seulement 8 % avec celle du port obligatoire du casque. CONCLUSION: Bien que les blessures subies au curling qui nécessitent des soins médicaux ne soient pas courantes, les traumatismes crâniens représentent une proportion importante de ces blessures. Le port obligatoire de chaussures appropriées semble constituer la mesure de prévention la plus efficace et la plus acceptable pour les joueurs.

Physician beliefs about the impact of meaningful use of the EHR: a cross-sectional study.

BACKGROUND: As adoption and use of electronic health records (EHRs) grows in the United States, there is a growing need in the field of applied clinical informatics to evaluate physician perceptions and beliefs about the impact of EHRs. The meaningful use of EHR incentive program provides a suitable context to examine physician beliefs about the impact of EHRs. OBJECTIVE: Contribute to the sparse literature on physician beliefs about the impact of EHRs in areas such as quality of care, effectiveness of care, and delivery of care. METHODS: A cross-sectional online survey of physicians at two academic medical centers (AMCs) in the northeast who were preparing to qualify for the meaningful use of EHR incentive program. RESULTS: Of the 1,797 physicians at both AMCs who were preparing to qualify for the incentive program, 967 completed the survey for an overall response rate of 54%. Only 23% and 27% of physicians agreed or strongly agreed that meaningful use of the EHR will help them improve the care they personally deliver and improve quality of care respectively. Physician specialty was significantly associated with beliefs; e.g., 35% of primary care physicians agreed or strongly agreed that meaningful use will improve quality of care compared to 26% of medical specialists and 21% of surgical specialists (p=0.009). Satisfaction with outpatient EHR was also significantly related to all belief items. CONCLUSIONS: Only about a quarter of physicians in our study responded positively that meaningful use of the EHR will improve quality of care and the care they personally provide. These findings are similar to and extend findings from qualitative studies about negative perceptions that physicians hold about the impact of EHRs. Factors outside of the regulatory context, such as physician beliefs, need to be considered in the implementation of the meaningful use of the EHR incentive program.

Pneumodescemetopexy with perfluoroethane (C2F6) for the treatment of acute hydrops secondary to keratoconus.

PURPOSE: To evaluate the efficacy and safety of pneumodescemetopexy with intracameral perfluoroethane (C2F6) gas for the treatment of acute hydrops secondary to keratoconus. METHODS: Retrospective, non-comparative, interventional case series. Eight eyes of eight patients who presented with acute hydrops secondary to keratoconus between July 2009 and September 2013 were consecutively recruited. All were treated with intracameral 14% isoexpansile concentration of C2F6. Preoperative and postoperative best-corrected visual acuities (BCVA), intraoperative and postoperative complications, and time taken for resolution of corneal oedema were assessed. RESULTS: All the patients, except for one, were followed up for 1 year. The mean age of the cohort was 29.1±13.5 years. BCVA at presentation was 6/60 or less in all patients. Improvement of BCVA was achieved postoperatively in seven (87.5%) patients, with three (37.5%) patients achieving a BCVA of 6/18. The average time between initial presentation and complete resolution of corneal oedema was 60.0±32.1 days. The C2F6 gas persisted in the anterior chamber between 6 and 8 days. All the patients required only one injection during the treatment period. There was no intraoperative or postoperative complication noted during the follow-up period. CONCLUSION: Pneumodescemetopexy with intracameral isoexpansile concentration of C2F6 gas serves as a safe and effective treatment modality for patients with acute hydrops secondary to keratoconus.

Retinal video recordings at different compression levels: a novel video-based imaging technology for diabetic retinopathy screening.

BACKGROUND: To evaluate the optimal compression level of retinal color digital video recordings, a novel video-based imaging technology, in screening for diabetic retinopathy (DR). DESIGN: Evaluation of a diagnostic technique. METHODS: A total of 36 retinal videos, captured using EyeScan (Ophthalmic Imaging System), were compressed from original uncompressed file size of 1 GB (gigabyte) to four different compression levels-100 MB (megabyte) (Group 1); 30 MB (Group 2); 20 MB (Group 3); and 5 MB (Group 4). The videos were subsequently interpreted by an ophthalmologist and a resident using the International Clinical Diabetic Retinopathy Severity Scales. MAIN OUTCOME MEASURES: The sensitivity, specificity and κ coefficient for DR grading detected by were calculated for each compression level (Groups 1-4), with reference to the original uncompressed retinal videos. RESULTS: Groups 1, 2, and 3 graded by both readers had sensitivity and specificity >90% in detecting DR, whereas for group 4, the sensitivity and specificity were 70.6% and 94.7% for ophthalmologist and 80.0% and 72.2% medical officer, respectively. The κ correlation in detecting DR for groups 1, 2, and 3 were >0.95, whereas for Group 4, the κ was 0.76 and 0.66 for ophthalmologist and medical officer, respectively. CONCLUSION: Retinal video recording is a novel and effective DR screening technique with high sensitivity, specificity and κ correlation. With its compressibility, this is a potential effective technique that can be widely implemented in a routine, mobile, and tele-ophthalmology setting for DR screening services.

Implantation of a customized toric intraocular lens for correction of post-keratoplasty astigmatism.

PURPOSE: To report visual and refractive outcomes, and endothelial cell loss following primary and secondary 'piggyback' toric intraocular lens (IOL) implantation in patients with high post-penetrating keratoplasty (PK) astigmatism. METHODS: Prospective case series. Nine eyes of nine patients with post-PK astigmatism were consecutively recruited for implantation of a customized toric IOL. Six underwent simultaneous phacoemulsification (PE) and three pseudophakic eyes had a secondary 'piggyback' toric IOL implanted in the ciliary sulcus. Mean follow-up time was 17.2±7.7 months. Pre- and post-operative uncorrected (UDVA) and best-corrected (BDVA) distance visual acuities and refractive errors were collected for comparison. Cartesian astigmatic vectors were calculated to identify a change in the magnitude of astigmatism pre- compared to postoperatively. Pre- and post-operative endothelial cell counts were also collected for analysis. RESULTS: UDVA (logMAR) improved from 1.13±0.51 preoperatively to 0.48±0.24 postoperatively (P-value=0.003). There was no significant change in BDVA (P-value=0.905) from 0.31±0.27 to 0.26±0.19. Corneal astigmatism preoperatively was 6.57±4.40 diopters (D). Post-operative refractive cylinder was 0.83±1.09 D compared to 3.89±4.01 D preoperatively (P=0.039). Analysis of astigmatic Cartesian x and y coordinates found a significant reduction postoperatively compared to preoperatively (P=0.005 and P=0.002), respectively. Mean endothelial cell loss was 9.9%. CONCLUSION: Implantation of a customized primary or secondary 'piggyback' toric IOL serves as an effective modality in treating patients with high post-PK astigmatism.

Diabetic retinopathy screening: can the viewing monitor influence the reading and grading outcomes.

PURPOSE: To evaluate the accuracy of different viewing monitors for image reading and grading of diabetic retinopathy (DR). DESIGN: Single-centre, experimental case series-evaluation of reading devices for DR screening. METHOD: A total of 100 sets of three-field (optic disc, macula, and temporal views) colour retinal still images (50 normal and 50 with DR) captured by FF 450 plus (Carl Zeiss) were interpreted on 27-inch iMac, 15-inch MacBook Pro, and 9.7-inch iPad. All images were interpreted by a retinal specialist and a medical officer. We calculated the sensitivity and specificity of 15-inch MacBook Pro and 9.7-inch iPad in detection of DR signs and grades with reference to the reading outcomes obtained using a 27-inch iMac reading monitor. RESULTS: In detection of any grade of DR, the 15-inch MacBook Pro had sensitivity and specificity of 96% (95% confidence interval (CI): 85.1-99.3) and 96% (95% CI: 85.1-99.3), respectively, for retinal specialist and 91.5% (95% CI: 78.7-97.2) and 94.3% (95% CI: 83.3-98.5), respectively, for medical officer, whereas for 9.7-inch iPad, they were 91.8% (95% CI: 79.5-97.4) and 94.1% (95% CI: 82.8-98.5), respectively, for retinal specialist and 91.3% (95% CI: 78.3-97.1) and 92.6% (95% CI: 81.3-97.6), respectively, for medical officer. CONCLUSION: The 15-inch MacBook Pro and 9.7-inch iPad had excellent sensitivity and specificity in detecting DR and hence, both screen sizes can be utilized to effectively interpret colour retinal still images for DR remotely in a routine, mobile or tele-ophthalmology setting. Future studies could explore the use of more economical devices with smaller viewing resolutions to reduce cost implementation of DR screening services.

Bone transport osteogenesis for treatment of canine osteomyelitis. A report of two cases.

Bone transport osteogenesis, as described by Ilizarov, has been used to resolve segmental bone defects in both human and veterinary patients. These defects are created when a large osseous tumour, sequestrum, or non-union fracture is resected. This report documents two cases in which the principle of bone transport osteogenesis was applied by utilising the Ilizarov technique to bridge large osseous defects resulting from debridement of an infected nonunion fracture (case 1) and debridement of a sequestrum (case 2). Defects were treated by transporting either a complete or a hemi-circumferential bone segment. Both cases had resolution of osteomyelitis, satisfactory fracture union, and functional usage of the limb 39 weeks and 15 weeks post-surgery, respectively. Although manageable complications were encountered during the treatment of these cases, the long-term clinical outcome was eventually favorable. The authors believe that bone transport osteogenesis offers a valid restorative option in the treatment of bone defects resulting from extensive debridement and seque- strectomy.

Effect of bending direction on the mechanical behaviour of interlocking nail systems.

OBJECTIVES: To compare the mechanical properties of various interlocking nail constructs in medio-lateral (ML) and cranio-caudal (CC) bending. METHODS: Synthetic bone models simulating a severely comminuted tibial fracture were treated with either screwed or bolted, 6 or 8 mm standard interlocking nails (ILN), or an angle-stable ILN (AS-ILN), after which they were then sequentially tested in ML and CC bending. Construct compliance, maximum angular deformation (MaxDef) and slack were statistically compared (p<0.05). RESULTS: The compliance of all constructs was significantly greater in CC than in ML bending. However, due to the presence of a greater slack in the ML plane, standard ILN constructs sustained significantly more deformation in that plane. Maximum deformation of the novel AS-ILN constructs was the smallest of all constructs and consistently occurred without slack regardless of bending direction. CLINICAL SIGNIFICANCE: This study suggested that standard ILN construct overall deformation and acute instability (slack) may be more critical in ML than in CC bending. Conversely, the small MaxDef and the absence of slack in both bending planes seen in novel angle-stable AS-ILN may provide optimal construct stability and in turn may be more conducive to bone healing.

The nuclear membrane organization of leukotriene synthesis.

Leukotrienes (LTs) are signaling molecules derived from arachidonic acid that initiate and amplify innate and adaptive immunity. In turn, how their synthesis is organized on the nuclear envelope of myeloid cells in response to extracellular signals is not understood. We define the supramolecular architecture of LT synthesis by identifying the activation-dependent assembly of novel multiprotein complexes on the outer and inner nuclear membranes of mast cells. These complexes are centered on the integral membrane protein 5-Lipoxygenase-Activating Protein, which we identify as a scaffold protein for 5-Lipoxygenase, the initial enzyme of LT synthesis. We also identify these complexes in mouse neutrophils isolated from inflamed joints. Our studies reveal the macromolecular organization of LT synthesis.