Search

Abstract Introduction The phase 3, randomized, vehicle-controlled, 14-day VIRGO study evaluated the efficacy and safety of twice-daily dosing of pilocarpine hydrochloride ophthalmic solution 1.25% (Pilo) in presbyopia. On VIRGO exit, a companion study was conducted to assess the patient experience with presbyopia and satisfaction with Pilo. Methods Recruited individuals completed the Presbyopia Patient Satisfaction Questionnaire (PPSQ) plus a three-part exit survey, or a live interview. The PPSQ evaluated respondents’ experience with Pilo. Survey parts 1 and 2 evaluated experience managing presbyopia before and during VIRGO, respectively; part 3 assessed future possibilities of using Pilo in real-world situations. The interview further informed the interviewees’ experience with presbyopia and Pilo. The primary endpoint was responders (%) in each rating category of the PPSQ items 1–7; the secondary endpoints were summary of categorical (survey) and qualitative (interviews) responses. Results The PPSQ and survey included 62 participants who received Pilo (N = 28) or vehicle (N = 34) in VIRGO; the interview included ten participants (Pilo, N = 4; vehicle, N = 6). Per the PPSQ, 64.3% of Pilo users reported vision improvement, including 17.9% with complete improvement; ≥ 46.4% were satisfied/very satisfied with their ability to perform daily activities, see up close unaided, and read in dim light. Among vehicle users, these percentages were 35.3%, 0%, and ≤ 23.5%, respectively. In both subgroups, ≥ 67.9% were interested in using Pilo or Pilo and eyeglasses/contact lenses in the future. Per the interview, vehicle users (n = 6/6) found the eyedrop easy to use but none experienced meaningful near-vision improvements, stopped using other correction method(s) part of the day, were satisfied with the eyedrop, preferred it over their previous correction method(s), or would continue using it if prescribed. Conversely, 75% (n = 3/4) of Pilo users responded positively to each of these six criteria. Conclusions Findings validate the VIRGO results and improve our understanding of the patient experience, demonstrating improved vision and satisfaction with Pilo (vs. vehicle) when performing daily activities.

Firefighters are exposed to dangerous and often traumatic events due to the nature of their occupational demands. This repeated exposure to trauma combined with stressful work demands increases their risk for negative physiological and psychological health outcomes. The high prevalence of adverse health outcomes highlights the need for interventions to improve resiliency in firefighters. Resiliency is the ability to reduce the effect of crisis, rebound from adversity, and recover to pre-stimulus homeostasis. When traumatic exposures are unavoidable, as is the case with firefighters, it is important to buffer the resulting consequences on health. While resilience has a genetic component, interventions targeting physiological, psychological, and social components have been successful at improving resilience. These factors are of specific interest as increases in resilience have been linked to improved PTSD symptomology/severity, depression, anxiety, autonomic nervous system activation, hypothalamus–pituitary axis balance, and brain-derived neurotrophic factor. Therefore, the purpose of this review is to identify physiological and psychological components associated with resiliency and discuss strategies that may improve those components to ultimately increase resiliency in firefighters. The strategies discussed include exercise, social support, and mindfulness.

Abstract Background Growth factors, such as EGF, activate the PI3K/Akt/mTORC1 signalling pathway, which regulates a distinct program of protein synthesis leading to cell growth. This pathway relies on mTORC1 sensing sufficient levels of intracellular amino acids, such as leucine, which are required for mTORC1 activation. However, it is currently unknown whether there is a direct link between these external growth signals and intracellular amino acid levels. In primary prostate cancer cells, intracellular leucine levels are regulated by L-type amino acid transporter 3 (LAT3/SLC43A1), and we therefore investigated whether LAT3 is regulated by growth factor signalling. Methods To investigate how PI3K/Akt signalling regulates leucine transport, prostate cancer cells were treated with different PI3K/Akt inhibitors, or stable knock down of LAT3 by shRNA, followed by analysis of leucine uptake, western blotting, immunofluorescent staining and proximity ligation assay. Results Inhibition of PI3K/Akt signalling significantly reduced leucine transport in LNCaP and PC-3 human prostate cancer cell lines, while growth factor addition significantly increased leucine uptake. These effects appeared to be mediated by LAT3 transport, as LAT3 knockdown blocked leucine uptake, and was not rescued by growth factor activation or further inhibited by signalling pathway inhibition. We further demonstrated that EGF significantly increased LAT3 protein levels when Akt was phosphorylated, and that Akt and LAT3 co-localised on the plasma membrane in EGF-activated LNCaP cells. These effects were likely due to stabilisation of LAT3 protein levels on the plasma membrane, with EGF treatment preventing ubiquitin-mediated LAT3 degradation. Conclusion Growth factor-activated PI3K/Akt signalling pathway regulates leucine transport through LAT3 in prostate cancer cell lines. These data support a direct link between growth factor and amino acid uptake, providing a mechanism by which the cells rapidly coordinate amino acid uptake for cell growth.

Introduction: This study examined acceptance by staff and patients of a therapy dog (TD) in the emergency department (ED).Methods: Immediately after TD visits to a University Hospital ED, all available ED staff, patients, and their visitors were invited to complete a survey.Results: Of 125 ‘‘patient’’ and 105 staff responses, most were favorable. Ninety-three percent of patients and 95% of staff agreed that TDs should visit EDs; 87.8% of patients and 92% of staff approved of TDs for both adult and pediatric patients. Fewer than 5% of either patients or staff were afraid of the TDs. Fewer than 10% of patients and staff thought the TDs posed a sanitary risk or interfered with staff work.Conclusion: Both patients and staff approve of TDs in an ED. The benefits of animal-assisted therapy should be further explored in the ED setting.

Acute ethanol administration is associated with sedation and analgesia as well as behavioral disinhibition and memory loss but the mechanisms underlying these effects remain to be elucidated. During the past decade, insects have emerged as important model systems to understand the neural and genetic bases of alcohol effects. However, novel assays to assess ethanol's effects on complex behaviors in social or isolated contexts are necessary. Here we used the honey bee as an especially relevant model system since bees are typically exposed to ethanol in nature when collecting standing nectar crop of flowers, and there is recent evidence for independent biological significance of this exposure for social behavior. Bee's inhibitory control of the sting extension response (SER) and a conditioned-place aversion assay were used to study ethanol effects on analgesia, behavioral disinhibition, and associative learning. Our findings indicate that although ethanol, in a dose-dependent manner, increases SER thresholds (analgesic effects), it disrupts the ability of honey bees to inhibit SER and to associate aversive stimuli with their environment. These results suggest that ethanol's effects on analgesia, behavioral disinhibition and associative learning are common across vertebrates and invertebrates. These results add to the use of honey bees as an ethanol model to understand ethanol's effects on complex, socially relevant behaviors.

BackgroundQuality measures provide a way to assess health care delivery and to identify areas for improvement that can inform patient care delivery. When operationalized by a hospital or a payer, quality measures can also be tied to physician or hospital reimbursement. Prior work on quality measures in orthopaedic surgery have identified substantial gaps in measurement portfolios and have highlighted areas for future measure development. This study aims to identify the portfolio of quality measures in pediatric orthopaedic surgery.MethodsWe used methodology of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and reviewed PubMed/ MEDLINE and EMBASE, the American Academy of Orthopaedic Surgery (AAOS), National Quality Forum (NQF), and the Agency for Healthcare Research and Quality (AHRQ), for quality measures and candidate quality measures. Quality measure and candidate quality measures were categorized as structure, process, or outcome. Measures were also classified into 1 of the 6 National Quality Strategy priorities (safety, effective, patient centered, timely, efficient, and equitable).ResultsA review of PubMed/EMBASE returned 1640 potential quality measures and articles. A review of AAOS, NQF, and AHRQ databases found 80 potential quality measures. After screening we found a total of 18 quality measures and candidate quality measures specifically for pediatric orthopaedic surgery. Quality measures addressed conditions such as supracondylar humerus fractures, developmental dysplasia of the hip, and osteochondritis dissecans. There were 10 process measures, 8 outcome measure, and 0 structure measures. When we categorized by National Quality Strategy priorities and found 50% (9/18) were effective clinical care, 44% (8/18) were person and care-giver centered experience and outcomes, 6% (1/18) were efficient use of resources.ConclusionsThere are few quality measures and candidate quality measures to assess pediatric orthopaedic surgery. Of the quality measure available, process measures are relatively over-represented. Pediatric orthopaedic surgeons can lead the development of outcome (eg, patient-reported outcomes after surgery) and structure measures (eg, subspecialty training certification) to assess quality of care in pediatric orthopaedic surgery.Level of evidenceLevel II-systematic review.

Quantification of neuromotor symptoms with device-based measures provides a useful supplement to clinical evaluation. Research using the CATSYS has established its utility as a computerized measurement system to quantify neuromotor function. The primary objective of this study is to provide technical guidance on the use of the CATSYS in Parkinson's disease (PD). Forty-four patients with idiopathic PD and 28 healthy controls were prospectively recruited and evaluated with CATSYS, a portable, Windows-based system consisting of a data logger and four different sensors (tremor pen, touch recording plate, reaction time handle, and force plate for balance recording) for quantification of neuromotor functions. CATSYS discriminated between PD and controls on measurements of rest/postural tremor, pronation/supination, finger tapping, simple reaction time, and postural sway intensity and velocity. CATSYS measurements using the proposed test battery were associated with relevant clinician-rated Unified Parkinson's disease rating scale (UPDRS) items assessing tremor and bradykinesia. More work is warranted to establish CATSYS as a diagnostic/monitoring instrument in movement disorders using the proposed technical approaches.

ImportanceIncreased pulse pressure associated with age-related arterial stiffening increases risk for Alzheimer dementia but the mechanism responsible for this association remains unclear.ObjectivesTo determine the relationship between pulse pressure and cerebral spinal fluid biomarker profiles of preclinical Alzheimer disease, investigate whether observed relationships are stronger in adults with more advanced arterial age (≥80 years of age), and examine the relationship between pulse pressure and progression to dementia.Design, setting, and participantsIn this retrospective cohort study, 877 participants without dementia (55-91 years of age) from the Alzheimer's Disease Neuroimaging Initiative underwent baseline health assessment, including blood pressure assessment and lumbar puncture for determination of cerebral spinal fluid phosphorylated tau (P-tau) and β-amyloid 1-42. Participants have been followed up longitudinally since 2005. The last date of examination was October 15, 2013. Clinical follow-up between 6 and 96 months tracked progression to dementia.Main outcomes and measuresRegression and analysis of covariance analyses investigated relationships between pulse pressure and distinct cerebral spinal fluid biomarker profiles. Very old participants (80 years or older) were compared with younger participants (55-79 years of age) on clinical measures and pulse pressure × age group interactions were investigated. Survival analysis examined the effect of baseline pulse pressure on progression to dementia. Covariates were age, sex, apolipoprotein E genotype, body mass index, vascular risk factors, and antihypertensive medication use.ResultsIndividuals with a P-tau-positive biomarker profile exhibited mean (SD) elevated pulse pressure regardless of age (62.0 [15.6] mm Hg for a P-tau-positive biomarker vs 57.4 [14.0] mm Hg for P-tau-negative biomarker; P = .04). In very old participants, a further increase in pulse pressure was observed in those exhibiting both P-tau elevation and β-amyloid 1-42 reduction vs either biomarkers alone (69.7 [16.0] mm Hg for both positive biomarkers vs 63.18 [13.0] mm Hg for P-tau alone vs 60.1 [16.4] mm Hg for β-amyloid 1-42 alone vs 56.6 [14.5] mm Hg for negative biomarkers; P = .003). Those with higher baseline pulse pressure progressed to dementia more rapidly (95% CI, 1.000-1.048; P = .05; hazard ratio = 1.024). Systolic pressure exhibited similar relationships with Alzheimer disease biomarkers and progression to dementia in the very old subgroup (P < .05) but showed no associations in the young old subgroup (P > .10). Diastolic pressure was reduced in young old participants with isolated phosphorylated tau elevation (P = .04).Conclusions and relevancePulse pressure, an index of vascular aging, was associated with neurodegenerative change prior to the onset of dementia across a broad age range. Among those with more advanced age, higher pulse pressure was also associated with cerebral amyloidosis in the presence of neurodegeneration and more rapid progression to dementia. Diastolic contributions to these biomarker associations were limited to young old participants whereas systolic contributions were found only in very old participants.

Atrophy of the hippocampus and surrounding temporal regions occurs in Alzheimer's disease (AD). APOE ε4, the major genetic risk factor for late-onset AD, has been associated with smaller volume in these regions before amyloidosis can be detected by AD biomarkers. To examine APOE ε4 effects in relation to aging, we performed a longitudinal magnetic resonance imaging study involving cognitively normal adults (25 APOE ε4 carriers and 31 ε3 homozygotes), initially aged 51-75 years. We used growth curve analyses, which can provide information about APOE ε4-related differences initially and later in life. Hippocampal volume was the primary outcome; nearby medial temporal regions were secondary outcomes. Brain-derived neurotrophic factor, val66met was a secondary covariate. APOE ε4 carriers had significantly smaller initial hippocampal volumes than ε3 homozygotes. Rate of hippocampal atrophy was not greater in the APOE ε4 group, although age-related atrophy was detected in the overall sample. The findings add to the growing evidence that effects of APOE ε4 on hippocampal size begin early in life, underscoring the importance of early interventions to increase reserve.

BackgroundPrevious research suggests that the size of the hippocampus can vary in response to intensive training (e.g., during the acquisition of expert knowledge). However, the role of the hippocampus in maintenance of skilled performance is not well understood. The Stanford/Veterans Affairs Aviation MRI Study offers a unique opportunity to observe the interaction of brain structure and multiple levels of expertise on longitudinal flight simulator performance.MethodsThe current study examined the relationship between hippocampal volume and three levels of aviation expertise, defined by pilot proficiency ratings issued by the U.S. Federal Aviation Administration (11). At 3 annual time points, 60 pilots who varied in their level of aviation expertise (ages ranging from 45 to 69 yr) were tested.ResultsAt baseline, higher expertise was associated with better flight simulator performance, but not with hippocampal volume. Longitudinally, there was an Expertise x Hippocampal volume interaction, in the direction that a larger hippocampus was associated with better performance at higher levels of expertise.DiscussionThese results are consistent with the notion that expertise in a cognitively demanding domain involves the interplay of acquired knowledge ('mental schemas') and basic hippocampal-dependent processes.

Introduction: This study examined acceptance by staff and patients of a therapy dog (TD) in the emergency department (ED).Methods: Immediately after TD visits to a University Hospital ED, all available ED staff, patients, and their visitors were invited to complete a survey.Results: Of 125 ‘‘patient’’ and 105 staff responses, most were favorable. Ninety-three percent of patients and 95% of staff agreed that TDs should visit EDs; 87.8% of patients and 92% of staff approved of TDs for both adult and pediatric patients. Fewer than 5% of either patients or staff were afraid of the TDs. Fewer than 10% of patients and staff thought the TDs posed a sanitary risk or interfered with staff work.Conclusion: Both patients and staff approve of TDs in an ED. The benefits of animal-assisted therapy should be further explored in the ED setting. [West J Emerg Med. 2012;13(4):363–365.]