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Novel psychoactive substances, including synthetic substituted tryptamines, represent a potential public health threat. Additionally, some substituted tryptamines are being studied under medical guidance as potential treatments of psychiatric disorders. Characterizing the basic pharmacology of substituted tryptamines will aid in understanding differences in potential for harm or therapeutic use. Using human embryonic kidney cells stably expressing 5-hydroxytryptamine (5-HT)1A, 5-HT2A, and 5-HT2C receptors (5-HT1AR, 5-HT2AR, and 5HT2CR, respectively) or the serotonin transporter (SERT), we measured affinities, potencies and efficacies of 21 substituted tryptamines. With the exception of two 4-acetoxy compounds, substituted tryptamines exhibited affinities and potencies less than one micromolar at the 5-HT2AR, the primary target for psychedelic effects. In comparison, half or more exhibited low affinities/potencies at 5-HT2CR, 5-HT1AR, and SERT. Sorting by the ratio of 5-HT2A to 5-HT2C, 5-HT1A, or SERT affinity revealed chemical determinants of selectivity. We found that although 4-substituted compounds exhibited affinities that ranged across a factor of 100, they largely exhibited high selectivity for 5-HT2ARs versus 5-HT1ARs and 5-HT2CRs. 5-substituted compounds exhibited high affinities for 5-HT1ARs, low affinities for 5-HT2CRs, and a range of affinities for 5-HT2ARs, resulting in selectivity for 5-HT2ARs versus 5-HT2CRs but not versus 5-HT1ARs. Additionally, a number of psychedelics bound to SERT, with non-ring-substituted tryptamines most consistently exhibiting binding. Interestingly, substituted tryptamines and known psychedelic standards exhibited a broad range of efficacies, which were lower as a class at 5-HT2ARs compared with 5-HT2CRs and 5-HT1ARs. Conversely, coupling efficiency/amplification ratio was highest at 5-HT2ARs in comparison with 5-HT2CRs and 5-HT1ARs. SIGNIFICANCE STATEMENT: Synthetic substituted tryptamines represent both potential public health threats and potential treatments of psychiatric disorders. The substituted tryptamines tested differed in affinities, potencies, and efficacies at 5-hydroxytryptamine (5-HT)2A, 5-HT2C, and 5HT1A receptors and the serotonin transporter (SERT). Several compounds were highly selective for and coupled very efficiently downstream of 5-HT2A versus 5-HT1A and 5-HT2C receptors, and some bound SERT. This basic pharmacology of substituted tryptamines helps us understand the pharmacologic basis of their potential for harm and as therapeutic agents.
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Alucinógenos , Triptaminas , Humanos , Triptaminas/farmacologia , Serotonina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina , Receptor 5-HT2A de Serotonina/metabolismo , Receptor 5-HT2C de Serotonina/metabolismoRESUMO
Sleep disturbances are common in older adults and may contribute to disease progression in certain populations (e.g., Alzheimer's disease). Light therapy is a simple and cost-effective intervention to improve sleep. Primary barriers to light therapy are: (1) poor acceptability of the use of devices, and (2) inflexibility of current devices to deliver beyond a fixed light spectrum and throughout the entirety of the day. However, dynamic, tunable lighting integrated into the native home lighting system can potentially overcome these limitations. Herein, we describe our protocol to implement a whole-home tunable lighting system installed throughout the homes of healthy older adults already enrolled in an existing study with embedded home assessment platforms (Oregon Center for Aging & Technology-ORCATECH). Within ORCATECH, continuous data on room location, activity, sleep, and general health parameters are collected at a minute-to-minute resolution over years of participation. This single-arm longitudinal protocol collected participants' light usage in addition to ORCATECH outcome measures over a several month period before and after light installation. The protocol was implemented with four subjects living in three ORCATECH homes. Technical/usability challenges and feasibility/acceptability outcomes were explored. The successful implementation of our protocol supports the feasibility of implementing and integrating tunable whole-home lighting systems into an automated home-based assessment platform for continuous data collection of outcome variables, including long-term sleep measures. Challenges and iterative approaches are discussed. This protocol will inform the implementation of future clinical intervention trials using light therapy in patients at risk for developing Alzheimer's disease and related conditions.
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Doença de Alzheimer , Transtornos do Sono-Vigília , Idoso , Coleta de Dados , Estudos de Viabilidade , Humanos , IluminaçãoRESUMO
UNLABELLED: COMPREHENSIVE ADULT MEDICAL EYE EVALUATION® PREFERRED PRACTICE PATTERN® GUIDELINES: Evidence-based update of the Comprehensive Adult Medical Eye Evaluation Preferred Practice Pattern® (PPP) guidelines, discussing the rationale and components of an ophthalmic evaluation for adult patients with and without risk factors.
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Oftalmopatias/terapia , Oftalmologia/normas , Padrões de Prática Médica/normas , Adulto , Gerenciamento Clínico , HumanosRESUMO
BACKGROUND: To evaluate the effect of varying levels of power on phacoemulsification efficiency using the CENTURION Vision System. METHODS: Formalin-soaked porcine lenses were divided into 2-mm cubes; 0.9-mm, balanced tips were used. Torsional power levels were tested from 10% to 100% at 10% intervals. Vacuum was set to 550 mmHg, aspiration to 50 ml/min, and intraocular pressure at 50 mmHg. Efficiency (time to lens removal) and chatter (number of lens fragment repulsions from the tip) were determined. RESULTS: Increasing torsional power up to 60% increased efficiency. This effect was linear from 30 to 60% power (R2 = .90; P < 0.05). There were no significant differences in efficiency past 60%. Chatter was highest at 10% power and decreased linearly (R2 = .87; P = 0.007) as power was increased up to 60% power, and chatter did not improve above this power level. CONCLUSIONS: Power improved efficiency only up to a 60% power level, and then was negligible. Chatter correlated well with power up to the 60% level, so that as power was increased, chatter decreased. Because there are no additional benefits in efficiency past 60% power, and because chatter is minimal at 60% power, we recommend torsional ultrasound at 60% as the optimal power setting for using the CENTURION System for phacoemulsification.l.
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Facoemulsificação/instrumentação , Torção Mecânica , Animais , Catarata/etiologia , Modelos Animais de Doenças , Drenagem/métodos , Pressão Intraocular/fisiologia , Cristalino/cirurgia , Facoemulsificação/métodos , Suínos , VácuoRESUMO
PURPOSE: The purpose of this study was to determine whether there is an increased risk of mortality among individuals with keratoconus. METHODS: This was a retrospective, case-control study using the Utah Population Database. Cases were defined as individuals diagnosed with keratoconus from 1996 to 2020 and were matched 5:1 with controls on birth year, sex, whether born in Utah, and follow-up time in Utah. Individuals diagnosed with trisomy 21 or connective tissue disease were excluded. Main outcome measures were the all-cause and cause-specific mortality among keratoconus cases compared with matched controls. Cox regression models were used, additionally adjusting for race and ethnicity. RESULTS: A total of 7847 keratoconus cases and 38,597 controls were studied in the final analyses. The mean age at index diagnosis was 43 ± 17 years, and mean age at last follow-up was 54 ± 17 years for both cases and controls. At last follow-up, 92% of cases were living compared with 91% of controls. After adjusting for covariates, there were no significant differences in all-cause mortality (P = 0.161), mortality from natural causes (0.222), or mortality from unnatural causes (P = 0.494) between cases and controls. When analyzed according to specific causes of death, keratoconus cases had a higher mortality risk from diseases of the nervous system and sense organs compared with their matching controls (hazard ratio 1.59; 95% confidence interval, 1.19-2.11; P = 0.002). CONCLUSIONS: There was no evidence of an increased risk of mortality among individuals with keratoconus. There may be an increased risk of death due to diseases of the nervous system and sense organs among individuals with keratoconus.
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Working memory (WM) is a critical cognitive function allowing recent information to be temporarily held in mind to inform future action. This process depends on coordination between key subregions in prefrontal cortex (PFC) and other connected brain areas. However, few studies have examined the degree of functional specialization between these subregions throughout the phases of WM using electrophysiological recordings in freely-moving animals, particularly mice. To this end, we recorded single-units in three neighboring medial PFC (mPFC) subregions in mouse - supplementary motor area (MOs), dorsomedial PFC (dmPFC), and ventromedial (vmPFC) - during a freely-behaving non-match-to-position WM task. We found divergent patterns of task-related activity across the phases of WM. The MOs is most active around task phase transitions and encodes the starting sample location most selectively. Dorsomedial PFC contains a more stable population code, including persistent sample-location-specific firing during a five second delay period. Finally, the vmPFC responds most strongly to reward-related information during the choice phase. Our results reveal anatomically and temporally segregated computation of WM task information in mPFC and motivate more precise consideration of the dynamic neural activity required for WM.
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PURPOSE: To explore the efficacy of topical 2.6% EDTA ophthalmic solution (C-KAD) as a treatment to improve visual function for the subgroup of patients with loss of contrast sensitivity (CS) due to early-stage age-related cataract. DESIGN: Subgroup analysis of randomized, double-blinded, placebo-controlled, multicenter phase 1/2 clinical trial data. METHODS: Both eyes of subjects in the intent-to-treat population, with mesopic CS scores between 1 and 7 grating patches (range 0-9, each patch representing 0.15 logCS), at baseline in all five frequencies, were included. The proportion of eyes with clinically significant mesopic CS improvement and mean changes in mesopic CS at spatial frequencies between 1.5 to 18 cycles per degree (cpd), and summary metrics of area under the log CS function (AULCSF), were analyzed. Other exploratory outcomes analyzed included best-corrected visual acuity (BCVA) and lens density for a smaller subgroup of eyes for which Scheimpflug images were available. RESULTS: Forty-one subject eyes were included in the subgroup analysis (C-KAD nâ¯=â¯21, placebo nâ¯=â¯20). The primary endpoint of the proportion of eyes with mesopic CS improvements ≥ 0.30 logCS (equivalent to 100% CS improvement) in at least two of the five spatial frequencies was significantly greater for C-KAD (66.7% versus 35.0% for placebo, Pâ¯=â¯.043) at Day 120. C-KAD met the primary protocol endpoint in this subgroup analysis. The proportion of eyes achieving ≥ 0.30 logCS improvement (mesopic) as measured in AULCSF was also significantly greater for C-KAD, with 42.9% compared to 15.0% for placebo (Pâ¯=â¯.050) at Day 120. The mean change in AULCSF (mesopic) was significantly larger for C-KAD, with 0.25 logCS improvement, versus placebo with 0.06 logCS improvement (Pâ¯=â¯.020) at Day 120. C-KAD also showed significant mesopic CS improvements at spatial frequencies 3 and 6 cpd, with 0.28 logCS (Pâ¯=â¯.004) and 0.31 logCS (Pâ¯=â¯.047) versus placebo at Day 120. Positive BCVA trends and statistical significance in lens density were also observed. CONCLUSIONS: A significant treatment effect of C-KAD in visual function and vision quality was observed consistently. These promising results suggest a novel, non-invasive pharmacological treatment to improve vision in patients with early-stage cataract.
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Administration or consumption of classic psychedelics (CPs) leads to profound changes in experience which are often described as highly novel and meaningful. They have shown substantial promise in treating depressive symptoms and may be therapeutic in other situations. Although research suggests that the therapeutic response is correlated with the intensity of the experience, the neural circuit basis for the alterations in experience caused by CPs requires further study. The medial prefrontal cortex (mPFC), where CPs have been shown to induce rapid, 5-HT2A receptor-dependent structural and neurophysiological changes, is believed to be a key site of action. To investigate the acute neural circuit changes induced by CPs, we recorded single neurons and local field potentials in the mPFC of freely behaving male mice after administration of the 5-HT2A/2C receptor-selective CP, 2,5-Dimethoxy-4-iodoamphetamine (DOI). We segregated recordings into active and rest periods in order to examine cortical activity during desynchronized (active) and synchronized (rest) states. We found that DOI induced a robust decrease in low frequency power when animals were at rest, attenuating the usual synchronization that occurs during less active behavioral states. DOI also increased broadband gamma power and suppressed activity in fast-spiking neurons in both active and rest periods. Together, these results suggest that the CP DOI induces persistent desynchronization in mPFC, including during rest when mPFC typically exhibits more synchronized activity. This shift in cortical dynamics may in part underlie the longer-lasting effects of CPs on plasticity, and may be critical to their therapeutic properties.
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Anfetaminas , Alucinógenos , Córtex Pré-Frontal , Animais , Masculino , Alucinógenos/farmacologia , Alucinógenos/administração & dosagem , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/fisiologia , Camundongos , Anfetaminas/farmacologia , Anfetaminas/administração & dosagem , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Camundongos Endogâmicos C57BL , Comportamento Animal/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologiaRESUMO
PURPOSE: To assess the accuracy of intraocular lens (IOL) power calculation in different age groups using various IOL calculation formulas. METHODS: Data from 421 eyes of 421 patients ≥60 years old (ages: 60-69, n = 131; 70-74, n = 105; 75-84, n = 158 and ≥85, n = 27), who underwent uneventful cataract surgery with SN60WF IOL implantation at John A. Moran Eye Center, Salt Lake City, USA, were retrospectively obtained. The SD of the prediction error (PE), median and mean absolute PEs and the percentage of eyes within ±0.25, ±0.50, ±0.75 and ±1.00 D were calculated after constant optimizations for the following formulas: Barrett Universal II (BUII), Emmetropia Verifying Optical (EVO) 2.0, Haigis, Hoffer Q, Hoffer QST, Holladay 1, Kane, Radial Basis Function (RBF) 3.0 and SRK/T. Results were compared between the different age groups. RESULTS: Predictability rates within 0.25D were lower for the eldest age group compared with the other groups using the EVO 2.0 (33% vs. 37%-53%, p = 0.045), Kane (26% vs. 35%-50%, p = 0.034) and SRK/T (22% vs. 31%-49%, p = 0.002). Higher median absolute refractive errors for all formulas were observed in the oldest group [range: 0.39 D (Haigis, Hoffer QSR)-0.48 D (Kane)], followed by the youngest group [range: 0.30 D (RBF 3.0)-0.39 D (Holladay 1, SRK/T)] but did not reach statistical significance. No significant differences between the groups in the distribution parameter were seen. CONCLUSION: Current IOL power calculation formulas may have variable accuracy for different age groups. This should be taken into account when planning cataract surgery to improve refractive outcomes.
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Biometria , Lentes Intraoculares , Óptica e Fotônica , Refração Ocular , Acuidade Visual , Humanos , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Refração Ocular/fisiologia , Feminino , Masculino , Biometria/métodos , Acuidade Visual/fisiologia , Fatores Etários , Implante de Lente Intraocular/métodos , Facoemulsificação/métodos , Reprodutibilidade dos TestesRESUMO
Psilocybin has been shown to improve symptoms of depression and anxiety when combined with psychotherapy or other clinician-guided interventions. To understand the neural basis for this pattern of clinical efficacy, experimental and conceptual approaches that are different than traditional laboratory models of anxiety and depression are needed. A potential novel mechanism is that acute psilocybin improves cognitive flexibility, which then enhances the impact of clinician-assisted interventions. Consistent with this idea, we find that acute psilocybin robustly improves cognitive flexibility in male and female rats using a task where animals switched between previously learned strategies in response to uncued changes in the environment. Psilocybin did not influence Pavlovian reversal learning, suggesting that its cognitive effects are selective to enhanced switching between previously learned behavioral strategies. The serotonin (5HT) 2A receptor antagonist ketanserin blocked psilocybin's effect on set-shifting, while a 5HT2C-selective antagonist did not. Ketanserin alone also improved set-shifting performance, suggesting a complex relationship between psilocybin's pharmacology and its impact on flexibility. Further, the psychedelic drug 2,5-Dimethoxy-4-iodoamphetamine (DOI) impaired cognitive flexibility in the same task, suggesting that this effect of psilocybin does not generalize to all other serotonergic psychedelics. We conclude that the acute impact of psilocybin on cognitive flexibility provides a useful behavioral model to investigate its neuronal effects relevant to its positive clinical outcome.
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Psilocybin has been shown to improve symptoms of depression and anxiety when combined with psychotherapy or other clinician-guided interventions. To understand the neural basis for this pattern of clinical efficacy, experimental and conceptual approaches that are different than traditional laboratory models of anxiety and depression are needed. A potential novel mechanism is that acute psilocybin improves cognitive flexibility, which then enhances the impact of clinician-assisted interventions. Consistent with this idea, we find that acute psilocybin robustly improves cognitive flexibility in male and female rats using a task where animals switched between previously learned strategies in response to uncued changes in the environment. Psilocybin did not influence Pavlovian reversal learning, suggesting that its cognitive effects are selective to enhanced switching between previously learned behavioral strategies. The serotonin (5HT) 2 A receptor antagonist ketanserin blocked psilocybin's effect on set-shifting, while a 5HT2C-selective antagonist did not. Ketanserin alone also improved set-shifting performance, suggesting a complex relationship between psilocybin's pharmacology and its impact on flexibility. Further, the psychedelic drug 2,5-Dimethoxy-4-iodoamphetamine (DOI) impaired cognitive flexibility in the same task, suggesting that this effect of psilocybin does not generalize to all other serotonergic psychedelics. We conclude that the acute impact of psilocybin on cognitive flexibility provides a useful behavioral model to investigate its neuronal effects relevant to its positive clinical outcome.
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Alucinógenos , Psilocibina , Masculino , Feminino , Animais , Ratos , Psilocibina/farmacologia , Psilocibina/uso terapêutico , Ketanserina/farmacologia , Alucinógenos/farmacologia , Ansiedade , Antagonistas do Receptor 5-HT2 de Serotonina , Serotonina , CogniçãoRESUMO
Purpose: To evaluate efficiency of grooving, nuclear fragment removal, and changes in pressure control in the Oertli Faros using traditional peristaltic and Speed and Precision (SPEEP) features. The SPEEP mode uses novel peristaltic technology permitting independent control of flow and vacuum. Methods: A porcine lens model was used with an enclosed chamber simulating the anterior segment. Grooving efficiency is evaluated with flow rates of 10, 30, and 50 mL/min using whole lenses. Lens cubes were emulsified at 20, 40, 60, 80, and 100% power with both SPEEP and non-SPEEP modes. Surge was evaluated with pressure gauges placed on the irrigation tubing and aspiration tubing. Pressure readings were recorded per the following: fluid and vacuum were initiated for 15 seconds, vacuum tubing was occluded for 5 seconds, tubing patency was then re-introduced for 15 seconds. Differences between sensors were recorded. Results: No significant increase in efficiency was seen with increasing flow rate from 30 to 50 mL/min using SPEEP. No significant differences were shown in lens fragment removal in SPEEP and non-SPEEP modes at any power tested. Pressure difference measurements were not significantly different with SPEEP and non-SPEEP modes. Conclusion: We showed that lower flow rates show comparable efficiency of grooving when using the SPEEP mode. The SPEEP function did not show increased efficiency in nuclear fragment removal when compared to traditional mode. Surge control was also comparable with both SPEEP and non-SPEEP modes. We suggest that the SPEEP function included in the Oertli Faros may have some advantages.
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PURPOSE: To determine whether there is a difference in efficiency during phacoemulsification when using the hybrid polymer tip compared with the metal balanced tip, as measured by cumulative dissipated energy (CDE) and total procedure time. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah. DESIGN: Experimental study. METHODS: Phacoemulsification was performed with the Centurion Vision System and Infiniti OZil handpiece, with a 30-degree bevel metal balanced tip and hybrid polymer tip. The vacuum was set at 500 mm Hg and the aspiration flow rate at 50 mL/min. Power was changed for torsional and longitudinal ultrasound (US) at 20%, 40%, 60%, 80%, and 100%. Hardened porcine lenses were cut into 200 two mm cubes, 10 for each specified tip/power setting. They were placed into an artificial anterior chamber filled with a balanced salt solution, and phacoemulsification was performed. A second observer randomly assigned the US type and power. The same observer timed trials with a stopwatch, and CDE was recorded. RESULTS: There were no significant differences in time or CDE for any power levels or US modes when comparing the 2 tips. CONCLUSIONS: No significant difference in efficiency was observed when comparing the metal balanced tip with the hybrid polymer tip. Given the known improved safety profile and the overall equivalent efficiency of the hybrid tip, it could improve the performance of beginning and advanced surgeons in the future. Future study is needed to evaluate other setting combinations and to evaluate the hybrid tip in clinical settings.
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Purpose: To determine the difference, if any, in grooving efficiency at various settings on the Whitestar Signature Pro phacoemulsification (phaco) system. Methods: Cataractous lenses were simulated by exposing porcine lenses to formalin for 2 hours. A total of 120 lenses were analyzed at various power settings on both longitudinal and transversal handpieces. Twenty trials each were performed with power set to 25%, 50%, and 75% on both handpieces. A Whitestar Phaco Handpiece System was used to provide longitudinal power, and a Whitestar Signature Ellipsis Handpiece provided transversal power. Lenses were placed within a plastic chamber and grooved by an investigator blinded to settings. A second investigator recorded times and adjusted settings. The Whitestar Signature Pro phaco system was used for grooving. Results: There was no significant difference in grooving times between the longitudinal and transverse handpieces at any power setting (P > 0.05). There was a significant decrease in grooving times when comparing the 25% power setting with the 75% power setting for the transversal handpiece (P=0.021). Conclusion: Both longitudinal and transversal handpieces on the Whitestar Signature Pro phaco system produce similar results to one another at each power setting. There is a general trend toward shorter grooving times, reflecting greater efficiency, at higher power settings. Grooving efficiency on the transversal handpiece may be more affected by changes in the power settings as compared with the longitudinal settings.
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Purpose: To understand the role of ophthalmic viscosurgical devices (OVDs) in corneal incision contracture (CIC). Specifically, the aim was to evaluate with the tip of the phacoemulsification needle free of OVD, how various OVDs near the tip and sleeve may transmit thermal energy to the incision site. Methods: A small chamber was filled with balanced saline solution (BSS), and a thin membrane was placed on the surface. OVD was placed atop the membrane. A temperature probe was placed in the OVD, while the handpiece pierced the membrane. The experiment was run both with and without flow and vacuum. Temperature measurements were gathered for each of the OVDs at four separate time points at 0 and 20mL/min flow. Results: As expected, there was a more pronounced temperature increase in all test groups with no fluid flow. While the temperature increase was not significantly different from BSS for any of the OVDs tested at either 0 or 20mL/min, Viscoat showed the most variable results at both flow settings. Conclusion: As long as the phaco tip is not in OVD, residual OVD near the incision is not exothermic and so not an additional risk for CIC.
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OBJECTIVE: To study the thermal properties and response magnitude of a forced-infusion phacoemulsification machine on 4 ophthalmic viscosurgical devices (OVDs). DESIGN: Experimental study. METHODS: A phacoemulsification tip, thermocouple, and gauge were placed into an artificial anterior chamber with balanced saline solution (BSS) or approximately 0.1 mL of OVD. Once the thermocouple measured a consistent temperature, the pedal was engaged for 60 seconds; then the tip was removed. The machine was cooled for 5 minutes and flushed with BSS to return to baseline. This was repeated 10 times for each OVD. The research consisted of 2 scenarios: vacuum-blocked flow rate and low aspiration flow rate. RESULTS: All OVDs showed greater temperature changes than BSS. In the vacuum-blocked scenario, these increases were statistically significant. The medium viscosity dispersive OVD (DiscoVisc) reached temperatures exceeding 60°C. In the low-flow scenario, HEALON5 and DisCoVisc were significantly different at 5 seconds and only HEALON5 at 10 seconds. No temperature increases over BSS were greater than 1.0°C. CONCLUSIONS: The dispersive, cohesive, and viscoadaptive OVDs demonstrated higher temperature changes than BSS but did not reach the threshold for corneal incision contracture. The study team verified the need for at least a minimal flow rate before ultrasound, which is especially evident in the first 10 seconds, because a flow rate of only 20 mL/minute mitigated OVD-related thermal effects. Understanding thermal responses enables corneal incision contracture risk reduction.
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Contratura , Facoemulsificação , Humanos , Combinação de Medicamentos , Sulfatos de Condroitina , Ácido HialurônicoRESUMO
In mammals, sleep duration is highest in the early postnatal period of life and is critical for shaping neural circuits that control the development of complex behaviors. The prairie vole is a wild, highly social rodent that serves as a unique model for the study of complex, species-typical social behaviors. Previous work in our laboratory has found that early life sleep disruption (ELSD) in prairie voles during a sensitive window of postnatal development leads to long lasting changes in social and cognitive behaviors as well as structural changes in excitatory and inhibitory neural circuits in the brain. However, it is currently unknown how later sleep is impacted by ELSD, both shortly after ELSD and over the long term. Therefore, the aim of this study was to describe the effects of ELSD on later life sleep, compared to sleep in normally developing prairie voles. First, we conducted tethered electroencephalogram/electromyogram (EEG/EMG) recordings in juvenile prairie voles undergoing ELSD, compared to Control conditions. Second, we conducted 24 h of home cage tethered EEG/EMG recordings in either adolescent or adult male and female prairie voles that had previously undergone ELSD or Control conditions as juveniles. We found that, as adults, male ELSD prairie voles showed persistently lower REM sleep duration and female ELSD prairie voles showed persistently higher NREM sleep duration compared to Controls, but no other sleep parameters differed. We concluded that 1) persistent effects of ELSD on sleep into adulthood may contribute to the social and cognitive deficits observed in adult voles, and 2) sleep disruption early in life can influence later sleep patterns in adulthood.
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Purpose: To determine the actual vacuum pressure generated by the Oertli CataRhex 3® (Oertli), using an external measuring system. Methods: The effective vacuum pressure created by the Oertli was measured with a pressure device that was continuous with the vacuum tubing system while closed to the external environment. Measurements were taken with the machine set to 300 and 500 mmHg at flow rates of 20, 35, and 50 mL/min and at bottle heights of 60, 80, and 100 cm. Pressures were recorded after the foot pedal was depressed to vacuum setting (second position), and the pressure was allowed to stabilize. Subsequently, it was compared to the pressure value displayed by the machine. Results: Externally measured vacuum pressure was on average 13.02% greater (39.05 mmHg) than displayed vacuum pressure at 300 mmHg (P < 0.005) and 8.60% greater (42.98 mmHg) than displayed vacuum at 500 mmHg (P < 0.005). The average difference between displayed and measured pressure increased with increasing bottle heights. Conclusion: On average, the vacuum pressure generated in the Oertli was found to be significantly higher than the machine's reading when the machine was set at 300 mmHg and 500 mmHg. Adjusting vacuum had variable effects on the measured versus displayed pressure readings.
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PURPOSE: To compare corneal endothelial damage from longitudinal and torsional ultrasound during phacoemulsification. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: 9 New Zealand white rabbits underwent bilateral surgery. After incision, the Intrepid Balanced Tip of the Centurion Ozil handpiece was inserted into the anterior chamber, and the following settings were used: 50 mL/min flow, 70 mm Hg intraocular pressure, 600 mm Hg vacuum, and 60% longitudinal (1 eye) or torsional (contralateral eye) ultrasound for 30 seconds. Cumulative dissipated energy (CDE) was noted. After euthanasia and enucleation, the corneas were removed, stained with trypan blue/alizarin red, and photographed (400× photographs from 5 specific areas and 1 overview photograph from each corneal button). The ImageJ program was used to evaluate cell damage and loss in the photographs obtained from each cornea. RESULTS: Cavitation bubbles around the phacoemulsification tip were generally observed in the longitudinal group. CDE was 17.4 ± 0.58 and 6.93 ± 0.15 in the longitudinal and torsional groups, respectively (P = .003). The percentage of intact cells was statistically higher in the torsional group (94.22% ± 5.99% vs 56.85% ± 22.29%), and the percentage of lost cells was statistically higher in the longitudinal group (42.10% ± 22.02% vs 4.97% ± 6.23%) (P = .003). This was observed in the analysis of the 400× photographs and the overview photographs. CONCLUSIONS: This study suggests that torsional ultrasound was associated with significantly less corneal endothelial cell damage than classical longitudinal tip motion, providing further insight on mechanisms of corneal endothelial damage during phacoemulsification.