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1.
J Pharmacol Exp Ther ; 385(1): 62-75, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36669875

RESUMEN

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.


Asunto(s)
Alucinógenos , Triptaminas , Humanos , Triptaminas/farmacología , Serotonina/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Receptor de Serotonina 5-HT2A/metabolismo , Receptor de Serotonina 5-HT2C/metabolismo
2.
Sensors (Basel) ; 22(14)2022 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-35891052

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer , Trastornos del Sueño-Vigilia , Anciano , Recolección de Datos , Estudios de Factibilidad , Humanos , Iluminación
3.
Ophthalmology ; 123(1): P209-36, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26581558

RESUMEN

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.


Asunto(s)
Oftalmopatías/terapia , Oftalmología/normas , Pautas de la Práctica en Medicina/normas , Adulto , Manejo de la Enfermedad , Humanos
4.
Clin Exp Ophthalmol ; 44(8): 710-713, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26999336

RESUMEN

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.


Asunto(s)
Facoemulsificación/instrumentación , Torsión Mecánica , Animales , Catarata/etiología , Modelos Animales de Enfermedad , Drenaje/métodos , Presión Intraocular/fisiología , Cristalino/cirugía , Facoemulsificación/métodos , Porcinos , Vacio
5.
Cornea ; 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38692671

RESUMEN

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.

6.
Commun Biol ; 7(1): 1235, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39354065

RESUMEN

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 prefrontal cortex (PFC) subregions and other connected brain areas. However, few studies have examined the degree of functional specialization between these subregions throughout WM using electrophysiological recordings in freely-moving mice. Here we record single-units in three neighboring mouse medial PFC (mPFC) subregions-supplementary motor area (MOs), dorsomedial PFC (dmPFC), and ventromedial (vmPFC)-during a freely-behaving non-match-to-position WM task. The MOs is most active around task phase transitions, when it transiently represents the starting sample location. Dorsomedial PFC contains a stable population code, including persistent sample-location-specific firing during the delay period. Ventromedial PFC responds most strongly to reward-related information during choices. Our results reveal subregionally segregated WM computation in mPFC and motivate more precise consideration of the dynamic neural activity required for WM.


Asunto(s)
Memoria a Corto Plazo , Ratones Endogámicos C57BL , Corteza Prefrontal , Animales , Corteza Prefrontal/fisiología , Memoria a Corto Plazo/fisiología , Ratones , Masculino , Recompensa , Neuronas/fisiología
7.
bioRxiv ; 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38712304

RESUMEN

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.

8.
Am J Ophthalmol ; 268: 155-164, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39098755

RESUMEN

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 n = 21, placebo n = 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% vs. 35.0% for placebo, P = .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 (P = .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 (P = .020) at Day 120. C-KAD also showed significant mesopic CS improvements at spatial frequencies 3 and 6 cpd, with 0.28 logCS (P = .004) and 0.31 logCS (P = .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, noninvasive pharmacological treatment to improve vision in patients with early-stage cataract.

9.
Can J Ophthalmol ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39182514

RESUMEN

OBJECTIVE: To compare the efficiency of venturi and peristaltic pump phacoemulsification systems in patients undergoing routine laser cataract surgery. DESIGN: Single center, nonrandomized clinical study. PARTICIPANTS: The study compared consecutive eyes with moderate nuclear sclerosis undergoing routine laser cataract surgery at the Outpatient Eye Center, Mercy Health System, Springfield, MO, USA. METHODS: Each surgery used the same femtosecond laser settings. Surgeries were performed with either a venturi or peristaltic vacuum system by a single surgeon (WJS). The EFX, percent power, ultrasound time (UST), the total time that the phaco tip was in the eye (phaco tip in/out time, PIOT), and the surgery time (speculum in/out time) were recorded. Exclusions and intraoperative complications were also analyzed. RESULTS: 995 eyes were included in the study. The EFX in the venturi eyes (1.7 ± 1.3; n = 521) compared to peristaltic eyes (2.1 ± 1.4; n = 474) was lower (p < 0.0001). Similarly, the UST in the eyes performed with the venturi system versus the peristaltic system was reduced (32.4 ± 22.3 s vs 40.7± 25.7 s; p < 0.0001). The PIOT in the venturi group compared to the peristaltic group was less (71.1 ± 31.1 sec vs 79.1 ± 36.1 s; p = 0.0002). The case time (speculum in/out time) was lower for the venturi eyes (307.2 ± 68.8 s vs. 311.6 ± 53.6 s; p = 0.268). CONCLUSION: In eyes undergoing routine laser cataract surgery, the use of the venturi pump system was more efficient compared to the peristaltic pump system based on energy use and time, and there was no significant difference in complications.

10.
Neuropharmacology ; 257: 110030, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38851531

RESUMEN

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.


Asunto(s)
Anfetaminas , Alucinógenos , Corteza Prefrontal , Animales , Masculino , Alucinógenos/farmacología , Alucinógenos/administración & dosificación , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/fisiología , Ratones , Anfetaminas/farmacología , Anfetaminas/administración & dosificación , Neuronas/efectos de los fármacos , Neuronas/fisiología , Ratones Endogámicos C57BL , Conducta Animal/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología
11.
Acta Ophthalmol ; 102(5): e696-e704, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38155407

RESUMEN

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.


Asunto(s)
Biometría , Lentes Intraoculares , Óptica y Fotónica , Refracción Ocular , Agudeza Visual , Humanos , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Anciano de 80 o más Años , Refracción Ocular/fisiología , Femenino , Masculino , Biometría/métodos , Agudeza Visual/fisiología , Factores de Edad , Implantación de Lentes Intraoculares/métodos , Facoemulsificación/métodos , Reproducibilidad de los Resultados
12.
Med Devices (Auckl) ; 17: 339-348, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39434832

RESUMEN

Purpose: This study aims to investigate the differences between the heat energy produced during cataract surgery and Cumulative dissipated energy (CDE). CDE is often used as a medium for understanding the energy delivered to the eye during cataract surgery. However, the actual energy produced at the tip level of the tip is not well understood. We propose that a discrepancy may exist between the CDE reported by the surgical machine and the actual energy delivered to the eye. Methods: About 50 mL of distilled water were degassed and placed in an isobaric calorimeter. Using the Alcon Centurion and Ozil handpiece fitted with the balanced tip, an investigator immersed the phaco tip into the water and pressed the foot pedal to position 3. The device was set to 100% continuous power, vacuum to 0 mmHg, with aspiration 12 mL/min aspiration. To prevent system changes in the system within the calorimeter, the aspiration tubing was occluded. Temperature change recorded by another investigator was observed from 0 to 60 seconds. After 60 seconds the first researcher immediately released the pedal and removed the phaco tip from the water. Trials were performed 10 times using solely torsional or longitudinal settings and averaged. CDE also was recorded and averaged. Results: No significant difference was seen in the temperature change or energy calculated in Joules between ultrasound modalities, with torsional producing a magnitude of 163 J and longitudinal producing 172 J (P = 0.2). However, the CDE generated in the 60 seconds period was significantly different, with a magnitude of 61 for longitudinal compared to 24 for torsional (P < 0.001). Conclusion: Significantly more energy was generated using torsional ultrasound than longitudinal at the tip level of the tip. CDE did not appear to accurately reflect these differences. This suggests that other factors should be considered when evaluating CDE and surgical outcomes.


This study looked at possible differences between the energy generated during cataract surgery that is reported by the surgical device and the actual energy measured as thermal heat using different machine settings, namely longitudinal and torsional ultrasound. A common metric used for energy delivery to the eye is cumulative dissipated energy. The problem is that this measure accounts for the energy delivered to the eye where the surgical instrument passes through the cornea. Energy that is produced by the rest of the instrument that is inside the eye is less understood, although others have studied postoperative outcomes. We used a method called calorimetry to measure the thermal heat produced by the entire tip and compared this to what the machine reported as cumulative dissipated energy. Calorimetry calculates energy by measuring the change in temperature of liquids. The surgical instrument generated heat in a chamber containing water, and we used the change in temperature to calculate the energy produced by the surgical instrument. We found that longitudinal and torsional ultrasound produced similar heat energy, but the machine reported very different energy. Our results suggest that the machine may not be reporting all of the energy which the surgical instrument produces, and that surgeons may not be able to rely on cumulative dissipated energy to predict operative outcomes.

13.
Eye (Lond) ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39322767

RESUMEN

OBJECTIVES: To analyse the accuracy of artificial intelligence (AI)-driven intraocular (IOL) calculation formulae, together with established formulae using the heteroscedastic methodology and the Eyetemis Analysis Tool. METHODS: Data from 404 eyes who underwent uneventful phacoemulsification with implantation of the SN60WF IOL were retrospectively reviewed. IOL power calculations were performed using the Barrett Universal II (BUII), EVO 2.0, Hoffer QST, K6, Ladas Super Formula (LSF), Nallasamy, PEARL-DGS and RBF 3.0 formulae. The SD of the prediction error (PE), served as the primary metric for accuracy. The mean absolute deviation (MAD) and the predictability rates within intervals from ±0.25 D to ±1.50 D were also evaluated. The Eyetemis Analysis Tool was used for further validation. RESULTS: The SD ranged from 0.468 (Nallasamy) to 0.510 (LSF). The Nallasamy formula had a significantly lower SD than the BUII (0.505, p = 0.025) and K6 (0.489, p = 0.022) formulae. The Nallasamy formula also exhibited the lowest MAD (0.358) with a significant difference compared with the Hoffer QST formula (0.384, p < 0.001). Finally, a significantly higher percentage of eyes achieving ± 0.50 D of the target refraction was seen using the Nallasamy formula (77.19%) compared with the Hoffer QST (71.04%, p = 0.019) and Ladas Super Formula (70.79%, p = 0.030) formulae. CONCLUSIONS: The Nallasamy formula, incorporating AI technology, demonstrated superior accuracy according to the analysis guidelines for PE statistics for non-gaussian datasets recommended by Holladay et al. and the online Eyetemis Analysis Tool.

14.
bioRxiv ; 2023 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-36712091

RESUMEN

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.

15.
Neuropsychopharmacology ; 48(7): 1011-1020, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36807609

RESUMEN

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.


Asunto(s)
Alucinógenos , Psilocibina , Masculino , Femenino , Animales , Ratas , Psilocibina/farmacología , Psilocibina/uso terapéutico , Ketanserina/farmacología , Alucinógenos/farmacología , Ansiedad , Antagonistas del Receptor de Serotonina 5-HT2 , Serotonina , Cognición
16.
J Cataract Refract Surg ; 49(10): 1056-1060, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37057705

RESUMEN

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.

17.
Clin Ophthalmol ; 17: 2341-2347, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37600145

RESUMEN

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.

18.
Clin Ophthalmol ; 17: 191-195, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36660311

RESUMEN

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.

19.
Can J Ophthalmol ; 58(6): 507-512, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-35868436

RESUMEN

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.


Asunto(s)
Contractura , Facoemulsificación , Humanos , Combinación de Medicamentos , Sulfatos de Condroitina , Ácido Hialurónico
20.
Clin Ophthalmol ; 17: 555-560, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36798796

RESUMEN

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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