Inhibition of the Casein-Kinase-1-Epsilon/Delta Prevents Relapse-Like Alcohol Drinking

During the past decade, it has been shown that circadian clock genes have more than a simple circadian time-keeping role. Clock genes also modulate motivational processes and have been implicated in the development of psychiatric disorders such as drug addiction. Recent studies indicate that casein-kinase 1ɛ/δ (CK1ɛ/δ)—one of the components of the circadian molecular clockwork—might be involved in the etiology of addictive behavior. The present study was initiated to study the specific role of CK1ɛ/δ in alcohol relapse-like drinking using the ‘Alcohol Deprivation Effect'' model. The effect of CK1ɛ/δ inhibition was tested on alcohol consumption in long-term alcohol-drinking rats upon re-exposure to alcohol after deprivation using a four-bottle free-choice paradigm with water, 5%, 10%, and 20% ethanol solutions, as well as on saccharin preference in alcohol-naive rats. The inhibition of CK1ɛ/δ with systemic PF-670462 (0, 10, and 30 mg/kg) injections dose-dependently decreased, and at a higher dosage prevented the alcohol deprivation effect, as compared with vehicle-treated rats. The impact of the treatment was further characterized using nonlinear regression analyses on the daily profiles of drinking and locomotor activity. We reveal that CK1ɛ/δ inhibition blunted the high daytime alcohol intake typically observed upon alcohol re-exposure, and induced a phase shift of locomotor activity toward daytime. Only the highest dose of PF-670462 shifted the saccharin intake daily rhythm toward daytime during treatment, and decreased saccharin preference after treatment. Our data suggest that CK1 inhibitors may be candidates for drug treatment development for alcoholism.     

Phenotyping interindividual variability in obstructive sleep apnoea response to temazepam using ventilatory chemoreflexes during wakefulness

Centrally active agents have a variable impact in patients with obstructive sleep apnoea (OSA) that is unexplained. How to phenotype the individual OSA response is clinically important, as it may help to identify who will be at risk of respiratory depression and who will benefit from a centrally active agent. Based on loop gain theory, we hypothesized that OSA patients with higher central chemosensitivity have higher breathing instability following the use of a hypnosedative, temazepam. In 20 men with OSA in a double‐blind, placebo‐controlled cross‐over trial we tested the polysomnographically (PSG) measured effects of temazepam 10 mg versus placebo on sleep apnoea. Treatment nights were at least 1 week apart. Ventilatory chemoreflexes were also measured during wakefulness in each subject. The patients (mean ± standard deviation; 44 ± 12 years) had predominantly mild‐to‐moderate OSA [baseline apnoea–hypopnoea index (AHI) = 16.8 ± 14.1]. Patients’ baseline awake central chemosensitivity correlated significantly with both the change of SpO₂ nadir between temazepam and placebo (r = ?0.468, P = 0.038) and oxygen desaturation index (ODI; r = 0.485, P = 0.03), but not with the change of AHI (r = 0.18, P = 0.44). Peripheral chemosensitivity and ventilatory recruitment threshold were not correlated with the change of SpO₂ nadir, ODI or AHI (all P > 0.05). Mild–moderate OSA patients with higher awake central chemosensitivity had greater respiratory impairment during sleep with temazepam. Relatively simple daytime tests of respiratory control may provide a method of determining the effect of sedative–hypnotic medication on breathing during sleep in OSA patients.     

Substance use and abuse in first-episode psychosis: prevalence before and after early intervention

Despite the high prevalence of substance abuse among first-episode psychosis (FEP) populations, few studies examine whether early intervention (EI) improves substance abuse. OBJECTIVE: To examine the prevalence and pattern of substance use and abuse among an FEP sample over 12 months. METHODS: All the participants were diagnosed with a first episode of a schizophrenia spectrum disorder. The participants were followed prospectively. The prevalence rates of substance use and abuse from this sample were compared before and after 12 months of EI services and were compared with rates observed in a sample from the general population. RESULTS: A total of 200 participants (80.0% males; mean age 24 years) entered the study: 183 participants completed all the assessments at baseline, 131 participants completed all the assessments at 12 months. At baseline, the findings showed similar prevalence rates between the FEP sample and the general sample for lifetime cannabis use (60% vs 55%, respectively) and hazardous alcohol use (26% vs 21%) but significantly different prevalence rates for lifetime hallucinogen (29% vs 15%; P < .001) and cocaine use (20% vs 14%; P < .001). At 12 months, the prevalence rates for drug abuse (P < .01), hazardous alcohol use (P < .01), and concurrent drug abuse and hazardous alcohol use (P < .05) were significantly lower than at baseline. CONCLUSION: Substance use and abuse decreased significantly after 12 months of EI services; EI services may be able to detect and to reduce substance use among FEP patients before it becomes a more serious disorder.     

Noninvasive assessment of visco-elasticity in the presence of accumulated soft tissue fluid

BACKGROUND: The diagnosis of compartment syndrome is made by clinical examination, but direct compartmental measurements are important and serve an adjunctive role in establishing the diagnosis. This study examines a noninvasive screening method for differentiating compartmental syndrome from edema without elevated internal pressure. MATERIALS AND METHODS: The study groups consisted of 16 normals, 22 subjects with edema, and 2 subjects with compartmental syndrome. Force-displacement curves on the posterior and anterior surface of the extremity at mid-calf of each extremity were recorded using a noninvasive mechanical tester. A cyclic force peaking at 120 N was applied over a skin area of 1.5 cm(2). In a uniform applied force environment, the peak force would be comparable to an applied pressure of 60 mm Hg. Mechanical parameters associated with tissue softness (SOFT), degree of hysteresis, and departure from linear elastic behavior were calculated. In seven subjects, direct intracompartment pressure readings were obtained by the Stryker method. RESULTS: Posterior SOFT was significantly larger than anterior SOFT, as expected, for all study groups, except those with compartmental syndrome. SOFT for subjects with compartment syndrome fell below the 99% confidence interval of all other groups in the affected compartment(s). Departure from linear elastic behavior values were also depressed in the posterior compartment for subjects with compartment syndrome as compared with the other groups. Degree of hysteresis was significantly increased for pitting edema. Extremities with nonpitting edema were not distinguishable from normal extremities for the levels of applied pressure used in this study. CONCLUSION: Noninvasively measured mechanical properties were significantly different between normal tissues and tissues with pitting and nonpitting edema. The mechanical properties of the extremity with compartmental syndrome were different than those with edema as well as normal extremities. A noninvasive mechanical tester is seen as a possible clinical tool to diagnose and monitor compartmental syndrome.     

Comparing the effects of root surface scaling with ultrasound instruments and Er,Cr:YSGG laser

There are several studies done to show the comparability of laser scaling and root planing with routine methods. The most suitable wavelengths for such an application are reported as 2,940 and 2,780 nm. The superficial interactions of the current wavelength with root surface is investigated in this study to compare the crater and crack formation during the procedures between ultrasound and Er,Cr:yttrium-scandium-gallium garnet (YSGG; 2,780 nm) laser-treated teeth. Thirty human teeth with calculus on their root surface, which were extracted because of the severe periodontitis, were selected for this interventional in vitro study. Calculus area were divided into two equal parts: One of them was prepared for Er,Cr:YSGG (Biolase, Waterlase, USA) laser irradiation and the other one for ultrasound treatment (Dentsply cavitron, DENTSPLY International, USA). The Er,Cr:YSGG laser was specified as follows: pulse energy = 50 mJ, power = 1 W, wavelength = 2,780 nm, pulse repetition rate = 20 pulse per seconds, tip length = 6 mm, and tip diameter = 600 microm. Nineteen of the laser samples (95%) and eight of ultrasound ones (40%) out of 20 samples in each group had craters showing a statistical significant difference (p < 0.001). The number and depth of these craters are also evaluated. Thirteen samples of the laser cases (65%) and all samples of the ultrasound group showed cracks with significant differences (p = 0.008). In addition, the number and width of cracks in both groups are reported. As a general conclusion, the laser-treated samples show more craters but less cracks.     

Condition-Specific Pamphlets to Improve End-of-life Communication in Long-term Care: Staff Perceptions on Usability and Use

Objectives

This article reports findings on the usability and staff use of 5 condition- specific pamphlets of high prevalence in long-term care (LTC): dementia, heart failure, chronic obstructive pulmonary disease, renal failure, and frailty. The pamphlets were created in response to residents', families', and staff's recommendations for activating early reflections and communication about end-of-life care.

Microkeratome-assisted posterior lamellar keratoplasty in pseudophakic and aphakic corneal edema

PURPOSE: To evaluate the outcome of microkeratome-assisted posterior lamellar keratoplasty for replacing diseased endothelium in pseudophakic and aphakic corneal edema. METHODS: Microkeratome-assisted posterior lamellar keratoplasty was performed on 10 eyes with pseudophakic or aphakic corneal edema. A nasal hinged 130- to 250-microm-thick flap was created with an automated microkeratome. The underlying 7.0-mm trephined button of deep stroma and endothelium was substituted with the same size donor button prepared by removing a same-sized flap and trephination of the remaining donor bed. The donor lenticule was fixated without sutures in position; the retracted flap was repositioned and sutured to the peripheral recipient tissue. The viscoelastic content of the anterior chamber was replaced by air to hold the graft in position. RESULTS: All surgeries were uneventful except for one case of donor button posterior dislocation forming a secondary anterior chamber, which was corrected through donor button exchange 1 month postoperatively. All uncomplicated cases had stable refraction and corneal topography as early as 1 month after surgery, which was maintained in follow-up examinations. In two eyes, corneal astigmatism > 5.00 diopters was recorded. One case of prolonged re-epithelialization and two cases of epithelial interface ingrowth occurred. CONCLUSIONS: Microkeratome-assisted posterior lamellar keratoplasty is an alternative to conventional penetrating keratoplasty for patients with diseased corneal endothelium, significantly reducing the time of visual rehabilitation. Determination of the relative advantages of this technique over penetrating keratoplasty and other recent alternative endothelial graft procedures relies on controlled prospective studies.     

Bevacizumab inhibits corneal neovascularization in an alkali burn induced model of corneal angiogenesis

BACKGROUND: New and uncontrolled blood vessel development in the cornea is a pivotal process in the pathogenesis of several corneal diseases. These corneal diseases may finally cause blindness and managing them therapeutically is problematic. The data supporting a causal role for vascular endothelial growth factor in corneal neovascularization are extensive. This study aimed to evaluate the effect of subconjunctival bevacizumab (Avastin) on experimental corneal neovascularization in rabbits. METHODS: Chemical cauterization of the cornea was performed by touching central cornea with a 5-mm-diameter NaOH-soaked cotton applicator for 10 s in 20 eyes of 20 White New Zealand rabbits. The rabbits were then divided randomly into two equal groups. Bevacizumab (2.5 mg) was administered to 10 eyes (group 1) by a subconjunctival injection immediately after chemical cauterization of corneal surface. As a control, 10 eyes (group 2) received an injection of distilled water. Rabbits were examined daily for detection of the first signs of neovascularization. Three weeks later, the extent of corneal neovascularization was evaluated by direct examination and photograph analyses. Total corneal neovascularization area, degree of circumference involved and longest neovascular pedicle length were assessed. RESULTS: Bevacizumab significantly decreased the total neovascularization area (P < 0.009), the circumference involved (P < 0.011) and the longest neovascular pedicle length (P < 0.023). CONCLUSION: Local injection of bevacizumab has a significant effect on inhibition of alkali burn-induced corneal neovascularization. This shows the potential value of bevacizumab in the treatment of corneal neovascularization.