Author Correction: Inhibition of casein kinase 1δ/εimproves cognitive-affective behavior and reduces amyloid load in the APP-PS1 mouse model of Alzheimer's disease.

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Inhibition of casein kinase 1δ/εimproves cognitive-affective behavior and reduces amyloid load in the APP-PS1 mouse model of Alzheimer's disease.

Circadian rhythm disruption is one of the earliest biomarkers of Alzheimer's disease (AD), and there exists a bidirectional relationship by which dysfunctions in the circadian clock drive AD pathology and AD pathology drives circadian dysfunction. Casein kinase 1 (CK1) isoforms ε and δ, key circadian regulators, are significantly upregulated in AD and may contribute to AD pathogenesis. In the current studies, we have examined how inhibition of CK1ε/δ with PF-670462 (at 10 mg/kg, δ isoform selective, or 30 mg/kg, δ and ε selective) impacts regional Aß and circadian gene expression in 10-13 month old APP-PS1 mice and nontransgenic controls. We have also assessed circadian, cognitive, and affective behavioral correlates of these neural changes. At baseline, APP-PS1 mice showed a short period, as well as impaired cognitive performance in both prefrontal cortex and hippocampus-dependent tasks. Both doses of PF-670462 lengthened the period and improved affect, whereas only the higher dose improved cognition. Further, PF-670462 treatment produced a dose-dependent reduction in amyloid burden - overall Aß signal decreased in all three areas; in the prefrontal cortex and hippocampus, PF-670462 also reduced plaque size. Together, these findings support chronotherapy as a potential tool to improve behavior in AD.

The circadian Per1 and Per2 genes influence alcohol intake, reinforcement, and blood alcohol levels.

BACKGROUND: Perturbations in the function of core circadian clock components such as the Period (Per) family of genes are associated with alcohol use disorder, and disruptions in circadian cycles may contribute to alcohol abuse and relapse. This study tested ethanol consumption, reinforcement, and metabolism in mice containing functional mutations in Per1 and/or Per2 genes on an ethanol-preferring background, C57BL/6J mice. METHODS: Mice were tested in: (A) free-access intake with ascending concentrations of ethanol (2-16%, v/v), (B) conditioned place preference using ethanol (2g/kg for males; 2.5g/kg for females) vs. saline injections, (C) recovery of the righting reflex following a 4g/kg bolus of ethanol, and (D) blood ethanol levels 1h after a 2g/kg bolus of ethanol. RESULTS: All Per mutant (mPer) mice showed increased ethanol intake and condition place preference compared to controls. There were also genotypic differences in blood ethanol concentration: in males, only mPer1 mice showed a significantly higher blood ethanol concentration than WT mice, but in females, all mPer mice showed higher blood ethanol levels than WT mice. CONCLUSIONS: Mutation of either Per1 or Per2, as well as mutations of both genes, increases ethanol intake and reinforcement in an ethanol-preferring mouse model. In addition, this increase in ethanol seeking behavior seems to result both from a change in ethanol metabolism and a change in reward responding to ethanol, but not from any change in sensitivity to ethanol's sedating effects.

Nicotine and extinction of fear conditioning.

Despite known health risks, nicotine use remains high, especially in populations diagnosed with mental illnesses, including anxiety disorders and Post-Traumatic Stress Disorder (PTSD). Smoking in these populations may relate to the effects of nicotine on emotional memories. The current study examined the effects of nicotine administration on the extinction of conditioned fear memories. C57BL/6J mice were trained with two white noise conditioned stimulus (CS; 30 s, 85 dB)-foot shock (2 s, 0.57 mA) pairings. Extinction sessions consisted of six presentations of the CS (60 s) across multiple days. Mice were either tested in an AAA design, in which all stages occurred in the same context, or in an ABA design to identify if context changes alter extinction. Saline or nicotine was administered 5 min before training and/or extinction. In the AAA design, nicotine administration before training did not alter extinction. Nicotine administered prior to extinction sessions enhanced extinction and nicotine administered before training and extinction decreased extinction. In the ABA design, nicotine administered before extinction enhanced extinction and blocked context renewal of conditioned fear, while nicotine administered during training and extinction did not alter extinction but enhanced the context renewal of conditioned fear. Nicotine has a differential effect on extinction of fear conditioning depending on when it is administered. Administration during extinction enhances extinction whereas administration during training and extinction may strengthen contextual fear memories and interfere with extinction.

Effects of two ultrasound devices and angles of application on the temperature of tissue phantom.

Ultrasound is a commonly used therapeutic modality for which there is little research on the effect of treatment dosage on the extent of tissue heating. The purpose of this study was to investigate the effect of two different ultrasound devices, angle of ultrasound application, and treatment time on the temperature of a tissue phantom. Four trials were performed at four ultrasound application angles (90 degrees, 80 degrees, 70 degrees, and 60 degrees) with both an Excel UltraMax and a Mettler Sonicator 720. A continuous 1-MHz frequency at 2.0 W/cm2 was administered for 5 minutes, with tissue phantom temperature recorded at 1-minute intervals. The analysis of the data revealed significant main effects between ultrasound devices, angle of application, and treatment times. Interactions were identified between ultrasound device and treatment times and angle of application and treatment times. Analysis of simple effects revealed significant differences between ultrasound devices after 2, 3, 4, and 5 minutes of treatment and between treatment times and 80 degrees and 60 degrees angles of application. Maximal temperature increase after a 5-minute treatment was 2.025 degrees C. This level of tissue heating falls below expected values and may not yield therapeutic results. The thermal effects were noted to be greatest at 80 degrees and 90 degrees angles of application. Despite appropriate calibration and identical treatment protocols, the two ultrasound devices yielded significantly different tissue phantom temperatures, which were notably lower than expected values. We concluded that direct monitoring of ultrasound device output and calculation of treatment dosage should occur on a routine basis, as treatment outcome will certainly be affected by the actual dosage of ultrasonic energy.

The effect of cryotherapy on eccentric plantar flexion peak torque and endurance.

OBJECTIVE: The effects of cryotherapy on eccentric torque production and muscle endurance have been controversial. Our intent was to examine the effect of cryotherapy on isokinetic eccentric plantar flexion peak torque at 30 degrees /sec and 120 degrees /sec and on endurance at 120 degrees /sec. DESIGN AND SETTING: SUBJECTS WERE TESTED ON AN ISOKINETIC DYNAMOMETER FOR PEAK TORQUE AND ENDURANCE AND WERE THEN RANDOMLY ASSIGNED TO ONE OF FOUR GROUPS: (a) peak torque measurements at 30 degrees /sec and 120 degrees /sec after a 30-minute 10 degrees C ice bath immersion, (b) peak torque measurements at 30 degrees /sec and 120 degrees /sec without ice bath immersion (control), (c) endurance measurement at 120 degrees /sec after a 30-minute 10 degrees C ice bath immersion, and (d) endurance measurement at 120 degrees /sec without ice bath immersion (control). Subjects completed each of the four experimental conditions with 7 to 14 days between conditions. SUBJECTS: Eleven male and 11 female volunteers (mean age, 23.8 +/- 3.5 years) were screened for normal ankle range of motion, past history of lower extremity injury, and contraindications to cryotherapy. MEASUREMENTS: Dependent t tests were used to analyze practice session data in order to establish reliable baseline measurements. A 2 x 2 analysis of variance (ANOVA) with repeated measures (p < .05) was used to analyze peak torque data. A one-way ANOVA (p < .05) was used to analyze endurance data in the form of total work. RESULTS: Velocity significantly affected peak torque production, with eccentric peak torque values significantly higher at 120 degrees /sec than at 30 degrees /sec for both the control and the immersion conditions. Cryotherapy had no effect on eccentric peak torque at either 30 degrees /sec or 120 degrees /sec, but it increased eccentric total work (endurance) at 120 degrees /sec. CONCLUSIONS: Cryotherapy has long been known to have beneficial therapeutic effects. In our study, cryotherapy did not significantly affect eccentric peak torque, but it did increase muscle endurance. An athlete can reap the beneficial effects of cryotherapy, such as pain reduction, vasoconstriction, and edema control, without compromising eccentric force production or endurance.

TCDD residues in fish and shellfish from U.S. waterways.

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) in the edible portion of fish and shellfish from various U.S. waterways has been monitored since 1979. Analytical results for the period 1979-1994 are reported. Extracts obtained after column chromatographic and liquid chromatographic cleanup were examined by electron capture detection-gas chromatography (GC), and final quantitation and confirmation were performed by GC/mass spectrometry with multiple ion detection. Analyses of 1623 test samples indicated that TCDD residues in fish and shellfish were not widespread but rather were localized in areas near waste sites, chlorophenol manufacturers, and pulp and paper mills. Analytical results indicated that levels in aquatic species from these sites have been declining steadily. No TCDD (limit of detection and confirmation, 1-2 ppt) has been found in recent years in aquatic species from most Atlantic, Pacific, and Gulf of Mexico sites and Great Lakes other than Lake Ontario and Saginaw Bay (Lake Huron).

Various treatment techniques on signs and symptoms of delayed onset muscle soreness.

Eccentric activities are an important component of physical conditioning and everyday activities. Delayed onset muscle soreness (DOMS) can result from strenuous eccentric tasks and can be a limiting factor in motor performance for several days after exercise. An efficacious method of treatment for DOMS would enhance athletic performance and hasten the return to activities of daily living. The purpose of this study was to identify a treatment method which could assist in the recovery of DOMS. In the selection of treatment methods, emphasis was directed toward treatments that could be rendered independently by an individual, therefore making the treatment valuable to an athletic trainer in team setting. DOMS was induced in 70 untrained volunteers via 15 sets of 15 eccentric contractions of the forearm extensor muscles on a Lido isokinetic dynamometer. All subjects performed a pilot exercise bout for a minimum of 9 weeks before data collection to assure that DOMS would be produced. Data were collected on 15 dependent variables: active and passive wrist flexion and extension, forearm girth, limb volume, visual analogue pain scale, muscle soreness index, isometric strength, concentric and eccentric wrist total work, concentric and eccentric angle of peak torque. Data were collected on six occasions: pre- and post-induced DOMS, 20 minutes after treatment, and 24, 48, and 72 hours after treatment. Subjects were randomly assigned to 1 of 7 groups (6 treatment and 1 control). Treatments included a nonsteroidal anti-inflammatory drug, high velocity concentric muscle contractions on an upper extremity ergometer, ice massage, 10-minute static stretching, topical Amica montana ointment, and sublingual A. montana pellets. A 7 x 6 ANOVA with repeated measures on time was performed on the delta values of each of the 15 dependent variables. Significant main effects (p < .05) were found for all of the dependent variables on time only. There were no significant differences between treatments. Therefore, we conclude that none of the treatments were effective in abating the signs and symptoms of DOMS. In fact, the NSAID and A. montana treatments appeared to impede recovery of muscle function.