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Background and Purpose: Inhibition of the G-protein gated ACh-activated inward rectifier potassium current, I-K,I-ACh may be an effective atrial selective treatment strategy for atrial fibrillation (AF). Therefore, the anti-arrhythmic and electrophysiological properties of a novel putatively potent and highly specificI(K,ACh)inhibitor, XAF-1407 (3-methyl-1-[5-phenyl-4-[4-(2-pyrrolidin-1-ylethoxymethyl)-1-piperidyl]thieno[2,3-d]pyrimidin-6-yl]azetidin-3-ol), were characterised for the first time in vitro and investigated in horses with persistent AF.Experimental Approach: The pharmacological ion channel profile of XAF-1407 was investigated using cell lines expressing relevant ion channels. In addition, eleven horses were implanted with implantable cardioverter defibrillators enabling atrial tachypacing into self-sustained AF. The electrophysiological effects of XAF-1407 were investigated after serial cardioversions over a period of 1 month. Cardioversion success, drug-induced changes of atrial tissue refractoriness, and ventricular electrophysiology were assessed at baseline (day 0) and days 3, 5, 11, 17, and 29 after AF induction.Key Results: XAF-1407 potently and selectively inhibited K(ir)3.1/3.4 and K(ir)3.4/3.4, underlying theI(K,ACh)current. XAF-1407 treatment in horses prolonged atrial effective refractory period as well as decreased atrial fibrillatory rate significantly (similar to 20%) and successfully cardioverted AF, although with a decreasing efficacy over time. XAF-1407 shortened atrioventricular-nodal refractoriness, without effect on QRS duration. QTc prolongation (4%) within 15 min of drug infusion was observed, however, without any evidence of ventricular arrhythmia.Conclusion and Implications: XAF-1407 efficiently cardioverted sustained tachypacing-induced AF of short duration in horses without notable side effects. This supportsI(K,ACh)inhibition as a potentially safe treatment of paroxysmal AF in horses, suggesting potential clinical value for other species including humans.

Spinal control at intervertebral levels is dependent on interactions between the active, passive and neural control elements. However, this has never been quantifiable, and has therefore been outside the reach of clinical assessments and research. This study used fluoroscopy during repeated unconstrained flexion and return neck movements to calculate intersegmental motor control (MC), defined as the difference and variation in repeated continuous angular motion from its average path. The study aimed to determine control values for MC at individual levels and its variability. Twenty male volunteers aged 19–29 received fluoroscopic screening of their cervical spines during 4 repetitions of neutral to full flexion and return motion. Moving vertebral images from C0–C1 to C6–C7 were tracked using cross-correlation codes written in Matlab. MC for each level was defined as the mean of the absolute differences between each repetition’s angular path and their mean and its variability as represented by the SD. 1-way ANOVA and Tukey multiple comparisons were used to identify significant contrasts between levels. The mean MC differences and SDs were highest at C1-2, suggesting that this level has the least control and the most variability. Results at this level alone were highly significant (F-ratio 10.88 and 9.79 P

Background Over a third of preadolescent children with overweight or obesity. The American Academy of Pediatrics (AAP) recommends pediatric providers help families make changes in eating and activity to improve body mass index (BMI). However, implementation is challenging given limited time and referral sources, and family burden to access in-person weight management programs. Purpose To describe the design of a National Heart Blood and Lung Institute sponsored cluster randomized controlled pediatric-based trial evaluating the effectiveness of the Fitline pediatric practice-based referral program to reduce BMI and improve diet and physical activity in children with overweight or obesity. Comparison will be made between brief provider intervention plus referral to (1) eight weekly nutritionist-delivered coaching calls with workbook to help families make AAP-recommended lifestyle changes (Fitline-Coaching), vs. (2) the same workbook in eight mailings without coaching (Fitline-Workbook). Methods Twenty practices are pair-matched and randomized to one of the two conditions; 494 parents and their children ages 8–12 with a BMI of ≥85th percentile are being recruited. The primary outcome is child BMI; secondary outcomes are child's diet and physical activity at baseline and 6- and 12-months post-baseline. Cost-effectiveness of the two interventions also will be examined. Conclusion This is the first randomized controlled trial to examine use of a centrally located telephonic coaching service to support families of children with overweight and obesity in making AAP-recommended lifestyle changes. If effective, the Fitline program will provide an innovative model for widespread dissemination, setting new standards for weight management care in pediatric practice. Trial registration: The ClinicalTrials.gov registration number is NCT03143660 .

BackgroundIn clinical diagnosis, the largest motion associated with cervical range of motion is thought to be found at end-range and it is this perception that forms the basis for the interpretation of flexion/extension studies. There have however, been representative cases of joints producing their maximum motion before end-range, but this phenomenon is yet to be quantified. PurposeTo provide a quantitative assessment of the difference between maximum motion and end-range in healthy subjects. Secondarily to classify joints into type based on their motion and to assess the proportions of these joint types. Study designThis is an observational study. Subject sampleThirty three healthy subjects participated in the study. Outcome measuresMaximum motion, end-range motion and surplus motion in degrees were extracted from each cervical joint. MethodsThirty-three subjects performed one flexion and one extension motion excursion under video fluoroscopy. The motion excursions were divided into 10 percent epochs between the initial upright position and the end-range position, from which maximum motion, end-range and surplus motion were extracted. Surplus motion was then assessed in quartiles and joints were classified into type according to end-range. ResultsFor flexion 48.9% and for extension 47.2% of joints produced maximum motion before end-range (type Surplus). For flexion 45.9% and for extension 46.8% of joints produced maximum motion at end-range (type Classic) and 5.2% of joints in flexion and 6.1% of joints in extension concluded their motion anti-directionally (type Anti-directional). Mann-Whitney U tests produced significant results for C2/C3, C3/C4 and C4/C5 in flexion and C1/C2, C3/C4 and C6/C7 in extension when comparing end- range motion for type Classic and type Surplus. The average contributions to cervical range-of-motion (ROM) (C0 to C7) for flexion and extension were 60.23֯ and 67.86֯ for type Classic and 42.22֯ and 49.05֯ for type Surplus respectively. Thus, the average contribution to cervical ROM was larger for type Classic than for type Surplus. The average pro-directional surplus motion was 2.41֯ ± 2.12֯ with a range of range (0.07֯ -14.23֯) for flexion and 2.02֯ ± 1.70֯ with a range of 0.04°-6.97° for extension.ConclusionThis is the first study to categorise joints by type of motion. Type Surplus constituted approximately half of the joints analysed in this study. Therefore, end-range motion cannot be assumed to be a demonstration of a joint´s maximum motion.

BACKGROUND: Pharmacological treatment of atrial fibrillation (AF) in horses can be challenging because of low efficacy and adverse effects. Flecainide has been tested with variable efficacy.OBJECTIVE: To test whether the efficacy of flecainide is dependent on AF duration.ANIMALS: Nine Standardbred mares.METHODS: Factorial study design. All horses were instrumented with a pacemaker and assigned to a control or an AF group. On day 0, all horses were in sinus rhythm and received 2 mg/kg flecainide IV. Atrial fibrillation subsequently was induced in the AF group by pacemaker stimulation. On days 3, 9, 27, and 55, flecainide was administered to all horses, regardless of heart rhythm.RESULTS: All horses in AF cardioverted to sinus rhythm on days 3 and 9. On day 27, 5/6 horses cardioverted, whereas only 2/6 cardioverted on day 55. The time from the start of flecainide infusion to cardioversion (range, 3-185 min, log transformed) showed linear correlation with the cumulative duration of AF (r 2 = .80, P CONCLUSIONS AND CLINICAL IMPORTANCE: Flecainide is effective for cardioversion of short-term induced AF, but the effect decreases with AF duration. Controlling heart rate may minimize adverse effects caused by flecainide, but the drug should be used with great caution.

Impaired sensorimotor ability has been demonstrated in recurrent neck pain patients. It is however not clear if cervical joint motion and pressure pain sensitivity in recurrent neck pain patients are different from asymptomatic controls.Cervical flexion and extension motions were examined by video-fluoroscopy and pressure pain thresholds were assessed bilaterally over C2/C3, C5/C6 facet joints and right tibialis anterior in eighteen recurrent neck pain patients and eighteen healthy subjects. Individual joint motion was analyzed by dividing fluoroscopic videos into 10 epochs. The motion opposite to the primary direction (anti-directional motion) and motion along with the primary direction (pro-directional motion) of each joint were extracted across epochs. Total joint motion was the sum of anti-directional and pro-directional motions. Joint motion variability was represented by the variance of joint motions across epochs.Compared to controls, recurrent neck pain patients showed: 1) decreased anti-directional motion at C2/C3 and C3/C4 (P 0.05) and increased anti-directional motion at C5/C6 and C6/C7 (P 0.05) during extension motion. 2) Increased overall anti-direction motion during flexion motion (P 0.05). 3) Lower joint motion variability at C3/C4 during extension motion (P 0.05).Recurrent neck pain patients showed a redistribution of anti-directional motion between the middle cervical spine and the lower cervical spine during cervical extension and increased overall anti-directional motion during cervical flexion compared with healthy controls. The anti-directional motion was more sensitive to neck pain compared to other cervical joint motion parameters in the present study.

The American Academy of Pediatrics (AAP) recommends a staged approach to pediatric weight management, starting with helping families to make targeted dietary and activity changes. This pilot study evaluated the preliminary efficacy of a pediatric practice-based referral program to support parents in helping their overweight/obese children improve their weight-related behaviors and BMI.A nonrandomized intervention study with contemporaneous control was used. Parents and their children ages 8-12 with BMI ≥85th percentile (N = 37) were recruited from a pediatric practice serving a low-income, multiethnic population. Providers delivered brief intervention and referred families to six weekly FITLINE telephone counseling sessions with a nutritionist who guided parents in helping their child make AAP-recommended changes. Child BMI and parent survey of child diet and physical activity were completed at baseline and 3 months. Medical record data from 44 children matched for age and BMI were collected.Mean change in BMI from baseline to 3-month follow-up was -0.49 BMI units (standard deviation [SD], 0.95; p = 0.007) for the FITLINE group and 0.35 BMI units (SD, 0.96; p = 0.02) for the control group. Adjusting for baseline BMI, age, and sex, children in the FITLINE condition reduced BMI significantly more than children in the control condition (mean difference = -0.89; p = 0.0003). Significant improvements in many dietary and sedentary behaviors also were noted.The FITLINE program reduced short-term BMI and improved dietary and sedentary behaviors. A randomized, controlled trial is warranted to assess the program's efficacy and potential to serve as a model for reducing obesity in pediatric practice.

Background: Atrial fibrillation (AF) is the most common arrhythmia affecting performance in horses. However, no previous studies have quantified the performance reduction in horses suffering from AF. Objectives: To quantify the effect of AF on maximum velocity (Vmax), maximum heart rate (HRmax), heart rate recovery (T100), hematologic parameters and development of abnormal QRS complexes. Animals: Nine Standardbred trotters. Methods: Two-arm controlled trial. Six horses had AF induced by means of a pacemaker and 3 served as sham-operated controls. All horses were subjected to an exercise test to fatigue before (SET1) and after (SET2) 2 months of AF or sham. The Vmax and HRmax were assessed using a linear mixed normal model. Abnormal QRS complexes were counted manually on surface ECGs. Results: Atrial fibrillation resulted in a 1.56 m/sec decrease in Vmax (P max ± SD increased from 226 ± 11 bpm at SET1 to 311 ± 27 bpm at SET 2. The AF group had higher HRmax at SET2 compared with controls (P

Background The worksite represents a promising venue in which to address the issue of obesity. Design Pair-matched, cluster-RCT. Data were collected from 2005 to 2008 and analyzed in 2008. Setting/participants A random sample of 806 employees was selected to represent the workforce of six hospitals in central Massachusetts. Intervention The 2-year ecologic intervention sought to prevent weight gain through changes in worksite weight-related norms using strategies targeted at the organization, interpersonal environment, and employees. Main outcome measures The primary outcome was change in BMI at the 12- and 24-month follow-ups. Change in perceptions of organizational commitment to employee health and normative coworker behaviors were secondary outcomes. Results There was no impact of the intervention on change in BMI from baseline to 12 (β=0.272; 95% CI=−0.271, 0.782) or 24 months (β=0.276; 95% CI=−0.338, 0.890) in intention-to-treat analysis. When intervention exposure (scale=0 to 100) was used as the independent variable, there was a decrease of 0.012 BMI units (95% CI=−0.025, 0.001) for each unit increase in intervention participation at the 24-month follow-up. Employees in intervention sites reported significantly greater improvements in perceptions of organizational commitment to employee health at 12 and 24 months compared to control sites, but there was no impact on perceptions of normative coworker behaviors. Conclusions The intervention had a dose–response relationship with BMI, with positive effects proportional to extent of participation. Although the intervention was able to change organizational perceptions, successfully improving changes in actual and perceived social norms may be needed to achieve population-level impact in complex worksite organizations.

Previous studies have consistently observed that women are more likely to perceive themselves as overweight compared to men. Similarly, women are more likely than men to report trying to lose weight. Less is known about the impact that self-perceived weight has on weight loss behaviors of adults and whether this association differs by gender. We conducted a cross-sectional analysis among an employee sample (n=899) to determine the association of self-perceived weight on evidence-based weight loss behaviors across genders, accounting for body mass index (BMI) and demographic characteristics. Women were more likely than men to consider themselves to be overweight across each BMI category, and were more likely to report attempting to lose weight. However, perceiving oneself to be overweight was a strong correlate for weight loss attempts across both genders. The effect of targeting accuracy of self-perceived weight status in weight loss interventions deserves research attention.

OBJECTIVES Considerable evidence has shown that diet can affect both the incidence and the progression of prostate cancer. The objective of this study was to determine whether men in this situation could make a change to a diet emphasizing plant-based foods and fish and to examine the effect on quality of life (QOL) and prostate-specific antigen (PSA) velocity. METHODS A total of 36 men and their partners were randomly assigned to attend a series of 11 dietary and cooking classes that also integrated mindfulness practice as a support in making the change or a wait-list control group. Assessments were made of dietary intake, QOL, and PSA at baseline, after intervention (11 weeks), and 3 months after intervention. RESULTS The intervention group showed significant reductions in the consumption of saturated fat and increased consumption of vegetable proteins with accompanying reductions in animal proteins, including dairy products. They also showed increased QOL. Although no significant change was found in the rate of PSA increase between the two groups, the mean PSA doubling time for the intervention group was substantially longer at the 3-month follow-up visit than that of the controls. CONCLUSIONS Men with a increasing PSA level after primary treatment were able to make a change to a prostate-healthy diet, accompanied by increases in QOL. No significant difference was found in the log PSA slope between the two groups; however, the PSA doubling time increased substantially in the intervention group compared with that in the controls. Future trials should examine the effect of the prostate-healthy diet with a larger sample of men for a longer period.

This study examined baseline dietary intake, body weight, and physiologic status in patients enrolled in a dietary intervention for type 2 diabetes mellitus (T2DM).Dietary, physiologic, and demographic information were collected at baseline from 40 adult patients with poorly controlled T2DM (glycosylated hemoglobin7%) who participated in a clinical trial at an academic medical center in Worcester, Massachusetts, USA.The average age at enrollment was 53.5 y (SD 8.4), average body mass index was 35.48 kg/m(2) (SD 7.0), and glycosylated hemoglobin was 8.3% (SD 1.2). Participants were predominantly white, married, and employed full time. Forty-eight percent were men. Seventy-eight percent had hyperlipidemia, and 68% had hypertension. Reported baseline daily average energy intake was 1778 kcal (SD 814), daily carbohydrate was 159 g (SD 71.5), and dietary fiber was 11.4 g (SD 5.2). The dietary composition was 35% carbohydrate, 45% fat (15% saturated fat), and 20% protein. The American Diabetes Association (ADA) guidelines recommends 45-65% of energy from carbohydrate, 20-35% from fat (7% saturated), and 20% from protein.These patients reported a low-carbohydrate, low-fiber, high-fat (especially saturated) diet, although they stated they are not following any of the popular low-carbohydrate diets. Patients with T2DM may find the current trend toward reducing weight through low-carbohydrate diets attractive for control of blood glucose, despite ADA recommendations. This dietary pattern may represent a popular trend that extends beyond our particular study and, if so, has serious cardiovascular implications in this vulnerable population of T2DM patients.