Controlled evaluation of thermal biofeedback in treatment of elevated blood pressure in unmedicated mild hypertension

In the first of two studies, 42 unmedicated mild hypertensives completed either 16 sessions of thermal biofeedback (TBF) training for hand (7 sessions) and foot (9 sessions) warming or 8 weeks of monitoring BPs at home. There was a trend (p<.10) for more of those treated (57.1%) to have DBPs lower than 90 mm Hg than for those only monitoring BPs at home (33%). Analyses of clinic BP values from random zero sphygmomanometer measurements, from 24-hour ambulatory BP monitoring, and from home BP measurements made by the patient showed no advantage for treatment versus BP monitoring. Sixteen of the 21 patients in BP monitoring were later treated. Analyses of treatment effects across all treated subjects by gender revealed a significant (p=.02) decrease in DBP for treated female subjects (n=13) but not for males (n=24). In the second study the 22 initial treatment successes, that is, those whose DBP was below 90 mm Hg at posttreatment (59.4% of those who completed treatment), were randomized to an intensive follow-up (monthly visits for 6 months, then visits every two months) emphasizing regular home practice with an electronic TBF device or regular follow-up (visits every 3 months). Twelve of the 22 were still normotensive at 12 months. There were no differences at any point during the follow-up between the two conditions in success rate or BPs despite a numerical advantage in reported frequency of home practice by those in the intensive follow-up condition.This research was supported by a grant from NHLBI, HL-31189.     

How Many Nucleotides Are Required to Resolve a Phylogenetic Problem? The Use of a New Statistical Method Applicable to Available Sequences

The evolution of bootstrap proportions (BP) with sequence length was studied using a 28S ribosomal RNA data set. For different sequence lengths, informative sites were jackknifed several times. Bootstrapping was subsequently performed on each of these subsamples. For each node, BPs so obtained were plotted against sequence length, showing the evolution of the robustness with increasing number of informative sites. For robust nodes (BP of 100%), the pattern of BPs is unvarying and is described by a simple function BP = 100(1− e^{−b(x − x′)}), where x is the number of informative sites and b and x′ are two parameters estimated using a nonlinear regression procedure. When a node has a BP <100% and the pattern of BPs fits this function, it is possible to estimate the number of informative sites required to obtain a given average BP. The method also identifies nonrobust nodes (nonascending clusters of BP dots), for which it seems to be more cost effective and fruitful to turn to other species and/or genes rather than to continue sequencing longer gene lengths from the same species to reach a BP of 95%.     

Properties of human visual memory for block patterns

Several characteristics of human short-term visual memory (STVM) were specified through a series of experiments, by using block patters (BPs) of varying complexity and matrix size (n-by-n). For each matrix size, BPs with high and low complexity were formed (i.e.n-by-n-H andn-by-n-L). In experiment I, the characteristics of the acquisition process were examined through a recall task. The recall rate for a single glance (exposure time less than 0.3s) is more than 90% for 3-by-3 and 4-by-4-L BPs. For 4-by-4-H BPs, an improvement in recall rate was not found even when exposure time was increased to 2.4s. The recall rate for 6-by-6-H, 7-by-7, and 8-by-8 BPs did not change even when the exposure time was increased to 9s. In experiment II, the characteristics of the STVM decay process were examined using a recall task. Though a difference between the 4-by-4-L and 4-by-4-H acquisition rates was found, no difference was found in the forgetting rates. No decay was found for 6-by-6 BPs. Furthermore, the information obtained during a short duration was not forgotten for 4-by-4, and 6-by-6 BPs. It was concluded from these results that:1) The acquisition rate into STVM depends upon figural complexity.2) The decay rate does not depend upon figural complexity.3) The limit of STVM was between 4-by-4-L, and 4-by-4-H BPs.4) The recall performance for 6-by-6 BPs reflects the information stored in long-term visual memory. Although the acquisition rate into STVM depend upon figural complexity, it appeared in experiment IV that the number of subpatterns into which subjects segmented BPs when memorizing them was highly correlated with rated figural complexity. It also appeared that the number of memory chunks estimated from the data of interrecall-interval was not correlated with the complexity. Finally, a process model for visual memory for block patterns was proposed.     

Biofeedback-assisted relaxation therapy in neurocardiogenic syncope: a pilot study

This controlled pilot study explored the effects of biofeedback assisted relaxation (BFRT) in neurocardiogenic syncope. Twenty-two patients who completed a 2-week pretest, were randomized to either treatment or wait list control, followed by a 2-week posttreatment/control period. Treatment comprised electromyograph and thermal biofeedback, autogenic and progressive relaxation, and symptom-specific recommendations. Significant differences (p < .05) between groups were observed in the headache index and loss of consciousness, favoring the BFRT group. Both groups decreased state anxiety and depression. The Millon Behavioral Health Inventory was used to assess patients' coping style and adjustment to illness. The majority of the adult participants evidenced illness overreaction, preoccupation with illness, depressive feelings, and tendencies to nonadherence to therapy. BFRT is of potential benefit to patients with neurocardiogenic syncope, but further study is necessary to define the influence of coping style on outcome.     

Change Mechanisms Associated with Combined Relaxation/EMG Biofeedback Training for Chronic Tension Headache

Therapeutic mechanisms hypothesized to underlie improvements in tension headache activity achieved with combined relaxation and eleclromyographic (EMG) biofeedback therapy were examined. These therapeutic mechanisms included (1) changes in EMG activity in frontal and trapezii muscles, (2) changes in central pain modulation as indexed by the duration of the second exteroceptive silent period (ES2), and (3) changes in headache locus of control and self-efficacy. Forty-four young adults with chronic tension-type headaches were assigned either to six sessions of relaxation and EMG biofeedback training (N = 30) or to an assessment only control group (N = 14) that required three assessment sessions. Measures of self-efficacy and locus of control were collected at pre- and posttreatment, and ES2 was evaluated at the beginning and end of the first, third, and lost session. EMG was monitored before, during, and following training trials. Relaxation/EMG biofeedback training effectively reduced headache activity: 51.7% of subjects who received relaxation/biofeedback therapy recorded at least a 50% reduction in headache activity following treatment, while controls failed to improve on any measure. Improvements in headache activity in treated subjects were correlated with increases in self-efficacy induced by biofeedback training but not with changes in EMG activity or in ES2 durations. These results provide additional support for the hypothesis that cognitive changes underlie the effectiveness of relaxation and biofeedback therapies, at least in young adult tension-type headache sufferers.     

Biochemical changes associated with thermal biofeedback treatment of hypertension

Fifty-two hypertensive patients whose blood pressure (BP) was controlled on two medications received either 16 sessions of thermal biofeedback (n=30) for hand warming or 8 sessions of progressive muscle relaxation (n=22) prior to medication withdrawal. A number of biochemical measures, including plasma norepinephrine (NEPI) (supine and standing), plasma renin activity, plasma aldosterone, and urinary sodium and potassium, were taken before treatment and after treatment while medication remained constant. Results for the biofeedback-treated patients showed significant reductions in mean arterial pressure as well as in both supine and standing NEPI, while the other biochemical measures were unchanged. There were no significant changes on any variable for the relaxation-treated patients. Although the group data support a reduction in peripheral sympathetic tone as associated with the decrease in BP for the thermal biofeedback condition, dose-response relations were not significant.This research was supported by a grant from NHLBI, HL-27622.     

Role of Mood in Outcome of Biofeedback Assisted Relaxation Therapy in Insulin Dependent Diabetes Mellitus

Stressful life events and negative mood have been associated with elevated blood glucose and poor self-care in individuals with diabetes. The purpose of this controlled study was to determine the effect of mood state, specifically depression, anxiety, and daily hassles on the outcome of biofeedback assisted relaxation in insulin dependent diabetes mellitus. Eighteen subjects completed the study, nine in biofeedback assisted relaxation and nine in the control group. There were no significant group differences in blood glucose between those receiving biofeedback assisted relaxation and the subjects continuing usual care. Five of the nine experimental subjects and one of the nine control subjects were identified as succeeders according to an arbitrary criterion. Treatment failures were more depressed, more anxious, and took longer to complete the protocol than succeeders. Statistically significant correlations were found between high scores on inventories measuring depression, anxiety, and hassles intensity and higher blood glucose levels and smaller changes in blood glucose as a result of treatment. It is suggested that mood has an important impact on the response to biofeedback assisted relaxation. Further research is necessary to determine whether assessment of anxiety and depression followed by appropriate treatment where necessary should precede biofeedback assisted relaxation in insulin dependent diabetes.     

Reaction of Toxic Bicyclic Phosphates with Acetylcholinesterases and α-Chymotrypsin

Some toxic bicyclic phosphates (BPs) inhibited acetylcholinesterases (AChEs), but the activity was very weak. Even the most potent inhibitor, 4-nitro BP, inhibited bovine erythrocyte and housefly head AChEs by only 37 and 38 per cent, respectively, at 1.5 mm. Kinetic analysis indicated that the poor inhibitory activity of 4-nitro BP is ascribed not only to the low affinity for AChEs but also to its poor phosphorylating ability. Similar findings were obtained in the case of the reaction of BPs with the serine enzyme α-chymotrypsin. Despite the relatively high reactivity in an alkaline solution, BPs are much less active than other bioactive organophosphorus esters in phosphorylating a general-base-catalyzed hydroxyl group. This fact suggests that the toxic action of BPs does not result from the phosphorylation of a critical site in biological systems.     

Evaluation of a minimal-therapist-contact thermal biofeedback treatment program for essential hypertension

We compared a clinic-based regimen of 16 individual sessions (2 per week) of thermal biofeedback with a largely home-based regimen of 5 sessions (spread over 8 weeks) for the treatment of essential hypertension in patients who required at least two drugs to maintain control of blood pressure (BP). On the basis of the clinical end point of being successfully withdrawn from the second stage medication while BP remained under control, the clinic-based regimen (5 of 9) was superior (X<(1)=4.0,p<.05) to the home-based regimen (1 of 9). Internal analyses point to more frequently obtaining a hand temperature of at least 95° F by the office-based patients as possibly the reason for the difference.This research was supported by a grant from NHLBI, HL-27622.     

Respiratory Sinus Arrhythmia Versus Neck/Trapezius EMG and Incentive Inspirometry Biofeedback for Asthma: A Pilot Study

This pilot study compared biofeedback to increase respiratory sinus arrhythmia (RSA) with EMG and incentive inspirometry biofeedback in asthmatic adults. A three-group design (Waiting List Control n = 5, RSA biofeedback n = 6, and EMG biofeedback n = 6) was used. Six sessions of training were given in each of the biofeedback groups. In each of three testing sessions, five min. of respiratory resistance and EKG were obtained before and after a 20-min biofeedback session. Additional five-min epochs of data were collected at the beginning and end of the biofeedback period (or, in the control group, self-relaxation). Decreases in respiratory impedance occurred only in the RSA biofeedback group. Traub-Hering-Mayer (THM) waves (.03-.12 Hz) in heart period increased significantly in amplitude during RSA biofeedback. Subjects did not report significantly more relaxation during EMG or RSA biofeedback than during the control condition. However, decreases in pulmonary impedance, across groups, were associated with increases in relaxation. The results are consistent with Vaschillo's theory that RSA biofeedback exercises homeostatic autonomic reflex mechanisms through increasing the amplitude of cardiac oscillations. However, deep breathing during RSA biofeedback is a possible alternate explanation.     

Prevalence and Clinical Characteristics of Isolated-Office and True Resistant Hypertension Determined by Ambulatory Blood Pressure Monitoring

Hypertension is defined as resistant to treatment when a therapeutic plan including ≥3 hypertension medications failed to sufficiently lower systolic (SBP) and diastolic (DBP) blood pressures (BPs). Most individuals, including those under hypertension therapy, show a “white-coat” effect that could cause an overestimation of their real BP. The prevalence and clinical characteristics of “white-coat” or isolated-office resistant hypertension (RH) has always been evaluated by comparing clinic BP values with either daytime home BP measurements or the awake BP mean obtained from ambulatory monitoring (ABPM), therefore including patients with either normal or elevated asleep BP mean. Here, we investigated the impact of including asleep BP mean as a requirement for the definition of hypertension on the prevalence, clinical characteristics, and estimated cardiovascular (CVD) risk of isolated-office RH. This cross-sectional study evaluated 3042 patients treated with ≥3 hypertension medications and evaluated by 48-h ABPM (1707 men/1335 women), 64.2?±?11.6 (mean?±?SD) yrs of age, enrolled in the Hygia Project. Among the participants, 522 (17.2%) had true isolated-office RH (elevated clinic BP and controlled awake and asleep ambulatory BPs while treated with 3 hypertension medications), 260 (8.6%) had false isolated-office RH (elevated clinic BP, controlled awake SBP/DBP means, but elevated asleep SBP or DBP mean while treated with 3 hypertension medications), and the remaining 2260 (74.3%) had true RH (elevated awake or asleep SBP/DBP means while treated with 3 medications, or any patient treated with ≥4 medications). Patients with false, relative to those with true, isolated-office RH had higher prevalence of microalbuminuria and chronic kidney disease (CKD), significantly higher albumin/creatinine ratio (p <?.001), significantly higher 48-h SBP/DBP means by 9.6/5.3?mm Hg (p?<?.001), significantly lower sleep-time relative SBP and DBP decline (p?<?.001), and significantly greater prevalence of a non-dipper BP profile (96.9% vs. 38.9%; p?<?.001). Additionally, the prevalence of the riser BP pattern, which is associated with highest CVD risk, was much greater, 40.4% vs. 5.0% (p?<?.001), among patients with false isolated-office RH. The estimated hazard ratio of CVD events, using a fully adjusted model including the significant confounding variables of sex, age, diabetes, chronic kidney disease, asleep SBP mean, and sleep-time relative SBP decline, was significantly greater for patients with false compared with those with true isolated-office RH (2.13 [95% confidence interval: 1.95–2.32]; p?<?.001). Patients with false isolated-office hypertension and true RH, however, were equivalent for the prevalence of obstructive sleep apnea, metabolic syndrome, obesity, diabetes, microalbuminuria, and chronic kidney disease, and they had an equivalent estimated hazard ratio of CVD events (1.04 [95% confidence interval: .97–1.12]; p?=?.265). Our findings document a significantly elevated prevalence of a blunted nighttime BP decline in patients here categorized as either false isolated-office RH and true RH, jointly accounting for 82.8% of the studied sample. Previous reports of much lower prevalence of true RH plus a nonsignificant increased CVD risk of this condition compared with isolated-office RH are misleading by disregarding asleep BP mean for classification. Our results further indicate that classification of RH patients into categories of isolated-office RH, masked RH, and true RH cannot be based on the comparison of clinic BP with either daytime home BP measurements or awake BP mean from ABPM, as so far customary in the available literature, totally disregarding the highly significant prognostic value of nighttime BP. Accordingly, ABPM should be regarded as a clinical requirement for proper diagnosis of true RH. (Author correspondence: rhermida@uvigo.es)     

Biochemical changes associated with thermal biofeedback treatment of hypertension

Fifty-two hypertensive patients whose blood pressure (BP) was controlled on two medications received either 16 sessions of thermal biofeedback (n = 30) for hand warming or 8 sessions of progressive muscle relaxation (n = 22) prior to medication withdrawal. A number of biochemical measures, including plasma norepinephrine (NEPI) (supine and standing), plasma renin activity, plasma aldosterone, and urinary sodium and potassium, were taken before treatment and after treatment while medication remained constant. Results for the biofeedback-treated patients showed significant reductions in mean arterial pressure as well as in both supine and standing NEPI, while the other biochemical measures were unchanged. There were no significant changes on any variable for the relaxation-treated patients. Although the group data support a reduction in peripheral sympathetic tone as associated with the decrease in BP for the thermal biofeedback condition, dose-response relations were not significant.     

Molecular cloning and expression patterns of FK506‐binding protein 12, an immunophilin from the cabbage butterfly,Pieris rapae

FK506‐binding protein (FK506BP) class belonging to immunophilin protein family has been known to play key roles in modulating T‐cell activation, regulation of cell cycle and protein folding. However, little is known about the involvement of FK506BP during viral pathogenesis in insect host. In this study, an attempt has been made to focus on the involvement of FK506BP in antiviral innate immunity, by cloning the full‐length cDNA of FK506BP12 (PrFK506BP12) from the cabbage butterfly, Pieris rapae. It comprised of 532 bp (excluding poly‐A tail) with a longest open reading frame (ORF) of 327 bp encoding 108 amino acids. In silico analysis of PrFK506BP12 ORF revealed a highly conserved FK506‐binding domain (FKBD). As expected, it showed high homology to other FK506BPs identified from Bombyx mori (92%), Manduca sexta (91%), Suberites domuncula (82%), Tribolium castaneum (81%) and Aedes aegypti (74%) . Expression of PrFK506BP12 was observed during developmental stages of P. rapae, but was pronounced in late pupal and adult stage. In addition, spatial expression pattern analysis indicated its high expression in the head and fat body. Furthermore, PrFK506BP12 mRNA was induced 12 h after LTA, Poly I:C treatment and 3h after Pieris rapae granulovirus (PrGV) treatment in carcass. It suggests that PrFK506BP12 appears to be involved in immune responses and also play an important role in the fat body, although it remains to be clarified about their precise role in response to granulovirus.     

Risk of Severe Upper Gastrointestinal Complications among Oral Bisphosphonate Users

Background

Oral bisphosphonates (BPs) are the primary agents for the treatment of osteoporosis. Although BPs are generally well tolerated, serious gastrointestinal adverse events have been observed.

Aim

To assess the risk of severe upper gastrointestinal complications (UGIC) among BP users by means of a large study based on a network of Italian healthcare utilization databases.

Methods

A nested case-control study was carried out by including 110,220 patients aged 45 years or older who, from 2003 until 2005, were treated with oral BPs. Cases were the 862 patients who experienced the outcome (hospitalization for UGIC) until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio (OR) associated with current use of BPs after adjusting for several covariates. A set of sensitivity analyses was performed in order to account for sources of systematic uncertainty.

Results

The adjusted OR for current use of BPs with respect to past use was 0.94 (95% CI 0.81 to 1.08). There was no evidence that this risk changed either with BP type and regimen, or concurrent use of other drugs or previous hospitalizations.

Conclusions

No evidence was found that current use of BPs increases the risk of severe upper gastrointestinal complications compared to past use.     

EMG biofeedback treatment of torticollis: a controlled outcome study.

Successful treatment of torticollis with electromyographic (EMG) biofeedback has been reported in a number of single case and single group studies. The present investigation represents the first controlled outcome study. Twelve torticollis patients were randomly assigned to EMG biofeedback or relaxation training and graded neck exercises (RGP). The procedure involved three sessions of baseline assessment, 15 sessions of EMG BF or RGP, 6 sessions of EMG BF or RGP plus home-management, 6 sessions of home-management alone, and follow-up 3 months after the end of treatment. A variety of outcome measures were used including physiological (EMG from the two sternocleidomastoid muscles, skin conductance level), behavioral (angle of head deviation, range of movement of the head), and self-report (depression, functional disability, body concept), therapist and "significant other" reports and independent observer assessment of videos. In both groups, neck muscle activity was reduced from pre- to posttreatment. This reduction was greater in the EMG biofeedback group. There was evidence of feedback-specific neck muscle relaxation in the EMG biofeedback group. Therefore, the outcome was not due to nonspecific factors and could be attributed to feedback-specific effects. Changes in skin conductance level showed that neck muscle relaxation was not simply mediated by a general reduction of "arousal." Significant improvements of extent of head deviation, and range of movement of the head, as well as reductions of depression were present, which were not different in the two groups. At the end of treatment, no patient was asymptomatic. Any therapeutic benefit was generally maintained at follow-up. The results and the procedural simplicity of RGP make the issue of cost-efficacy of EMG biofeedback a pertinent one. Further controlled outcome studies of EMG biofeedback treatment of torticollis with larger samples are required.     

Interaction of biofeedback-assisted relaxation and diuretic in treatment of essential hypertension

Thirty patients with essential hypertension participated in a study designed to compare two treatments: diuretic medication alone (n=10) and biofeedback assisted relaxation combined with diuretic (n=20). One of 10 patients lowered BP with diuretic alone and 11 of 20 patients lowered BP with diuretic combined with biofeedback-assisted relaxation. The addition of the behavioral intervention to the diuretic therapy produced a decrease in blood pressure beyond that associated with the diuretic alone. The decreases in BP mediated by diuretic were related to high entry levels of BP, low anxiety, forehead muscle tension, anger expression and plasma renin activity. The BP decrease mediated by combined diuretic and biofeedback-assisted relaxation was associated with high pretreatment BP, anger controlled, low finger temperature and high/normal plasma renin activity.This work supported by the Northwestern Ohio Heart Association under grant No. 93132 to Dr. McGrady.     

Interaction of biofeedback-assisted relaxation and diuretic in treatment of essential hypertension.

Thirty patients with essential hypertension participated in a study designed to compare two treatments: diuretic medication alone (n = 10) and biofeedback assisted relaxation combined with diuretic (n = 20). One of 10 patients lowered BP with diuretic alone and 11 of 20 patients lowered BP with diuretic combined with biofeedback-assisted relaxation. The addition of the behavioral intervention to the diuretic therapy produced a decrease in blood pressure beyond that associated with the diuretic alone. The decrease in BP mediated by diuretic were related to high entry levels of BP, low anxiety, forehead muscle tension, anger expression and plasma renin activity. The BP decrease mediated by combined diuretic and biofeedback-assisted relaxation was associated with high pretreatment BP, anger controlled, low finger temperature and high/normal plasma renin activity.     

An incremental model to isolate specific effects of behavioral treatments in essential hypertension

To prove clinical effectiveness of behavioral treatments in essential hypertension, an incremental repeated measures design was combined with findings that positive expectancies (placebo factors) potentiate specific effects. If positive expectancy effects were maximized in a Baseline Control Phase (6–26 weeks of BP stabilization), specific effects might be isolated as well as potentiated in a Learning Phase (2a, 6 weeks, twice/week; 2b, 6 weeks, once/week—fading). Follow-up Phase 3 was six weeks, once/week; six months, once/month; and at 12 months. To equalize groups across seasons over 12 years of regular clinical work, 117 volunteer outpatient veterans with borderline to moderate essential hypertension (130–170/90–110) were assigned in order of entry (10–20 each year) to one of four Treatments: R, simple relaxation; REMG, R + EMG biofeedback; BP, BP biofeedback only; RBP, R + BP; or to an inert Control Group (TA, reading about transactional analysis without skills training). The four treatment groups showed modest but consistent BP decreases during Phase 2 (p range from .0001 to .01). Control Phase placebo effects matched those in the Control Group (no BP decrease after Baseline). With a two-way mixed ANOVA design, Learning Phase 2 isolated specific effects of behavioral treatments, while the Control Phase 1 with liberal placebo factors potentiated specific effects during regular clinical work.This research was supported in part by NIH Research grant No. R01-HL27220; by the Hypertension Investigation Pooled Project of the National Heart, Lung and Blood Institute of NIH; and by the VA Medical Research, Va Hines Hospital, Hines, Illinois. The contributions of the following Medical and Nursing staff members are gratefully acknowledged: Javier Clemente, David Weber, Peter Kraut, Ali Kheirbek, David Leehey, Alan Reich, Gloria Lorenz, Della Herzog, Geraldine Stroka.     

EMG biofeedback treatment of torticollis: A controlled outcome study

Successful treatment of torticollis with electromyographic (EMG) biofeedback has been reported in a number of single case and single group studies. The present investigation represents the first controlled outcome study. Twelve torticollis patients were randomly assigned to EMG biofeedback or relaxation training and graded neck exercises (RGP). The procedure involved three sessions of baseline assessment, 15 sessions of EMG BF or RGP, 6 sessions of EMG BF or RGP plus home-management, 6 sessions of home-management alone, and follow-up 3 months after the end of treatment. A variety of outcome measures were used including physiological (EMG from the two sternocleidomastoid muscles, skin conductance level), behavioral (angle of head deviation, range of movement of the head), and self-report (depression, functional disability, body concept), therapist and significant other reports and independent observer assessment of videos. In both groups, neck muscle activity was reduced from pre- to posttreatment. This reduction was greater in the EMG biofeedback group. There was evidence of feedback-specific neck muscle relaxation in the EMG biofeedback group. Therefore, the outcome was not due to nonspecific factors and could be attributed to feedback-specific effects. Changes in skin conductance level showed that neck muscle relaxation was not simply mediated by a general reduction of arousal. Significant improvements of extent of head deviation, and range of movement of the head, as well as reductions of depression were present, which were not different in the two groups. At the end of treatment, no patient was asymptomatic. Any therapeutic benefit was generally maintained at follow-up. The results and the procedural simplicity of RGP make the issue of cost-efficacy of EMG biofeedback a pertinent one. Further controlled outcome studies of EMG biofeedback treatment of torticollis with larger samples are required.This work was funded by grants from the Medical Research Council and the Dystonia Society.     

Binding Pockets and Permeation Channels for Dioxygen through Cofactorless 3‐Hydroxy‐2‐methylquinolin‐4‐one 2,4‐Dioxygenase in Association with Its Natural Substrate, 3‐Hydroxy‐2‐methylquinolin‐4(1H)‐one. A Perspective from Molecular Dynamics Simulations

This work describes an investigation of pathways and binging pockets (BPs) for dioxygen (O₂) through the cofactorless oxygenase 3‐hydroxy‐2‐methylquinolin‐4‐one 2,4‐dioxygenase in complex with its natural substrate, 3‐hydroxy‐2‐methylquinolin‐4(1H)‐one, in aqueous solution. The investigation tool was random‐acceleration molecular dynamics (RAMD), whereby a tiny, randomly oriented external force is applied to O₂ in order to accelerate its movements. In doing that, care was taken that the external force only continues, if O₂ moves along a direction for a given period of time, otherwise the force changed direction randomly. Gates for expulsion of O₂ from the protein, which can also be taken as gates for O₂ uptake, were found throughout almost the whole external surface of the protein, alongside a variety of BPs for O₂. The most exploited gates and BPs were not found to correspond to the single gate and BP proposed previously from the examination of the static model from X‐ray diffraction analysis of this system. Therefore, experimental investigations of this system that go beyond the static model are urgently needed.