Taiji practice attenuates psychobiological stress reactivity - A randomized controlled trial in healthy subjects

Background: Stress reducing effects of Taiji, a mindful and gentle form of body movement, have been reported in previous studies, but standardized and controlled experimental studies are scarce. The present study investigates the effect of regular Taiji practice on psychobiological stress response in healthy men and women. Methods: 70 participants were randomly assigned to either Taiji classes or a waiting list. After 3 months, 26 (8 men, 18 women) persons in the Taiji group and 23 (9 men, 14 women) in the waiting control group underwent a standardized psychosocial stress test combining public speaking and mental arithmetic in front of an audience. Salivary cortisol and α-amylase, heart rate, and psychological responses to psychosocial stress were compared between the study groups. (ClinicalTrials.gov number, NCT01122706.) Results: Stress induced characteristic changes in all psychological and physiological measures. Compared to controls, Taiji participants exhibited a significantly lower stress reactivity of cortisol (p = .028) and heart rate (p = .028), as well as lower α-amylase levels (p = .049). They reported a lower increase in perceived stressfulness (p = .006) and maintained a higher level of calmness (p = .019) in response to psychosocial stress. Conclusion: Our results consistently suggest that practicing Taiji attenuates psychobiological stress reactivity in healthy subjects. This may underline the role of Taiji as a useful mind–body practice for stress prevention.

A pilot study to evaluate the success and survival rate of titanium-zirconium implants in partially edentulous patients: results after 24 months of follow-up

Implants made from a new titanium-zirconium (TiZr) alloy (Roxolid) have shown good osseointegration with no adverse effects in animal studies. This single-cohort pilot study was performed to evaluate the performance and safe use of reduced-diameter implants made from this new TiZr alloy for the first time in human subjects, in a prospective case-controlled series.

Five-year results of a randomized controlled clinical trial comparing zirconia and titanium abutments supporting single-implant crowns in canine and posterior regions

OBJECTIVES: To test the survival rates, and the technical and biological complication rates of customized zirconia and titanium abutments 5 years after crown insertion. MATERIAL AND METHODS: Twenty-two patients with 40 single implants in maxillary and mandibular canine and posterior regions were included. The implant sites were randomly assigned to zirconia abutments supporting all-ceramic crowns or titanium abutments supporting metal-ceramic crowns. Clinical examinations were performed at baseline, and at 6, 12, 36 and 60 months of follow-up. The abutments and reconstructions were examined for technical and/or biological complications. Probing pocket depth (PPD), plaque control record (PCR) and Bleeding on Probing (BOP) were assessed at abutments (test) and analogous contralateral teeth (control). Radiographs of the implants revealed the bone level (BL) on mesial (mBL) and distal sides (dBL). Data were statistically analyzed with nonparametric mixed models provided by Brunner and Langer and STATA (P < 0.05). RESULTS: Eighteen patients with 18 zirconia and 10 titanium abutments were available at a mean follow-up of 5.6 years (range 4.5-6.3 years). No abutment fracture or loss of a reconstruction occurred. Hence, the survival rate was 100% for both. Survival of implants supporting zirconia abutments was 88.9% and 90% for implants supporting titanium abutments. Chipping of the veneering ceramic occurred at three metal-ceramic crowns supported by titanium abutments. No significant differences were found at the zirconia and titanium abutments for PPD (meanPPD(ZrO2) 3.3 ± 0.6 mm, mPPD(T) (i) 3.6 ± 1.1 mm), PCR (mPCR(Z) (rO) (2) 0.1 ± 0.3, mPCR(T) (i) 0.3 ± 0.2) and BOP (mBOP(Z) (rO) (2) 0.5 ± 0.3, mBOP(T) (i) 0.6 ± 0.3). Moreover, the BL was similar at implants supporting zirconia and titanium abutments (mBL(Z) (rO) (2) 1.8 ± 0.5, dBL(Z) (rO) (2) 2.0 ± 0.8; mBL(T) (i) 2.0 ± 0.8, dBL(T) (i) 1.9 ± 0.8). CONCLUSIONS: There were no statistically or clinically relevant differences between the 5-year survival rates, and the technical and biological complication rates of zirconia and titanium abutments in posterior regions.

Antinociceptive activity of pre- versus post-operative intra-articular bupivacaine in goats undergoing stifle arthrotomy

OBJECTIVE: To evaluate the peri-operative analgesic efficacy of intra-articular bupivacaine administered before or after stifle arthrotomy. STUDY DESIGN: Prospective, randomized, blind, placebo-controlled experimental trial. ANIMALS: Thirty-nine healthy goats. METHODS: The goats were allocated randomly to one of three intra-articular treatment groups: group PRE (bupivacaine before and saline after surgery), group POST (saline before and bupivacaine after surgery) and group CON (saline before and after surgery). Anaesthesia was maintained with a constant end-tidal sevoflurane of 2.5%. Intra-operatively heart rate (HR), respiratory rate and mean arterial blood pressure (MAP) after critical surgical events (CSE) were recorded and compared with pre-incision values. Propofol requirements to maintain surgical anaesthesia were recorded. Flunixin was administered for 5 days. Post-operative pain assessment at 20 minutes, 2 hours, 4 hours after recovery and on day 2 and 3 included a multidimensional pain score (MPS), a lameness score and mechanical nociceptive threshold (MNT) testing. Rescue analgesia consisted of systemic opioids. Data were analysed using Kruskal-Wallis, Mann-Whitney, Friedman or chi-square tests as appropriate. RESULTS: Intra-operatively, group PRE had lower HR and MAP at several CSEs than groups POST/CON and required less propofol [0 mg kg(-1) (0-0 mg kg(-1))] than group POST/CON [0.3 mg kg(-1) (0-0.6 mg kg(-1))]. Post-operatively, group POST had significantly higher peri-articular MNTs than groups PRE and CON up to 4 hours after recovery. No treatment effect was detected for MPS, lameness scores and rescue analgesic consumption at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: Pre-operative intra-articular bupivacaine provided notable intra-operative analgesia in goats undergoing stifle arthrotomy but did not reduce post-operative pain. Post-operative intra-articular bupivacaine provided a short lasting reduction of peri-articular hyperalgesia without affecting the requirements for systemic analgesia. Multimodal perioperative pain therapy is recommended to provide adequate analgesia for stifle arthrotomy in goats.

The Effects of Pi-Pi Stacking on the Controlled Radical Polymerization of Vinyl Aromatics

The atom transfer radical polymerization (ATRP) of styrene (St) was conducted in the presence of varying equivalence (eq) of hexafluorobenzene (HFB) and octafluorotoluene (OFT) to probe the effects of pi-pi stacking on the rate of the polymerization and on the tacticity of the resulting polystyrene (PSt). The extent of the pi-pi stacking interaction between HFB/OFT and the terminal polystyrenic phenyl group was also investigated as a function of solvent, both non-aromatic solvents (THF and hexanes) and aromatic solvents (benzene and toluene). In all cases the presence of HFB or OFT resulted in a decrease in monomer conversion indicating a reduction in the rate of the polymerization with greater retardation of the rate with increase eq of HFB or OFT (0.5 eq to 1 eq HFB/OFT compared to St). Additionally, when aromatic solvents were used instead of non-aromatic solvents the effect of the HFB/OFT on the rate was minimized, consistent with the aromatic solvent competitively interacting with the HFB/OFT. The effects of temperature and ligand strength on the ATRP of St in the presence of HFB were also probed. It was found that when using N,N,N’,N’,N’’-pentamethyldiethylenetriamine (PMDETA) as the ligand the effects of HFB at 38o were the same as at 86oC. When tris[2-(dimethylamino)ethyl]-amine (Me6TREN) was used as the ligand at 38o there was a decrease in monomer conversion similar to the analogous PMDETA reaction. When the polymerization was conducted at 86oC there was no effect on the monomer conversion with HFB present compared to when HFB was absent. To investigate the pi-pi stacking effect even further, the reverse pi-pi stacking system was observed by conducting the ATRP of pentafluorostyrene (PFSt) in the presence of varying eq of benzene and toluene, which in both cases resulted in an increase in monomer conversion compared to when benzene or toluene were absent; in summary the rate of the ATRP of PFSt increases when benzene or toluene waas present in the reaction. The pi-pi stacking interaction between the HFB/OFT and the dormant alkyl bromide of the polymer chain was verified by 1H-NMR with 1-bromoethylbenzene as the alkyl bromide. Also verified by 1H-NMR was the interaction between HFB/OFT and St and the interaction between PFSt and benzene. In all 1H-NMR spectra a perturbation in the aromatic and/or vinyl peaks was observed when the pi-pi stacking agent was present compared to when it was absent. The tacticity of the PSt formed in the presence of 1 eq of HFB was compared to the PSt formed in the absence of HFB by observing the C1 signal in their 13C-NMR spectra, but no change in shape or chemical shift of the signal was observed indicating that there was no change in tacticity.

Duloxetine inhibits effects of MDMA ("ecstasy") in vitro and in humans in a randomized placebo-controlled laboratory study

This study assessed the effects of the serotonin (5-HT) and norepinephrine (NE) transporter inhibitor duloxetine on the effects of 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy) in vitro and in 16 healthy subjects. The clinical study used a double-blind, randomized, placebo-controlled, four-session, crossover design. In vitro, duloxetine blocked the release of both 5-HT and NE by MDMA or by its metabolite 3,4-methylenedioxyamphetamine from transmitter-loaded human cells expressing the 5-HT or NE transporter. In humans, duloxetine inhibited the effects of MDMA including elevations in circulating NE, increases in blood pressure and heart rate, and the subjective drug effects. Duloxetine inhibited the pharmacodynamic response to MDMA despite an increase in duloxetine-associated elevations in plasma MDMA levels. The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA. Duloxetine may be useful in the treatment of psychostimulant dependence.

Impact of del32-71-GH (exon 3 skipped GH) on intracellular GH distribution, secretion and cell viability: a quantitative confocal microscopy analysis

BACKGROUND: Familial isolated growth hormone deficiency (IGHD) is a disorder with about 5-30% of patients having affected relatives. Among those familial types, IGHD type II is an autosomal dominant form of short stature, associated in some families with mutations that result in missplicing to produce del32-71-GH, a GH peptide which cannot fold properly. The mechanism by which this mutant GH may alter the controlled secretory pathway and therefore suppress the secretion of the normal 22-kDa GH product of the normal allele is not known in detail. Previous studies have shown variance depending on cell type, transfection technique used, as well as on the method of analysis performed. AIM: The aim of our study was to analyse and compare the subcellular distribution/localization of del32-71-GH or wild-type (wt)-GH (22-kDa GH), each stably transfected into AtT-20, a mouse pituitary cell line endogenously producing ACTH, employed as the internal control for secretion assessment. METHODS: Colocalization of wt- and del32-71 mutant GH form was studied by quantitative confocal microscopy analysis. Using the immunofluorescent technique, cells were double stained for GH plus one of the following organelles: endoplasmic reticulum (ER anti-Grp94), Golgi (anti-betaCOP) or secretory granules (anti-Rab3a). In addition, GH secretion and cell viability were analysed in detail. RESULTS/CONCLUSIONS: Our results show that in AtT-20 neuroendocrine cells, in comparison to the wt-GH, the del32-71-GH has a major impact on the secretory pathway not only affecting GH but also other peptides such as ACTH. The del32-71-GH is still present at the secretory vesicles' level, albeit in reduced quantity when compared to wt-GH but, importantly, was secretion-deficient. Furthermore, while focusing on cell viability an additional finding presented that the various splice site mutations, even though leading eventually to the same end product, namely del32-71-GH, have different and specific consequences on cell viability and proliferation rate.

A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints

Publication bias and related bias in meta-analysis is often examined by visually checking for asymmetry in funnel plots of treatment effect against its standard error. Formal statistical tests of funnel plot asymmetry have been proposed, but when applied to binary outcome data these can give false-positive rates that are higher than the nominal level in some situations (large treatment effects, or few events per trial, or all trials of similar sizes). We develop a modified linear regression test for funnel plot asymmetry based on the efficient score and its variance, Fisher's information. The performance of this test is compared to the other proposed tests in simulation analyses based on the characteristics of published controlled trials. When there is little or no between-trial heterogeneity, this modified test has a false-positive rate close to the nominal level while maintaining similar power to the original linear regression test ('Egger' test). When the degree of between-trial heterogeneity is large, none of the tests that have been proposed has uniformly good properties.

Maintenance of end-expiratory recruitment with increased respiratory rate after saline-lavage lung injury

Cyclical recruitment of atelectasis with each breath is thought to contribute to ventilator-associated lung injury. Extrinsic positive end-expiratory pressure (PEEPe) can maintain alveolar recruitment at end exhalation, but PEEPe depresses cardiac output and increases overdistension. Short exhalation times can also maintain end-expiratory recruitment, but if the mechanism of this recruitment is generation of intrinsic PEEP (PEEPi), there would be little advantage compared with PEEPe. In seven New Zealand White rabbits, we compared recruitment from increased respiratory rate (RR) to recruitment from increased PEEPe after saline lavage. Rabbits were ventilated in pressure control mode with a fraction of inspired O(2) (Fi(O(2))) of 1.0, inspiratory-to-expiratory ratio of 2:1, and plateau pressure of 28 cmH(2)O, and either 1) high RR (24) and low PEEPe (3.5) or 2) low RR (7) and high PEEPe (14). We assessed cyclical lung recruitment with a fast arterial Po(2) probe, and we assessed average recruitment with blood gas data. We measured PEEPi, cardiac output, and mixed venous saturation at each ventilator setting. Recruitment achieved by increased RR and short exhalation time was nearly equivalent to recruitment achieved by increased PEEPe. The short exhalation time at increased RR, however, did not generate PEEPi. Cardiac output was increased on average 13% in the high RR group compared with the high PEEPe group (P < 0.001), and mixed venous saturation was consistently greater in the high RR group (P < 0.001). Prevention of end-expiratory derecruitment without increased end-expiratory pressure suggests that another mechanism, distinct from intrinsic PEEP, plays a role in the dynamic behavior of atelectasis.

Model-based control of neuromuscular block using mivacurium: design and clinical verification

BACKGROUND: Short-acting agents for neuromuscular block (NMB) require frequent dosing adjustments for individual patient's needs. In this study, we verified a new closed-loop controller for mivacurium dosing in clinical trials. METHODS: Fifteen patients were studied. T1% measured with electromyography was used as input signal for the model-based controller. After induction of propofol/opiate anaesthesia, stabilization of baseline electromyography signal was awaited and a bolus of 0.3 mg kg-1 mivacurium was then administered to facilitate endotracheal intubation. Closed-loop infusion was started thereafter, targeting a neuromuscular block of 90%. Setpoint deviation, the number of manual interventions and surgeon's complaints were recorded. Drug use and its variability between and within patients were evaluated. RESULTS: Median time of closed-loop control for the 11 patients included in the data processing was 135 [89-336] min (median [range]). Four patients had to be excluded because of sensor problems. Mean absolute deviation from setpoint was 1.8 +/- 0.9 T1%. Neither manual interventions nor complaints from the surgeons were recorded. Mean necessary mivacurium infusion rate was 7.0 +/- 2.2 microg kg-1 min-1. Intrapatient variability of mean infusion rates over 30-min interval showed high differences up to a factor of 1.8 between highest and lowest requirement in the same patient. CONCLUSIONS: Neuromuscular block can precisely be controlled with mivacurium using our model-based controller. The amount of mivacurium needed to maintain T1% at defined constant levels differed largely between and within patients. Closed-loop control seems therefore advantageous to automatically maintain neuromuscular block at constant levels.

Neoadjuvant interstitial high-dose-rate (HDR) brachytherapy combined with systemic chemotherapy in patients with breast cancer

BACKGROUND AND PURPOSE: This is the first study investigating neoadjuvant interstitial high-dose-rate (HDR) brachytherapy combined with chemotherapy in patients with breast cancer. The goal was to evaluate the type of surgical treatment, histopathologic response, side effects, local control, and survival. PATIENTS AND METHODS: 53 patients, who could not be treated with breast-conserving surgery due to initial tumor size (36/53) or due to an unfavorable breast-tumor ratio (17/53), were analyzed retrospectively. All but one were in an intermediate/high-risk group (St. Gallen criteria). The patients received a neoadjuvant protocol consisting of systemic chemotherapy combined with fractionated HDR brachytherapy (2 x 5 Gy/day, total dose 30 Gy). In cases, where breast-conserving surgery was performed, patients received additional external-beam radiotherapy (EBRT, 1.8 Gy/day, total dose 50.4 Gy). In patients, who underwent mastectomy but showed an initial tumor size of T3/T4 and/or more than three infiltrated lymph nodes, EBRT was also performed. RESULTS: In 30/53 patients (56.6%) breast-conserving surgery could be performed. The overall histopathologic response rate was 96.2% with a complete remission in 28.3% of patients. 49/53 patients were evaluable for follow-up. After a median of 58 months (45-72 months), one patient showed a mild fibrosis of the breast tissue, three patients had mild to moderate lymphatic edema of the arm. 6/49 (12.2%) patients died of distant metastases, 4/49 (8.2%) were alive with disease, and 39/49 (79.6%) were free from disease. Local recurrence was observed in only one case (2%) 40 months after primary therapy. After mastectomy, this patient is currently free from disease. CONCLUSION: The combination of interstitial HDR brachytherapy and chemotherapy is a well-tolerated and effective neoadjuvant treatment in patients with breast cancer. Compared to EBRT, treatment time is short. Postoperative EBRT of the whole breast -- if necessary -- is still possible after neoadjuvant brachytherapy. Even though the number of patients does not permit definite conclusions, the results are promising regarding survival and the very low rate of local recurrences.

Levocetirizine is an effective treatment in patients suffering from chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled, parallel, multicenter study

BACKGROUND: Chronic idiopathic urticaria (CIU) is defined by the almost daily presence of urticaria for at least 6 weeks without an identifiable cause. Symptoms include short-lived wheals, itching, and erythema. CIU impedes significantly a patient's quality of life (QoL). Levocetirizine is an antihistamine from the latest generation approved for CIU. AIM: To investigate the efficacy of levocetirizine, 5 mg, and placebo for the symptoms and signs of CIU, as well as for the QoL and productivity. METHODS: The primary criteria of evaluation were the pruritus severity scores over 1 week of treatment and over 4 weeks. The QoL was assessed via the Dermatology Life Quality Index (DLQI). RESULTS: Baseline pruritus severity scores were comparable in the two treatment groups (2.06+/-0.58). After 1 week, levocetirizine was superior to placebo and demonstrated a considerable efficacy (difference=0.78, P<0.001). This efficacy was maintained over the entire study period (4 weeks, P<0.001). The number and size of wheals were considerably reduced compared with placebo over 1 week and over the total treatment period (P

New concept for CTO recanalization using controlled antegrade and retrograde subintimal tracking: the CART technique

OBJECTIVES: To demonstrate the safety and feasibility of a new concept for CTO recanalization using a controlled antegrade and retrograde subintimal tracking technique (CART technique). BACKGROUND: A successful percutaneous recanalization of chronic coronary occlusions results in improved survival, as well as enhanced left ventricular function, reduction in angina, and improved exercise tolerance. However, successful recanalization of CTOs is still not optimal, and needs further improvements. METHODS: Ten patients with a CTO underwent the CART procedure. This technique combines the simultaneous use of the antegrade and retrograde approaches. A subintimal dissection is created antegradely and retrogradely, which allows the operator to limit the extension of the subintimal dissection in the CTO portion. A retrograde approach means that the occlusion site is approached in a retrograde fashion through the best collateral channel from any other patent coronary artery. RESULTS: The occlusion site was located in the RCA in 9 patients, and in the LAD in 1 patient. CTO duration varied from 7 to 84 months. Vessel recanalization was achieved in all patients. In all cases, the subintimal dissection was limited to the CTO region. No complications occurred in the collateral channel used for the retrograde approach. There were no in-hospital major adverse cardiac events. CONCLUSIONS: The CART technique is feasible, safe, and has a high success rate.

Luminal substrate "brake" on mucosal maltase-glucoamylase activity regulates total rate of starch digestion to glucose

BACKGROUND: Starches are the major source of dietary glucose in weaned children and adults. However, small intestine alpha-glucogenesis by starch digestion is poorly understood due to substrate structural and chemical complexity, as well as the multiplicity of participating enzymes. Our objective was dissection of luminal and mucosal alpha-glucosidase activities participating in digestion of the soluble starch product maltodextrin (MDx). PATIENTS AND METHODS: Immunoprecipitated assays were performed on biopsy specimens and isolated enterocytes with MDx substrate. RESULTS: Mucosal sucrase-isomaltase (SI) and maltase-glucoamylase (MGAM) contributed 85% of total in vitro alpha-glucogenesis. Recombinant human pancreatic alpha-amylase alone contributed <15% of in vitro alpha-glucogenesis; however, alpha-amylase strongly amplified the mucosal alpha-glucogenic activities by preprocessing of starch to short glucose oligomer substrates. At low glucose oligomer concentrations, MGAM was 10 times more active than SI, but at higher concentrations it experienced substrate inhibition whereas SI was not affected. The in vitro results indicated that MGAM activity is inhibited by alpha-amylase digested starch product "brake" and contributes only 20% of mucosal alpha-glucogenic activity. SI contributes most of the alpha-glucogenic activity at higher oligomer substrate concentrations. CONCLUSIONS: MGAM primes and SI activity sustains and constrains prandial alpha-glucogenesis from starch oligomers at approximately 5% of the uninhibited rate. This coupled mucosal mechanism may contribute to highly efficient glucogenesis from low-starch diets and play a role in meeting the high requirement for glucose during children's brain maturation. The brake could play a constraining role on rates of glucose production from higher-starch diets consumed by an older population at risk for degenerative metabolic disorders.

Clinical outcome of a short-term psychotherapeutic intervention for the treatment of dental phobia

Objective: Anxiety before receiving dental treatment is widespread. The aim of this investigation was to evaluate the effect of a brief psychologic treatment on adherence to the dental treatment regimen in patients with dental phobia. Method and Materials: Dental phobic patients (n = 160) received 3 sessions of cognitive behavioral therapy that consisted of stress management training and exposure to phobic stimuli. The outcome was determined in terms of 3 subsequent dental visits. Results: Participating patients had not visited a dental clinician for an average of 6 years. Comparison of patients who completed the psychologic treatment with those who dropped out showed that 68% of the former but also 52% of the latter adhered to the subsequent dental treatment regimen. The number of psychologic treatment sessions correlated significantly and positively with anxiety level before treatment. Conclusion: Short-term psychologic therapy of 3 sessions results in a success rate of 70% to adherence to dental treatment among dental phobic patients. Duration of avoidance of anxiety before treatment was not related to success in completing the trial. Nevertheless, the more intense the patient's phobia, the more psychotherapeutic sessions were necessary. (Quintessence Int 2007;38; E589-E596).