Hourly effect of atmospheric reactive nitrogen species on the onset of acute ischemic stroke: Insight from the Shanghai Stroke Service System Database.

Acute ischemic stroke (AIS) is one of the most predominant causes of mortality and disability in China. Significant uncertainties in stroke diagnosis and time of onset have resulted in inconsistent evidence on the association between ambient air pollution and the risk of AIS. The present study aimed to evaluate the impact of air pollution on AIS onset based on high time-resolution air pollution data and a stroke-specific registry across the past five years. Hourly concentrations of PM2.5, PM10, O3, SO2, CO, NO2 and nitrous acid (HONO) were monitored from 2017 to 2021, with which a distributed lag non-linear model and conditional logistic regression models coupled with a time-stratified case-crossover design were applied to 106,623 AIS cases recorded in the Shanghai Stroke Service (4S) database during the study period. Results from the conditional logistic regression models indicate that acute exposure to PM2.5, PM10, SO2, NO2 and HONO was found to be associated with AIS onset, respectively. The corresponding cumulative excessive risks of AIS onset were 0.8 %, 1 %, 2.4 %, 2.1 % and 1.8 % for each interquartile range increase in the respective concentration. The longest lag-effect (up to 13 h) was observed for reactive nitrogen species (RNS), such as NO2 and HONO, which remained robust in two-pollutant models. Similar important role of RNS in AIS onset were confirmed by the distributed lag non-linear model. By demonstrating the transient effect of ambient air pollution on AIS, especially the relationships between RNS and AIS for the first time, our study provides stringent evidence for future mitigation strategies for pollution emission and public health.

Octreotide improves human lymphatic fluid transport a translational trial.

OBJECTIVES: Chylothorax is a complex condition and many different pharmacological agents have been tried as treatment. Octreotide is used off-label to treat chylothorax, but the efficacy of octreotide remains unclear. A decrease in lymph production is suggested as the mechanism. In this cross-over study, we explore the direct effect of octreotide on human lymphatic drainage. METHODS: Pre-clinical: the effect of octreotide on force generation was assessed during acute and prolonged drug incubation on human lymphatic vessels mounted in a myograph. Clinical: in a double-blinded, randomized, cross-over trial including 16 healthy adults, we administered either octreotide or saline as an intravenous infusion for 2.5 h. Near-infrared fluorescence imaging was used to examine spontaneous lymphatic contractions and lymph pressure in peripheral lymphatic vessels and plethysmography was performed to assess the capillary filtration rate, capillary filtration coefficient and isovolumetric pressures of the lower leg. RESULTS: Pre-clinical: human thoracic duct (n = 12) contraction rate was concentration-dependently stimulated by octreotide with a maximum effect at 10 and 100 nmol/l in the myograph chamber. Clinical: spontaneous lymphatic contractions and lymph pressure evaluated by near-infrared fluorescence did not differ between octreotide or placebo (P = 0.36). Plethysmography revealed similar capillary filtration coefficients (P = 0.057), but almost a doubling of the isovolumetric pressures (P = 0.005) during octreotide infusion. CONCLUSIONS: Octreotide stimulated lymphatic contractility in the pre-clinical setup but did not affect the spontaneous lymphatic contractions or lymph pressure in healthy individuals. Plethysmography revealed a doubling in the isovolumetric pressure. These results suggest that octreotide increases lymphatic drainage capacity in situations with high lymphatic afterload.

A self-controlled, cross-over study of intensive insulin treatment with needle-based injection versus needle-free injection in hospitalized patients with type 2 diabetes.

Background and Aims: Needle injection and needle-free injection were proven effective in improving glycated hemoglobin (HbA1c) in type 2 diabetes mellitus (T2DM) patients. However, it is unclear if needle-free and needle injections of insulin during intensive insulin therapy in hospitalized patients provide similar efficacy and safety benefits. Methods: A self-controlled cross-over study was conducted on 62 patients with T2DM who received intensive long-acting and short-acting insulin injections with or without needles. The 7-point blood glucose test was performed on the 6th day after insulin administration and the injection method switched on the 7th day of hospitalization. The difference was compared in 7-point blood glucose levels. Results: The blood glucose levels at fasting (mean difference=-1.09 ± 2.38mmol/L, 95% CI, -1.69 to -0.48, p=0.0007) and post-breakfast (-1.14 ± 3.02mmol/L, 95%CI, -1.91 to -0.37, p=0.004) were better when patients were receiving needle-free injections compared to when receiving a needle injection. Indeed, daily blood glucose fluctuation, which presented as the area under the curve of glycemia, was decreased in needle-free injection periods (-0.3.48 ± 9.64, 95%CI, -5.95 to -1.01, p=0.0065). There was no significant difference in the dose of long-acting insulin between the two injection methods (-0.32 ± 2.69, 95%CI, -0.99 to 0.37, p>0.05). The dose of fast-acting insulin during the needle-free period was lower than that of when patients received needle injections (-1.66 ± 6.45, 95%CI, -3.29 to -0.025, p<0.05). There was no significant difference in satisfaction between the two regimens (-0.59 ± 1.55,95%CI, -0.938 to 0.509, p=0.557), but there was a significant difference in pain experience, favoring needle-free injections (p < 0.001). Conclusion: Glycemia was better controlled by needle-free insulin injections in hospitalized T2DM patients subjected to intensive glycemic control. These patients also experienced less pain than when insulin was injected with a needle.

Acute change of lung function to short-term exposure to ambient air pollutants with and without physical activity: A real-world crossover study.

Physical activity (PA) would increase the inhalation rate and thereby inhaled dose of air pollutants. However, it's still uncertain whether the effects of air pollutants on lung function are attenuated by PA, especially in the high-polluted areas. We aimed to disentangle the interaction between air pollution and PA on lung function among healthy adults. In this study, a real-world crossover study was conducted among 74 healthy adults. Each participant underwent both rest and 15-min intermittent moderate PA exposure scenarios (consisting of 15min stationary bike riding alternating with 15min of rest), which lasted for 2 h. On the same day, the participants among active and inactive group were exposed to the same air pollution. We have monitored the fine particulate matter (PM2.5), particulate matter less than 10 µm (PM10), particulate matter less than 1 µm (PM1), black carbon (BC), nitrogen dioxide (NO2), and ozone (O3) continuously during 2-h exposure. Lung function were measured at five times points for each visit (before, immediately, 3 h, 5 h, and 24 h after the 2-h exposure scenario). Mixed-effects models were applied to explore the effects of air pollution, PA, and their interaction on lung function. The participants had a mean (standard deviation (SD)) age of 19.9 (0.9) years. The average concentration [mean ± SD] of PM2.5, PM10, PM1, BC, NO2, and O3 were 59.4 ± 45.1 µg/m3, 122.8 ± 109.0 µg/m3, 38.8 ± 29.2 µg/m3, 1.94 ± 1.17 µg/m3, 59.5 ± 26.6 µg/m3, and 74.0 ± 30.3 µg/m3, respectively. Overall, greater increasement in lung function were observed among active group compared with inactive group at all timepoints. In fully adjusted models, we observed the benefits of PA and detrimental effects of air pollutants on lung function. Our results suggested that PA, compared to rest, alleviated the detrimental effects of air pollutants on lung function. We also stressed the importance of timing of measurements for capturing association. In conclusion, our observations suggested that PA might alleviate the associations between various pollutant exposures and lung function, which would drive further research towards potential pathway.

Enrichment of n-3 containing ether phospholipids in plasma after 30 days of krill oil compared with fish oil supplementation.

There are conflicting findings over the bioavailability of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) from krill oil (KO) compared with fish oil (FO) in short- and long-term studies. The aim of this study was to compare the effects of KO versus FO on the enrichment of molecular species of plasma phospholipids in young women following a 30-day consumption of the n-3 oils. Eleven healthy women aged 18-45 years consumed seven capsules of KO per day (containing a total of 1.27 g n-3 PUFA) or five capsules of FO per day (total of 1.44 g n-3 PUFA) for 30 days in a randomized crossover study, separated by at least a 30-day washout period. Fasting blood samples were collected at day zero (baseline), day 15 and day 30 and analyzed by HPLC-MS/MS for molecular species of phospholipids. Supplementation increased n-3 PUFA in main phospholipids classes in both groups. After 30 days of supplementation, 35 out of 70 molecular species containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPAn-3) had a significantly greater concentration in KO group compared with the FO treated group. The majority (89%) of the differentiated molecular species were choline and ethanolamine ether-phospholipids. These data reveal that analysis of plasma phospholipids following 30 days of consumption of KO (a marine oil rich in phospholipids, including ether phospholipids) resulted in an enrichment of n-3 PUFA in molecular species of ether-phospholipids compared with FO (a triacylglycerol-rich marine oil).

Different elemental infant formulas show equivalent phosphorus and calcium bioavailability in healthy volunteers.

Retrospective chart reviews have reported hypophosphatemia associated with elemental formula use in infants and children with systemic disease involving multiple diagnoses. The present study aims to evaluate the bioavailability of phosphorus from 2 commercial elemental formulas and to test our hypothesis of bioequivalence of the 2 products in healthy volunteers receiving gastric acid-suppressive medication. A single-center, double-blind, randomized, cross-over study was conducted in healthy volunteers with esomeprazole-induced hypochlorhydria. After a standardized low phosphorus meal followed by overnight fasting, subjects consumed 1 gram of phosphorus in a single oral dose of 1217 kcal of Product A (Neocate) or Product B (Elecare). The alternate product was given following a 1-week washout period. Blood and urine were collected at baseline and different time-points for up to 6 hours after product consumption. Area-under-the-curve (AUC) and peak values (Cpeak) for serum phosphate and calcium and urinary creatinine-corrected phosphate and calcium were assessed for bioequivalence of Products A and B. Results show that the geometric mean ratio (GMR) and 90% CI for serum phosphate were 1.041 (0.998-1.086) and 1.020 (0.963-1.080) for AUC0-360 and Cpeak, respectively, meeting the predetermined criteria for bioequivalence. Urinary creatinine-corrected phosphate followed a similar pattern after intake of Product A and B, but did not reach bioequivalence criteria (GMR: AUC70-370 = 1.105 (0.918-1.330); Cpeak = 1.182 (1.040-1.343)). Serum calcium concentrations (GMR: AUC0-360 = 1.002 (0.996-1.009); Cpeak = 0.991 (0.983-0.999)) and urinary creatinine-corrected calcium excretion (GMR: AUC70-370 = 1.117 (1.023-1.219); Cpeak = 1.157 (1.073-1.247)) demonstrated bioequivalence of the products. In conclusion, both elemental infant formulas showed equivalent serum phosphorus and calcium bioavailability in healthy volunteers even if combined with treatment with acid-suppressive medication.

Methodological Challenges Encountered in a Study of the Impact of Animal-assisted Intervention in Pediatric Heart Transplant Patients.

PURPOSE: The purpose of this pilot study was to examine the impact of animal-assisted intervention (AAI) on ambulation, physiologic stability, patient satisfaction, and perceived benefit in hospitalized pediatric heart transplant patients. DESIGN AND METHODS: This pilot study used a two-period, two-sequence cross-over design. Using a convenience sample of heart transplant patients between the ages six and nineteen, each subject participated in one AAI and one non-AAI study session over one week. All study sessions started with an aspect of walking. RESULTS: Three males and two females participated. Average age was 15 years. Subjects walked on average 1906 ft during the AAI session as compared to 1933 ft in the non-AAI session. Subjects spent a longer time (17 min) walking in the AAI session as compared to the non-AAI session (15 min). Blood pressure and respiratory rates remained stable. All subjects reported they liked working with the dog. Eighty percent of subjects actively engaged in physical contact and communication with the dog. No safety-related adverse events were reported. CONCLUSIONS: AAI may assist adolescent heart transplant patients to be more motivated to participate in therapeutic ambulation when walking with a dog. Further studies are needed to identify successful recruitment strategies in this highly vulnerable patient population. PRACTICE IMPLICATIONS: Many clinical challenges exist in implementing AAI research in the pediatric heart transplant population. A conceptual model is introduced to better understand the methodological challenges of conducting AAI research in the hospital setting. Key components include research, organizational, AAI, subject and time factors.

Using Bluetooth beacon technology to reduce distracted pedestrian behaviour: a cross-over trial study protocol.

OBJECTIVE: Over 6400 American pedestrians die annually, a figure that is currently increasing. One hypothesised reason for the increasing trend is the role of mobile technology in distracting both pedestrians and drivers. Scientists and policy-makers have attended somewhat to distracted driving, but attention to distracted pedestrian behaviour has lagged. We will evaluate Bluetooth beacon technology as a means to alert and warn pedestrians when they approach intersections, reminding them to attend to the traffic environment and cross streets safely. METHODS: Bluetooth beacons are small devices that broadcast information unidirectionally within a closed proximal network. We will place beacons at an intersection frequently trafficked by urban college students. From there, the beacons will transmit to an app installed on users' smartphones, signalling users to attend to their environment and cross the street safely. A cross-over trial will evaluate the app with 411 adults who frequently cross the target intersection on an urban university campus. We will monitor those participants' behaviour over three distinct time periods: (1) 3 weeks without the app being activated, (2) 3 weeks with the app activated and (3) 4 weeks without the app activated to assess retention of behaviour. Throughout the 10-week period, we will gather information to evaluate whether the intervention changes distracted pedestrian behaviour using a logistic regression to estimate the likelihood of key behavioural outcome measures and adjusting for any residual confounding. We also will test for changes in perceived risk. The trial will follow CONSORT (Consolidated Standards of Reporting Trials) statement guidelines, as modified for cross-over design studies. CONCLUSION: If this program proves successful, it offers exciting implications for future testing and ultimately for broad distribution to reduce distracted pedestrian behavior. We discuss issues of feasibility, acceptability and scalability.

Efficacy and safety of videolaryngoscopy-guided verbal feedback to teach neonatal and infant intubation. A prospective randomised cross over study.

BACKGROUND AND AIMS: Neonatal endotracheal intubation is challenging due to the miniature anatomy, which is distinct from adults and reserves only less oxygen and time before desaturation begins. As a result, teaching neonatal intubation becomes fraught with difficulties. This study aimed to determine the efficacy and safety of videolaryngoscopy-guided verbal feedback compared to conventional laryngoscopy verbal feedback in neonatal and infant intubation. METHODS: In this prospective randomised cross over study, 24 trainees were randomly allocated to two groups, video-assisted verbal feedback followed by conventional verbal feedback (V/C) and conventional verbal feedback followed by video-assisted verbal feedback (C/V). one hundred forty-four ASA grade I-II patients aged 1 day to 6 months requiring general anaesthesia with endotracheal intubation were included. Each trainee performed three intubations with one technique and switched to other technique to perform three more intubations. Primary outcome was first attempt success rate and secondary outcomes were time to best view, time to intubation, ease of intubation, manoeuvres used and complications. RESULTS: Overall first attempt intubation success rate was higher with video-assisted verbal feedbacks compared to conventional verbal feedback (83.3% vs. 44.4%, P value = <0.001). The time to best view (19.8 s vs. 26.8 s, P value = <0.001) and intubation (30 s vs. 41.7 s) was achieved faster with video-assisted part of the study. CONCLUSION: Our study results show that video-assisted verbal feedback to trainees resulted in high intubation success rate and reduced complications like oesophageal intubation and desaturation in neonatal and infant intubations.

Systematic Assessment of Blood-Borne MicroRNAs Highlights Molecular Profiles of Endurance Sport and Carbohydrate Uptake.

Multiple studies endorsed the positive effect of regular exercise on mental and physical health. However, the molecular mechanisms underlying training-induced fitness in combination with personal life-style remain largely unexplored. Circulating biomarkers such as microRNAs (miRNAs) offer themselves for studying systemic and cellular changes since they can be collected from the bloodstream in a low-invasive manner. In Homo sapiens miRNAs are known to regulate a substantial number of protein-coding genes in a post-transcriptional manner and hence are of great interest to understand differential gene expression profiles, offering a cost-effective mechanism to study molecular training adaption, and connecting the dots from genomics to observed phenotypes. Here, we investigated molecular expression patterns of 2549 miRNAs in whole-blood samples from 23 healthy and untrained adult participants of a cross-over study, consisting of eight weeks of endurance training, with several sessions per week, followed by 8 weeks of washout and another 8 weeks of running, using microarrays. Participants were randomly assigned to one of the two study groups, one of which administered carbohydrates before each session in the first training period, and switching the treatment group for the second training period. During running sessions clinical parameters as heartbeat frequency were recorded. This information was extended with four measurements of maximum oxygen uptake (VO 2 max) for each participant. We observed that multiple circulating miRNAs show expression changes after endurance training, leveraging the capability to separate the blood samples by training status. To this end, we demonstrate that most of the variance in miRNA expression can be explained by both common and known biological and technical factors. Our findings highlight six distinct clusters of miRNAs, each exhibiting an oscillating expression profile across the four study timepoints, that can effectively be utilized to predict phenotypic VO 2 max levels. In addition, we identified miR-532-5p as a candidate marker to determine personal alterations in physical training performance on a case-by-case analysis taking the influence of a carbohydrate-rich nutrition into account. In literature, miR-532-5p is known as a common down-regulated miRNA in diabetes and obesity, possibly providing a molecular link between cellular homeostasis, personal fitness levels, and health in aging. We conclude that circulating miRNA expression can be altered due to regular endurance training, independent of the carbohydrate (CHO) availability in the training timeframe. Further validation studies are required to confirm the role of exercise-affected miRNAs and the extraordinary function of miR-532-5p in modulating the metabolic response to a high availability of glucose.

Comparison of Plaque Removal and Wear between Charcoal Infused Bristle and Nylon Bristle Toothbrushes: A Randomized Clinical Crossover Study.

AIM: To compare plaque removal and wear between charcoal infused bristle toothbrushes (T1) and nylon bristle toothbrushes (T2) in a randomized clinical crossover study. MATERIALS AND METHODS: A cross-over study was conducted in 2 phases of 6 weeks duration each with an intervening 2-week washout. Twenty-five participants meeting inclusion criteria were randomly allocated into groups A (13) and B (12). In phase 1: group A was assigned T1 and group B was assigned T2. Toothbrushing was advised twice daily for 2 minutes by modified bass technique after meals. At baseline, 3 weeks and 6 weeks the wear index (WI), plaque index (PI) and gingival index (GI) were recorded. Following washout in phase 2 group A was assigned T2 and group B was assigned T1 and the same study protocol was followed. RESULTS: Intra-group comparison between baseline, 3 and 6 weeks by the paired t-test resulted in significant reduction in PI, GI and increase in WI (p <0.05) for T1 and T2. Inter-group comparison using the unpaired t-test resulted in WI for T1 being significantly higher (p <0.05) at 3 weeks and lower at 6 weeks (p <0.05) compared to T2. PI for T1 was significantly higher at 3 weeks (p <0.05) and lower at 6 weeks (p <0.05) compared to T2. No significant difference in GI scores between T1 and T2 at 3 and 6 weeks was observed (p >0.05). CONCLUSION: Charcoal infused bristles demonstrated less wear and more plaque removal compared to nylon bristles. CLINICAL SIGNIFICANCE: Charcoal infused bristles demonstrate less wear compared to nylon bristles.

Effect of home-based transcranial direct current stimulation (tDCS) on cognitive function in patients with mild cognitive impairment: a study protocol for a randomized, double-blind, cross-over study.

BACKGROUND: The possible effect of transcranial direct current stimulation (tDCS) in improving cognitive function is clear from studies involving pre-dementia stage mild cognitive impairment (MCI). However, the application of tDCS in actual clinical practice entails repeated hospital visits almost every day for treatment. The objective of this study is to confirm the possibility of self-application of tDCS at home by elderly patients with declined cognitive function and the significant clinical effect of tDCS administered at home. METHODS/DESIGN: This study will be conducted in 20 elderly people aged 60 to 80 years with complaints of subjective memory impairment while maintaining general functions with limited activities of daily living. This study involves a cross-over design that will include 2-week active or sham stimulation of both dorsolateral prefrontal cortexes (left, anode; right, cathode) randomly with a 2-week wash-out phase. Changes in cognitive function will be evaluated using visual recognition tasks and neuropsychological tests. In this study, tDCS will be carried out by each patient at his/her home and its safety and suitability will be evaluated. DISCUSSION: In this study, patients will apply a portable tDCS, developed for home use, for more than 2 weeks. Such studies can contribute to the use of tDCS as a realistic therapy. In addition, the utility of home-based tDCS will be confirmed by application of tDCS at home by the elderly with declined cognitive function. Furthermore, confirmation of tDCS as a significant therapeutic method can facilitate treatment of Alzheimer's dementia at an early stage, including MCI. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), KCT0002721 . Registered on 9 March 2018.

Comparison of antiplaque effectiveness of herbal toothpaste: A randomized triple-blinded cross-over clinical trial.

BACKGROUND: Cleansing the teeth with a toothbrush and paste is an indubitable mechanical plaque control method practiced by almost everyone. Eliminating dental plaque is an essential, fundamental and mandatory step to prevent the occurrence of periodontal diseases that are rife globally. The aim of the present study is to compare the antiplaque effectiveness of a prepared herbal and commercially available dentifrice. MATERIALS AND METHODS: Thirty healthy individuals within the age group of 18-25 years were recruited to participate in the study. After achieving induced gingivitis and measuring plaque levels using Turesky modification of the Quigley Hein Plaque index in all the subjects, they were randomly divided into test arms A and B. Commercial dentifrice was distributed to one group, whereas the other group received prepared herbal dentifrice. Supervised brushing was carried out for 5 min, and plaque amounts after brushing were noted. After a washout period of 1 week, the same steps were repeated as per the cross-over study protocol. Unpaired t-test and paired t-tests were employed with P < 0.05. RESULTS: Both the toothpastes show the difference in plaque scores immediately after brushing when compared to baseline and was statistically significant (P = 0.001). The mean plaque scores of commercial dentifrice (1.93 ± 1.52) were less than that of the prepared herbal dentifrice (2.35 ± 1.39) after brushing. CONCLUSION: The prepared herbal dentifrice had good antiplaque action. However, the plaque inhibitory action of self-prepared herbal toothpaste was marginally less when compared to commercial dentifrice.

Comparison of electropharmacological effects between terfenadine and its active derivative fexofenadine using a cross-over study in halothane-anesthetized dogs to analyze variability of pharmacodynamic and pharmacokinetic profiles of terfenadine and torsadogenic risk of fexofenadine.

In order to better understand the variability of pharmacodynamic and pharmacokinetic profiles of terfenadine between the previous studies as well as to qualitatively and quantitatively examine the proarrhythmic potential of its major active metabolite fexofenadine in comparison with that of terfenadine, we directly compared their electropharmacological effects with halothane-anesthetized dogs (n = 3). For this purpose, we adopted a cross-over design, which can directly compare the effects of terfenadine and fexofenadine under the identical metabolic condition. Terfenadine in doses of 0.03 and 0.3 mg/kg increased the mean blood pressure, but that of 3 mg/kg decreased it. Terfenadine also increased the heart rate and ventricular contractility in a dose-related manner; but delayed the atrioventricular nodal and intraventricular conductions as well as repolarization suggesting its proarrhythmic potential. Meanwhile, fexofenadine in the same dose increased the mean blood pressure in a dose-related manner without affecting any of the electrophysiological variables in the same animals that proarrhythmic risk of terfenadine was confirmed, indicating its lack of proarrhythmic risk. Peak plasma concentrations for fexofenadine were 3.7, 8.1 and 11.2 times greater than for terfenadine at each matching dose, indicating terfenadine may be metabolized much faster than fexofenadine. Taken together, after the low and middle doses of terfenadine, vasopressor effect of a metabolite fexofenadine could be greater than the depressor effect of parent compound terfenadine, but its reverse would be correct after the high dose. Thus, the cross-over analysis can be an effective way to better understand drug-induced cardiovascular responses.

Efficacy of Alternating Conventional Stimulation and High Frequency Stimulation in Improving Spinal Cord Stimulation Outcomes: A Pilot Study.

INTRODUCTION: Spinal cord stimulation (SCS) is an established, effective method of treating chronic pain. High frequency stimulation (HFS) is an alternative SCS waveform that has been shown to alleviate pain but also necessitates more frequent recharging. The purpose of this pilot study is to evaluate efficacy of alternating conventional stimulation and HFS (termed "shuffle" stimulation) in improving SCS outcomes. METHODS: Shuffle stimulation was designed to deliver conventional stimulation in upright positions with relative HFS in lying positions, automated through accelerometer technology. In this 13-week cross-over study, patients were randomized to receiving conventional and shuffle stimulation in four-week blocks. Pain outcomes and sensory testing were compared from preoperative baseline and at the conclusion of each study period. RESULTS: Twelve patients completed this study. Two patients showed no change from baseline visual analogue scale (VAS) with either type of stimulation and were excluded from statistical analysis of pain outcomes. Mean numerical rating scale (NRS) scores assessing current pain were significantly lower in shuffle stimulation (4.0 ± 1.6) compared to conventional stimulation (5.8 ± 2.3) (p = 0.024). In the total cohort, 7 of 11 patients preferred shuffle over conventional stimulation. CONCLUSIONS: This study generated preliminary evidence showing improved NRS current pain scores in shuffle stimulation compared to conventional stimulation. More patients preferred shuffle stimulation compared to conventional stimulation. Optimizing stimulation when patients are recumbent may increase patient satisfaction and pain control. The potential advantages of shuffle stimulation may warrant further investigation.

177Lu-PSMA-617 radioligand therapy for a patient with lymph node metastatic prostate cancer.

Prostate specific membrane antigen (PSMA) is expressed in unfavorable prostate cancer. PSMA is basis for new diagnostics and theranostics. PET/CT using PSMA is more sensitive than choline PET/CT. 177Lu-PSMA radioligand therapy is mainly used for patients with end-stage prostate cancer. This report describes a patient with a third recurrence in lymph nodes. The recurrence was treated with 177Lu-PSMA radioligand therapy instead of chemotherapy with docetaxel. The effect was in part evaluated relative to that of two established salvage treatments. Prior salvage radiotherapy and abiraterone of the first and second recurrence in lymph nodes had given only a partial reduction of PSA. Nevertheless within five months of follow-up, 177Lu-PSMA radioligand therapy of the third recurrence in lymph nodes reduced PSA for a period to unmeasurable levels. 177Lu-PSMA radioligand therapy gave only mild adverse effects. In conclusion, for a patient with lymph node metastatic prostate cancer, 177Lu-PSMA-617 radioligand therapy had an attractive therapeutic profile. A follow-up study of similar patients is being planned.

Assessing the contact-activation of coagulation during hemodialysis with three different polysulfone filters: A prospective randomized cross-over trial.

INTRODUCTION: During hemodialysis (HD) the interaction of the blood with the dialyzer triggers both an inflammatory reaction and an activation of the coagulation cascade. An accepted parameter to quantify the extent of coagulation activation during HD is not available. This study aims to evaluate its amplitude, comparing dialyzers made of different polysulfone polymers, by measuring D-dimers in the filter-rinsing fluids (Frf) and to test whether Frf D-dimers are suitable candidate markers to assess contact coagulation activation during HD. METHODS: In a prospective, cross-over study 41 hemodialysis patients were randomly allocated to nine HD sessions with three types of polysulfone membranes: Filter A: Poliflux®RevaclearMAX; Filter B: Helixone®Fx80, Filter C: Polyflux®H210. FINDINGS: A total of 117 HD sessions were studied. The mean (SD) filter (Frf) D-dimers were 0.19 µg/L (0.56) for Filter A; 0.66 µg/L (2.81) for Filter B; 0.33 µg/L (1.13) for Filter C. Significant differences were found: A vs. B (P < 0.01), A vs. C (P = 0.01); B vs. C not significant. A large between-patient variability of D-dimer filter levels was found. D-Dimers in blood showed a similar trend but differences were not significant. DISCUSSION: The contact activation of coagulation during HD may also vary among filters made up with similar polysulfones. D-dimer in the filter rinsing fluid but not in the blood can be considered a candidate marker for the evaluation of thrombogenicity during HD. Further studies are needed to elucidate the mechanism(s) and to confirm the usefulness of filter rinsing fluid D-Dimers as a clotting activation marker during HD.

Vitamin D3 supplementation in healthy adults: a comparison between capsule and oral spray solution as a method of delivery in a wintertime, randomised, open-label, cross-over study.

Vitamin D is typically supplied in capsule form, both in trials and in clinical practice. However, little is known regarding the efficacy of vitamin D administered via oral sprays - a method that primarily bypasses the gastrointestinal absorption route. This study aimed to compare the efficacy of vitamin D3 liquid capsules and oral spray solution in increasing wintertime total 25-hydroxyvitamin D (25(OH)D) concentrations. In this randomised, open-label, cross-over trial, healthy adults (n 22) received 3000 IU (75 µg) vitamin D3 daily for 4 weeks in either capsule or oral spray form. Following a 10-week washout phase, participants received the opposite treatment for a final 4 weeks. Anthropometrics and fasted blood samples were obtained before and after supplementation, with samples analysed for total 25(OH)D, creatinine, intact parathyroid hormone and adjusted Ca concentrations. At baseline, vitamin D sufficiency (total 25(OH)D>50 nmol/l), insufficiency (31-49 nmol/l) and clinical deficiency (<30 nmol/l) were evident in 59, 23 and 18 % of the participants, respectively. Overall, baseline total mean 25(OH)D concentration averaged 59·76 (sd 29·88) nmol/l, representing clinical sufficiency. ANCOVA revealed no significant difference in the mean and standard deviation change from baseline in total 25(OH)D concentrations between oral spray and capsule supplementation methods (26·15 (sd 17·85) v. 30·38 (sd 17·91) nmol/l, respectively; F=1·044, adjusted r 2 0·493, P=0·313). Oral spray vitamin D3 is an equally effective alternative to capsule supplementation in healthy adults.

Effects of pressure applied during standardized spinal mobilizations on peripheral skin blood flow: A randomised cross-over study.

BACKGROUND: Peripheral skin blood flow (SBF) changes during and after spinal mobilization (SM), evaluated with laser Doppler flowmetry, may document physiological responses associated with SM. OBJECTIVES: To document variations in SBF during and after application of an SM and evaluate influence of pressure on SBF by applying the same standardized SM with 3 different nonnoxious pressures. DESIGN: Cross-over design with 4 interventions on 4 different days: control (no touch) and 3 SMs applied rhythmically at 5%, 40%, or 80% of pain pressure threshold (sham SM, low-pressure SM, or high-pressure SM, respectively). METHOD: Thirty-two individuals participated. The inspiratory gasp (IG) test was our positive control of vasoconstriction through excitation of the skin sympathetic nervous activity (SSNA). Each session comprised 5 phases: (1) baseline at the end of a 20-min acclimatization, (2) IG test, (3) post-IG phase, (4) SM phase or no manual contact for control, and (5) post-SM phase. A Biopac MP36 system collected SBF data, and a Novel Pliance-X system recorded pressure data. RESULTS/FINDINGS: Equal and significant bilateral vasodilation occurred during application of unilateral sham SM, low-pressure SM, and high-pressure SM. Post-SM significant vasodilation persisted after high-pressure SM. CONCLUSIONS: The current study is the first to describe bilateral peripheral SBF changes occurring during and 5 min after application of standardized SMs. Our post-SM vasodilation suggests involvement of mechanisms other than the putative SSNA-excitatory mechanism proposed with skin conductance measurements. Persistence of post-SM vasodilation following only high-pressure SM suggests possible pressure-dependent mechanisms. However, further research is warranted to clarify our findings.