Effects of combined exercises on shoulder mobility and strength of the upper extremities in breast cancer rehabilitation: a 3-week randomized controlled trial.

PURPOSE: The aim of this study was to analyze the effects of mobility training with FIVE® devices in combination with device-supported strength exercises for shoulder mobility and strength of the upper extremities in women with breast cancer. METHODS: We conducted a pretest-posttest intervention study with female breast cancer patients (n = 41) who were randomly assigned to two groups by lot during their stationary follow-up treatment at a rehabilitation clinic in the south of Germany between February and March 2020. As part of exercise therapy, the intervention group (n = 24) performed a mobility training with FIVE® devices combined with device-supported strength training, whereas the control group (n = 17) completed device-supported strength training. Before and after the 3-week intervention (3 training sessions/week), shoulder mobility and isokinetic maximal strength were tested. RESULTS: Both groups achieved significant improvements in shoulder mobility in the frontal and sagittal plane (between 3.8 and 15.35%; p < 0.05) and in strength performance (31.36% [IG] vs. 51.24% [CG]; p < 0.001). However, no robust evidence could be determined about potential interaction effects. CONCLUSION: A combined device-supported strength and mobility training (FIVE®) showed no advantages. Therefore, a variety of exercise methods is possible in exercise therapy of breast cancer patients. CLINICAL TRIAL REGISTRATION NUMBER: Since the University of Education Weingarten does not assign clinical trial registration numbers or ethical approval numbers, none could be assigned for this study.

Accelerated quantification of amphetamine enantiomers in human urine using chiral liquid chromatography and on-line column-switching coupled with tandem mass spectrometry.

Amphetamine (AM) is a powerful psychostimulant existing in two enantiomeric forms. Stereoselective analysis of AM in biosamples can assist clinicians and forensic experts in differentiating between abuse of illicitly synthesized racemic AM and ingestion of pharmaceutical AM formulations containing either S-AM or different proportions of the S- and R-enantiomers. Therefore, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying AM enantiomers in urine was newly developed. The method comprised dilution with water, followed by injection of the diluted sample onto an achiral C18 trapping column for purification and subsequent backflush elution to a chiral Lux 3 µm AMP LC column by means of a switching valve. An isocratic mobile phase of 25 % acetonitrile in 0.1 M aqueous ammonia was used for enantiomeric separation. Injection, cleanup, and backflush of the next sample were performed before the previous sample had eluted from the analytical column, thus enabling simultaneous enantioseparation of up to three samples within the analytical column. This novel chromatographic concept allowed for increased sample throughput by accelerating both the sample preparation and the LC analysis. Analyte detection was accomplished by electrospray ionization in positive ion mode and selected reaction monitoring using a triple-stage quadrupole mass spectrometer. The method was successfully validated through assessment of its linearity, lower limit of quantification, accuracy and precision, selectivity, matrix effect, carry-over, dilution integrity, and re-injection reproducibility. Linearity ranged from 0.05 to 25 mg/L for both enantiomers. Proof of the method included analysis of urine samples obtained from drug abusers and patients receiving an S-AM prodrug. Graphical Abstract Enantioselective determination of amphetamine in human urine using liquid chromatography with achiral-chiral column-switching and tandem mass spectrometry.

MEMS and FOG Technologies for Tactical and Navigation Grade Inertial Sensors-Recent Improvements and Comparison.

In the following paper, we present an industry perspective of inertial sensors for navigation purposes driven by applications and customer needs. Microelectromechanical system (MEMS) inertial sensors have revolutionized consumer, automotive, and industrial applications and they have started to fulfill the high end tactical grade performance requirements of hybrid navigation systems on a series production scale. The Fiber Optic Gyroscope (FOG) technology, on the other hand, is further pushed into the near navigation grade performance region and beyond. Each technology has its special pros and cons making it more or less suitable for specific applications. In our overview paper, we present latest improvements at NG LITEF in tactical and navigation grade MEMS accelerometers, MEMS gyroscopes, and Fiber Optic Gyroscopes, based on our long-term experience in the field. We demonstrate how accelerometer performance has improved by switching from wet etching to deep reactive ion etching (DRIE) technology. For MEMS gyroscopes, we show that better than 1°/h series production devices are within reach, and for FOGs we present how limitations in noise performance were overcome by signal processing. The paper also intends a comparison of the different technologies, emphasizing suitability for different navigation applications, thus providing guidance to system engineers.

Application of phosphatidylethanol (PEth) in whole blood in comparison to ethyl glucuronide in hair (hEtG) in driving aptitude assessment (DAA).

For driving aptitude assessment (DAA), the analysis of several alcohol biomarkers is essential for the detection of alcohol intake besides psycho-medical exploration. In Switzerland, EtG in hair (hEtG) is often the only direct marker for abstinence monitoring in DAA. Therefore, the suitability of phosphatidylethanol (PEth) was investigated as additional biomarker. PEth 16:0/18:1 and 16:0/18:2 were determined by online-SPE-LC-MS/MS in 136 blood samples of persons undergoing DAA and compared to hEtG, determined in hair segments taken at the same time. With a PEth 16:0/18:1 threshold of 210 ng/mL for excessive alcohol consumption, all (n = 30) but one tested person also had hEtG values ≥30 pg/mg. In 54 cases, results are not in contradiction to an abstinence as neither PEth (<20 ng/mL) nor hEtG (<7 pg/mg) was detected. In eight cases, both markers showed moderate consumption. Altogether, PEth and hEtG were in accordance in 68 % of the samples, although covering different time periods of alcohol consumption. With receiver operating characteristic analysis, PEth was evaluated to differentiate abstinence, moderate, and excessive alcohol consumption in accordance with hEtG limits. A PEth 16:0/18:1 threshold of 150 ng/mL resulted in the best sensitivity (70.6 %) and specificity (98.8 %) for excessive consumption. Values between 20 and 150 ng/mL passed for moderate consumption, values <20 ng/mL passed for abstinence. As PEth mostly has a shorter detection window (2-4 weeks) than hEtG (up to 6 months depending on hair length), changes in drinking behavior can be detected earlier by PEth than by hEtG analysis alone. Therefore, PEth helps to improve the diagnostic information and is a valuable additional alcohol marker for DAA.

Phosphatidylethanol (PEth) in blood samples from "driving under the influence" cases as indicator for prolonged excessive alcohol consumption.

Phosphatidylethanol (PEth) is considered as specific biomarker of alcohol consumption. Due to accumulation after repeated drinking, PEth is suitable to monitor long-term drinking behavior. To examine the applicability of PEth in "driving under the influence of alcohol" cases, 142 blood samples with blood alcohol concentrations (BAC) ranging from 0.0-3.12‰ were analyzed for the presence of PEth homologues 16:0/18:1 (889 ± 878 ng/mL; range

Determination of fatty acid ethyl esters in dried blood spots by LC-MS/MS as markers for ethanol intake: application in a drinking study.

The forensic utility of fatty acid ethyl esters (FAEEs) in dried blood spots (DBS) as short-term confirmatory markers for ethanol intake was examined. An LC-MS/MS method for the determination of FAEEs in DBS was developed and validated to investigate FAEE formation and elimination in a drinking study, whereby eight subjects ingested 0.66-0.84 g/kg alcohol to reach blood alcohol concentrations (BAC) of 0.8 g/kg. Blood was taken every 1.5-2 h, BAC was determined, and dried blood spots were prepared, with 50 µL of blood, for the determination of FAEEs. Lower limits of quantitation (LLOQ) were between 15 and 37 ng/mL for the four major FAEEs. Validation data are presented in detail. In the drinking study, ethyl palmitate and ethyl oleate proved to be the two most suitable markers for FAEE determination. Maximum FAEE concentrations were reached in samples taken 2 or 4 h after the start of drinking. The following mean peak concentrations (c̅(max)) were reached: ethyl myristate 14 ± 4 ng/mL, ethyl palmitate 144 ± 35 ng/mL, ethyl oleate 125 ± 55 ng/mL, ethyl stearate 71 ± 21 ng/mL, total FAEEs 344 ± 91 ng/mL. Detectability of FAEEs was found to be on the same time scale as BAC. In liquid blood samples containing ethanol, FAEE concentrations increase post-sampling. This study shows that the use of DBS fixation prevents additional FAEE formation in blood samples containing ethanol. Positive FAEE results obtained by DBS analysis can be used as evidence for the presence of ethanol in the original blood sample.

Development of a rapid column-switching LC-MS/MS method for the quantification of THCCOOH and THCCOOH-glucuronide in whole blood for assessing cannabis consumption frequency.

The concentration of 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol (THCCOOH) in whole blood is used as a parameter for assessing the consumption behavior of cannabis consumers. The blood level of THCCOOH-glucuronide might provide additional information about the frequency of cannabis use. To verify this assumption, a column-switching liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the rapid and direct quantification of free and glucuronidated THCCOOH in human whole blood was newly developed. The method comprised protein precipitation, followed by injection of the processed sample onto a trapping column and subsequent gradient elution to an analytical column for separation and detection. The total LC run time was 4.5 min. Detection of the analytes was accomplished by electrospray ionization in positive ion mode and selected reaction monitoring using a triple-stage quadrupole mass spectrometer. The method was fully validated by evaluating the following parameters: linearity, lower limit of quantification, accuracy and imprecision, selectivity, extraction efficiency, matrix effect, carry-over, dilution integrity, analyte stability, and re-injection reproducibility. All acceptance criteria were analyzed and the predefined criteria met. Linearity ranged from 5.0 to 500 µg/L for both analytes. The method was successfully applied to whole blood samples from a large collective of cannabis consumers, demonstrating its applicability in the forensic field.

N-Acetyltaurine as a novel urinary ethanol marker in a drinking study.

The forensic utility of N-acetyltaurine (NAcT) in urine as a marker for ethanol intake was examined. A HILIC-based liquid chromatography method for the mass spectrometric determination of NAcT, taurine, and creatinine in urine was developed and validated to investigate NAcT formation and elimination in a drinking study. Thereby, eight subjects ingested 0.66 to 0.84 g/kg alcohol to reach a blood alcohol concentration (BAC) of 0.8 g/kg. Blood and urine were taken every 1.5-2 h, during the first 8 h. NAcT and taurine levels were measured and corrected for the urine's dilution by normalization to a creatinine concentration of 1 mg/mL. For the determination of NAcT and taurine, uncorrected lower limits of quantitation (LLOQs) were at 0.05 µg/mL of urine. In the drinking study, NAcT proved to be an endogenous compound, which is present at a range of 1.0 to 2.3 µg/mL in urine of alcohol-abstinent subjects. Maximum NAcT concentrations were reached in samples taken 3 to 6 h after the start of drinking, whereby an upregulation in N-acetyltaurine could be found for all the subjects. The mean peak concentrations (c̅ max) of 14 ± 2.6 µg/mL (range 9-17.5 µg/mL) were reached. Within 24 h, the NAcT levels declined to endogenous concentrations. The detectability of NAcT was found to be slightly shifted compared to BAC: When BAC was not detectable anymore, NAcT levels were still elevated. After 24 h, when ethyl glucuronide (EtG) and ethyl sulfate (EtS) were still detectable, NAcT concentrations showed endogenous levels again. Positive NAcT results can be used as an indicator for recent alcohol consumption. A direct relationship between NAcT and taurine concentrations could not be found. Graphical abstract N-acetyltaurine concentrations for eight subjects during the first 24 h after an alcohol consumption of 0.8 g/kg.

Surgical planning, manufacturing and implantation of an individualized cervical fusion titanium cage using patient-specific data.

BACKGROUND: Most cervical fusion cages imperfectly mimic the anatomy of the intervertebral disc space. The production of individualized cages might be the next step to further improve spinal implants due to their enhanced load-bearing surface. OBJECTIVE: To evaluate the planning, manufacturing, and implantation of an individualized cervical cage in co-operation with EIT and 3D Systems. METHODS: A digital 3D model of the patient's cervical spine was rendered from the patients CT data. It was then possible to correct degenerative deformities by digitally repositioning the vertebrae and virtually resecting the osteophytes. The implantation of the cage can be simulated to check the accuracy of the fit. The cage is made of trabecular titanium and manufactured by Direct Metal Printing. RESULTS: The pilot project for the implantation of the first individualized cervical cage ever, resulted in a highly accurate fit. During surgery, the cage self-located into the correct position after suspending distraction due to the implants unique end plate design. Furthermore, it was impossible to move the cage in any direction with the inserting instrument after suspending distraction for the same reason. Thus, it can be assumed that an individualized cervical implant provides excellent primary stability. CONCLUSION: Preconditions for the manufacturing of individualized cervical fusion cages using specific patient data are given. The implantation is uncomplicated. The improved load-bearing surface will lower the rate of implant dislocation and subsidence. The production of individualized cages at a reasonable price has to be evaluated by spine surgeons and the industry.

Reconstruction of the anterior skull base after major trauma or extensive tumour resection.

BACKGROUND: The authors describe their experience with the reconstruction of complex anterior skull base defects after trauma or tumour resection using a "sandwich" technique with pericranial flap, titanium mesh and TachoSil. METHODS: Description of surgical anatomy, surgical technique, indications, limitations, complications, specific perioperative considerations and specific information to give to the patient about surgery and potential risks. A summary of ten key points is given. CONCLUSIONS: After a bifrontal craniotomy and a subfrontal approach, it is possible to achieve a reliable reconstruction of the anterior skull base in a watertight manner by fixing a pericranial flap or a fascia lata graft to the orbital roofs and planum sphenoidale with an individually tailored titanium mesh and closing the frontobasal dura leasion with TachoSil.

Experience with a modular PEEK system for cervical vertebral body replacement.

STUDY DESIGN: A retrospective case series. SUMMARY OF BACKGROUND DATA: The authors present their experience with the ATHLET vertebral body replacement (VBR) system in combination with the TOSCA plating system for the treatment of cervical spondylotic myelopathy. METHODS: Data obtained from 20 cases were reviewed. Corpectomy and VBR with the ATHLET system was performed in all cases. Patients underwent preoperative and postoperative assessment involving the Japanese Orthopedic Association score, Odom criteria, and radiographic studies to determine the position of the implant as well as cervical lordosis. The mean follow-up period was 20 months (16-28 mo). RESULTS: Implantation of the ATHLET VBR itself was uncomplicated in all cases. The adjustment of the implants' height could be done in 2 mm steps. With increasing height of the implant, the angle of lordosis increases comparable with physiological conditions. The authors performed 13 one-level and 7 two-level corpectomies; from the latter group there were 2 revision cases (10%) with implant dislocation. Four cases (20%) of secondary subsidence of the implant were observed radiographs 12 months postoperatively; in all cases treatment remained conservative. Ten patients (50%) had excellent, 4 (30%) good, 2 (10%) satisfactory, and 2 (10%) poor outcome according to Odom criteria. The average improvement of the Japanese Orthopedic Association score was 1.6. All cases achieved osseous fusion without complications, 55% of them had an improvement, and 15% of them had no change of the sagittal contour. CONCLUSIONS: The ATHLET VBR is easy to implant and avoids bone graft site morbidity. Due to a relatively high rate of secondary subsidence of the implant (20%) and secondary dislocation (10%) in combination to a poor to satisfactory outcome according to Odom criteria in 20%, the authors do not recommend the use of this PEEK implant for cervical VBR.

Modified open-door laminoplasty for the surgical treatment of cervical spondylotic myelopathy in elderly patients.

BACKGROUND: The authors describe their experience with a modified version of the standard technique of open-door laminoplasty for the surgical treatment of spondylotic myelopathy in elderly patients with temporary removal of the laminae, extensive decompression, and pre-plating of the laminae beyond the surgical field. METHODS: Description of surgical anatomy, surgical technique, indications, limitations, complications, and specific perioperative considerations, as well as specific information to give to the patient about surgery and potential risks. A summary of ten key points is given. CONCLUSIONS: Transection of the laminae on both sides (temporary laminectomy) and pre-plating of the laminae outside of the surgical field has several advantages: better decompression of the spinal canal and the neuroforamina on both sides, easier undercutting of adjacent vertebral arches for cranio-caudal decompression, and no risk of spinal cord injury by the screwdriver when attaching plates to the laminae.

Surgical management of cervical spondylotic myelopathy - indications for anterior, posterior or combined procedures for decompression and stabilisation.

BACKGROUND: The authors describe their experience with the choice of anterior, posterior and combined approaches for the surgical treatment of spondylotic myelopathy. METHODS: Description of surgical anatomy, surgical technique, indications, limitations, complications, specific perioperative considerations and specific information to give to the patient about surgery and potential risks and a summary of 10 key points is given. CONCLUSIONS: If the disease extends behind the posterior vertebral body and if reestablishing spinal sagittal and coronal balance is an aim, then the anterior approach is the best choice. In cases of predominant posterior spinal cord compression and lordotic configuration the posterior approach should be preferred. Decompression of three or more levels, especially in combination with poor bone quality, requires a combined approach.

Distractable titanium cages versus PEEK cages versus iliac crest bone grafts for the replacement of cervical vertebrae.

OBJECTIVE: To analyse the advantages and disadvantages of distractable titanium cages, polyether-etherketone cages, and iliac crest bone graft for the replacement of cervical vertebral bodies (VBR). METHODS: The clinical and radiological results of 32 patients who underwent cervical corpectomy for the decompression of the spinal canal were retrospectively analysed and discussed. RESULTS: For the vertebral body replacement the authors used distractable titanium cages (n = 6), PEEK cages (n = 19), and iliac crest bone graft (n = 7). The neurological outcomes according to postoperative JOA scores did not show significant differences between the three groups. PEEK cages showed a high rate of secondary subsidence (32%). DISCUSSION: Despite the risk of donor site morbidity the authors recommend iliac crest bone graft as primary choice for VBR because of its excellent fusion rate and its cost effectiveness. For revision cases we recommend titanium cages.

Sub-3-cycle vortex pulses of tunable topological charge.

Novel types of reflective spiral micro-electro-mechanical systems were used to generate few-cycle vortex pulses of variable topological charge from a Ti:sapphire laser oscillator. The phase profile of these components was controlled by varying the temperature. The temporal properties of the pulses were characterized with spatially resolved nonlinear autocorrelation. The beam structure resembles a slightly distorted Laguerre-Gaussian distribution. The different topological charges were indicated by detecting Poynting-vector maps with a programmable Shack-Hartmann sensor of enhanced angular sensitivity.

Lipocalin-2 as mediator of chemokine expression and granulocyte infiltration during ischemia and reperfusion.

Lipocalin-2 (Lcn2) expression contributes to ischemia and reperfusion injury (IRI) by enhancing pro-inflammatory responses. The aim of this work was to elucidate the regulation of Lcn2 during hypoxia and its effects on the expression of key chemokines and adhesion molecules. Lcn2 wt and Lcn2(-/-) mice were used in a heterotopic heart transplantation model. Quantitative RT-PCR was applied for chemokine gene expression analysis. Reporter gene studies were used to elucidate the regulation of the Lcn2 promoter by hypoxia. HIF-1ß expression led to a 2.4-fold induction of the Lcn2 promoter. Apart from an earlier onset of granulocyte infiltration in the Lcn2 wt setting after 2 h of reperfusion compared with the Lcn2(-/-) setting (P < 0.013), exogenous application of recombinant Lcn2 revealed a trend toward increase of granulocyte infiltration. Analyzed chemokines were expressed significantly higher in the Lcn2 wt setting at 2 h of reperfusion (P ≤ 0.05). The number of apoptotic cells observed in Lcn2(-/-) grafts was significantly higher than in the Lcn2 wt setting. Our results indicate that Lcn2 affects granulocyte infiltration in the reperfused graft by modulating the expression of chemokines, their receptors and the apoptotic rate.

Application of Dried Urine Spots for Non-Targeted Quadrupole Time-of-Flight Drug Screening.

The use of dried urine spots (DUS) can simplify sample handling, shipment and storage when compared to liquid urine samples. To prepare DUS, a small amount of urine is pipetted on a filter paper card. The subsequent drying of the specimen can prevent the post-sampling formation or degradation of substances (e.g., caused by bacteria). To evaluate the potential of DUS screening, 17 authentic urine samples, containing a broad range of substances, were extracted and analyzed on a Sciex TripleTOF® 5600+ System using a non-targeted screening and library searching approach. The screening results were compared to the analysis of the same urine sample in liquid form, using the same high-resolution liquid chromatography--quadrupole time-of-flight mass spectrometry method. More than 65 different legal and illegal drugs were successfully identified within the investigated 17 urine samples using the DUS screening approach. When compared to the analysis of liquid urine, the following compounds could not be identified: 1x ecgonine methyl ester, 1x nicotine, 1x promazine and 1x 11-nor-9-carboxy-∆9-tetrahydrocannabinol. Overall, 95.2% of the target substances that have been detected in liquid urine were identified correctly using the DUS approach. In conclusion, DUS screening offers a simple, cost-effective and easier sample handling alternative to the traditional use of liquid urine and provides the detection of the most important substances for forensic requirements. Furthermore, the DUS sample preparation can be fully automated (sample documentation, internal standard application and extraction).

Inhibition of bacterial degradation of EtG by collection as dried urine spots (DUS).

Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are direct alcohol consumption markers widely used nowadays for clinical and forensic applications. They are detectable in blood and urine even after consumption of trace amounts of ethanol and for a longer time frame, being detectable even when no more ethanol is present. The instability of EtG against bacterial degradation in contaminated urine samples and/or the possible postcollection synthesis of this metabolite in samples containing, e.g., Escherichia coli and ethanol, may cause false identification of alcohol uptake. Therefore, it is of paramount importance to constrict these error sources by inhibition of any bacterial growth causing hydrolization or synthesis of EtG. This study evaluates a new method of collecting urine samples on filter paper, dried urine spots (DUS), for simultaneous detection of EtG, EtS and creatinine, having the great advantage of inhibiting bacterial activity. In addition, a method validation for the determination of EtG and EtS in DUS was performed according to the FDA guidelines. Sterile-filtered urine was spiked with EtG and EtS, inoculated with E. coli and incubated. Liquid and dried urine samples were collected after various time intervals up to 96 h. Liquid samples were frozen immediately after collection, whereas aliquots for DUS were pipetted onto filter paper, allowed to dry and stored at RT until analysis 1 week after. The specimens were analyzed by LC-ESI-MS/MS. As expected, degradation of EtG, but not of EtS, was observed in contaminated liquid urine samples. However, the specimens collected on filter paper and stored at RT showed no degradation during storage. Therefore, collecting urine samples on filter paper for EtG and EtS analysis turns out to be a reliable method to avoid bacterial degradation of EtG and EtS, and consequently, stabilization of these ethanol metabolites is achieved. In addition, simultaneous measurement of creatinine content as an indicator of urine dilution helps to interpret the results. Method validation for EtG and EtS in DUS was satisfactory, showing the linearity of the calibration curves in the studied concentration range, good precision, accuracy and selectivity.

On-line SPE LC-MS/MS for the quantification of Δ9-tetrahydrocannabinol (THC) and its two major metabolites in human peripheral blood by liquid chromatography tandem mass spectrometry.

A universal and robust analytical method for the determination of Δ9-tetrahydrocannabinol (THC) and two of its metabolites Δ9-(11-OH)-tetrahydrocannabinol (11-OH-THC) and 11-nor-Δ9-carboxy-tetrahydrocannabinol (THC-COOH) in human whole blood was developed and validated for use in forensic toxicology. Protein precipitation, integrated solid phase extraction and on-line enrichment followed by high-performance liquid chromatography separation and detection with a triple quadrupole mass spectrometer were combined. The linear ranges used for the three cannabinoids were from 0.5 to 20 ng/mL for THC and 11-OH-THC and from 2.5 to 100 ng/mL for THC-COOH, therefore covering the requirements for forensic use. Correlation coefficients of 0.9980 or better were achieved for all three analytes. No relevant hydrolysis was observed for THC-COOH glucuronide with this procedure--in contrast to our previous GC-MS procedure, which obviously lead to an artificial increase of the THC-COOH concentration due to the hydrolysis of the glucuronide-conjugate occurring at high pH during the phase-transfer catalyzed methylation step.