[Intercultural adaptation of the PUKSoPC in German language : A scale for perceived control in patients with Parkinson's disease]. / Interkulturelle Adaptation der PUKSoPC in deutscher Sprache : Eine Skala zur gefühlten Kontrolle von Parkinson-Patientinnen und -Patienten.

BACKGROUND: The level of perceived control in people with Parkinson's disease plays a significant role in affecting their quality of life. Simpson et al. developed a scale of perceived control specific to Parkinson's disease called the Parkinson's UK Scale of Perceived Control (PUKSoPC). In this work, we present a cross-culturally adapted German translation of the original English version. METHODS: After receiving approval by the original authors, an internationally established procedure was used for cross-cultural adaptation. Firstly, the original English version was translated into German independently by two bilingual neuroscientists, who then agreed on a consensus version. This was tested on 10 people with Parkinson's disease and independently back translated into English by two different neuroscientists. After forming a consensus version, this English version was compared with the original version by all four translators. Differences between the versions resulted in modifications to the German translation so that the back translation matched the original as closely as possible. The final version was approved by two of the original authors and clinically tested on 50 people with Parkinson's disease. RESULTS: During the translation process, the four translators agreed on a culturally adapted German version of the PUKSoPC. Testing of the final version on 50 people with Parkinson's disease did not reveal any linguistic or content-related problems. CONCLUSION: The linguistically validated German version of the PUKSoPC presented in this paper is now freely available for measuring the levels of perceived control in people with Parkinson's disease to advance both research and clinical practice.

The Pelvic Girdle Pain deadlock: 2. Topics that, so far, have remained out of focus.

INTRODUCTION: In our preceding paper, we concluded that Pelvic Girdle Pain (PGP) should be taken seriously. Still, we do not know its causes. Literature reviews on treatment fail to reveal a consistent pattern, and there are patients who do not respond well to treatment. We designated the lack of progress in research and in the clinic as 'deadlock', and proposed a 'deconstruction' of PGP, that is to say, taking PGP apart into its relevant dimensions. PURPOSE: We examine the proposition that PGP may emerge as local inflammation. Inflammation would be a new dimension to be taken into account, between biomechanics and psychology. To explore the consequences of this idea, we present four different topics that, so far, have remained out of focus. One: The importance of microtrauma. Two: Ways to counteract chronification. Three: The importance of sickness behaviour when systemic inflammation turns into neuroinflammation of the brain. And Four: The mainly emotional and cognitive nature of chronic pain, and how aberrant neuroinflammation may render chronic pain intractable. For intractable pain, sleep and stress management are promising treatment options. IMPLICATIONS: The authors hope that the present paper helps to stimulate the flexible creativity that is required to deal with the biological and psychological impact of PGP. Measuring inflammatory mediators in PGP should be a research priority. It should be understood that the boundaries between biology and psychology are becoming blurred. Clinicians must frequently monitor pain, disability, and mood, and be ready to switch treatment whenever the patient does not improve.

Respiratory and hemodynamic perioperative adverse events in intravenous versus inhalational induction in pediatric anesthesia: A systematic review and meta-analysis.

Perioperative respiratory and hemodynamic adverse events are still a cause of morbidity and mortality in pediatric anesthesia. It has been suggested that volatile agents might be associated with more respiratory adverse events compared to intravenous agents (eg, propofol), which have been associated with a higher risk of bradycardia compared to volatile agents. We performed a systematic review and meta-analysis to evaluate the risk of perioperative hemodynamic and respiratory adverse events, comparing intravenous induction with inhalational induction in pediatric anesthesia. We searched PubMed, Embase, and Medline up to February 12, 2020. Randomized controlled trials were included. A quality assessment was carried out using a modified version of the "Cochrane Risk of Bias Tool for Randomized Controlled Trials." Of the 1602 applicable publications, four were included in the final review. Two studies found no significant differences in perioperative respiratory or hemodynamic adverse events. Two studies found a higher risk of respiratory perioperative adverse events in inhalation versus intravenous induction, with a relative risk varying from 1.64 to 3.83. Data were heterogenous, and pooled estimates may not be reliable. The present systematic review and meta-analysis revealed no significant difference in the occurrence of perioperative respiratory adverse events between inhalation and intravenous induction. More respiratory adverse events during and after inhalation induction were found, in particular in children with multiple risk factors for respiratory adverse events. This did not reach significance. Future research should include a large randomized controlled trial comparing inhalation and intravenous induction with respiratory and hemodynamic adverse events as primary outcome and adequately blinded outcome assessors.

Blocking substance P signaling reduces musculotendinous and dermal fibrosis and sensorimotor declines in a rat model of overuse injury.

Purpose/Aim: Substance P-NK-1R signaling has been implicated in fibrotic tendinopathies and myositis. Blocking this signaling with a neurokinin 1 receptor antagonist (NK1RA) has been proposed as a therapeutic target for their treatment.Materials and Methods: Using a rodent model of overuse injury, we pharmacologically blocked Substance P using a specific NK1RA with the hopes of reducing forelimb tendon, muscle and dermal fibrogenic changes and associated pain-related behaviors. Young adult rats learned to pull at high force levels across a 5-week period, before performing a high repetition high force (HRHF) task for 3 weeks (2 h/day, 3 days/week). HRHF rats were untreated or treated in task weeks 2 and 3 with the NK1RA, i.p. Control rats received vehicle or NK1RA treatments.Results: Grip strength declined in untreated HRHF rats, and mechanical sensitivity and temperature aversion increased compared to controls; these changes were improved by NK1RA treatment (L-732,138). NK1RA treatment also reduced HRHF-induced thickening in flexor digitorum epitendons, and HRHF-induced increases of TGFbeta1, CCN2/CTGF, and collagen type 1 in flexor digitorum muscles. In the forepaw upper dermis, task-induced increases in collagen deposition were reduced by NK1RA treatment.Conclusions: Our findings indicate that Substance P plays a role in the development of fibrogenic responses and subsequent discomfort in forelimb tissues involved in performing a high demand repetitive forceful task.

Calcium Fluxes in Work-Related Muscle Disorder: Implications from a Rat Model.

INTRODUCTION: Ca2+ regulatory excitation-contraction coupling properties are key topics of interest in the development of work-related muscle myalgia and may constitute an underlying cause of muscle pain and loss of force generating capacity. METHOD: A well-established rat model of high repetition high force (HRHF) work was used to investigate if such exposure leads to an increase in cytosolic Ca2+ concentration ([Ca2+]i) and changes in sarcoplasmic reticulum (SR) vesicle Ca2+ uptake and release rates. RESULT: Six weeks exposure of rats to HRHF increased indicators of fatigue, pain behaviors, and [Ca2+]i, the latter implied by around 50-100% increases in pCam, as well as in the Ca2+ handling proteins RyR1 and Casq1 accompanied by an ∼10% increased SR Ca2+ uptake rate in extensor and flexor muscles compared to those of control rats. This demonstrated a work-related altered myocellular Ca2+ regulation, SR Ca2+ handling, and SR protein expression. DISCUSSION: These disturbances may mirror intracellular changes in early stages of human work-related myalgic muscle. Increased uptake of Ca2+ into the SR may reflect an early adaptation to avoid a sustained detrimental increase in [Ca2+]i similar to the previous findings of deteriorated Ca2+ regulation and impaired function in fatigued human muscle.

Directional DBS leads show large deviations from their intended implantation orientation.

OBJECTIVE: Lead orientation is a new degree of freedom with directional deep brain stimulation (DBS) leads. We investigated how prevalent deviations from the intended implantation direction are in a large patient cohort. METHODS: The Directional Orientation Detection (DiODe) algorithm to determine lead orientation from postoperative CT scans was implemented into the open-source Lead-DBS toolbox. Lead orientation was analyzed in 100 consecutive patients (198 leads). Different anatomical targets and intraoperative setups were compared. RESULTS: Deviations of up to 90° from the intended implantation direction were observed. Deviations of more than 30° were seen in 42% of the leads and deviations of more than 60° in about 11% of the leads. Deviations were independent from the neuroanatomical target and the stereotactic frame but increased depending on which microdrive was used. DISCUSSION: Our results indicate that large deviations from the intended implantation direction are a common phenomenon in directional leads. Postoperative determination of lead orientation is thus mandatory for investigating directional DBS.

Beneficial effects of bilateral subthalamic stimulation on alexithymia in Parkinson's disease.

BACKGROUND AND PURPOSE: Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL) and motor and non-motor symptoms in advanced Parkinson's disease (PD). However, its effect on alexithymia and its relationship to other neuropsychiatric symptoms and QoL in PD is unclear. METHODS: In this prospective, observational study of 39 patients with PD undergoing STN-DBS, we examined the Parkinson's Disease Questionnaire-8 (PDQ-8), 20-item Toronto Alexithymia Scale (TAS-20), Hospital Anxiety and Depression Scale (HADS), Self-Report Manic Inventory (SRMI), Apathy Evaluation Scale (AES), Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living, UPDRS motor examination and UPDRS complications (UPDRS-II/-III/-IV) and levodopa-equivalent daily dose (LEDD) pre-operatively and at 5-month follow-up. Outcome changes were tested with Wilcoxon signed-rank or paired t-test when parametric tests were applicable and corrected for multiple comparisons. The relationship between outcome changes was explored with bivariate correlations. Additionally, partial correlations between PDQ-8 and TAS-20 were computed controlling for HADS, SRMI and AES change scores. Predictor analyses for PDQ-8 improvement were calculated for all baseline parameters. RESULTS: The baseline prevalence of alexithymia was 17.9%. We observed significant beneficial effects of STN-DBS on PDQ-8, TAS-20, HADS, UPDRS-II, -III and -IV scores and significant LEDD reduction. The correlation between TAS-20 and PDQ-8 improvements remained significant after controlling for all other aforementioned outcomes. Predictor analyses for PDQ-8 improvement were significant for PDQ-8 and TAS-20. CONCLUSIONS: This is the first report of beneficial effects of STN-DBS on alexithymia. Alexithymia was significantly associated with QoL outcome independent of anxiety, depression, mania and apathy. Our study highlights the importance of alexithymia for holistic assessments of DBS outcomes.

Macintosh Blade Videolaryngoscopy Combined With Rigid Bonfils Intubation Endoscope Offers a Suitable Alternative for Patients With Difficult Airways.

BACKGROUND: In the armamentarium of an anesthesiologist, videolaryngoscopy is a valuable addition to secure the airway. However, when the videolaryngoscope (VLS) offers no solution, few options remain. Earlier, we presented an intubation technique combining Macintosh blade VLS and Bonfils intubation endoscope (BIE) for a patient with a history of very difficult intubation. In the present study, we evaluated this technique to establish whether it is a valuable alternative. METHODS: In this single-blinded nonrandomized study, 38 patients with a history of difficult intubation or 1 or more predictors of difficult intubation, scoring a Cormack & Lehane (C&L) grade III or IV using Macintosh blade VLS, were included. Patients were intubated combining the VLS with the BIE. The C&L grade was scored 3 times during (1) direct laryngoscopy; (2) indirect videolaryngoscopy; and (3) using the combined technique (VLS + BIE). Afterward, 2 blinded anesthesiologists assessed the C&L grade using the pictures taken during the procedure. RESULTS: Data of 38 patients were analyzed. An improvement of the C&L grade with the combined technique occurred in 33 of 38 patients (86.8%; 95% confidence interval, 71.9%-95.6%). Reviewer 1 reported an improvement of the C&L grade with the combined technique in 37 of 38 patients. Reviewer 2 reported improvement in 33 and deterioration in 2 of the patients. No complications occurred. CONCLUSIONS: The combined use of a VLS with Macintosh blade and BIE gives the anesthesiologist a valuable alternative intubation option in patients with extremely difficult airways.

Effectiveness of conservative interventions for sickness and pain behaviors induced by a high repetition high force upper extremity task.

BACKGROUND: Systemic inflammation is known to induce sickness behaviors, including decreased social interaction and pain. We have reported increased serum inflammatory cytokines in a rat model of repetitive strain injury (rats perform an upper extremity reaching task for prolonged periods). Here, we sought to determine if sickness behaviors are induced in this model and the effectiveness of conservative treatments. METHODS: Experimental rats underwent initial training to learn a high force reaching task (10 min/day, 5 days/week for 6 weeks), with or without ibuprofen treatment (TRHF vs. TRHF + IBU rats). Subsets of trained animals went on to perform a high repetition high force (HRHF) task for 6 or 12 weeks (2 h/day, 3 days/week) without treatment, or received two secondary interventions: ibuprofen (HRHF + IBU) or a move to a lower demand low repetition low force task (HRHF-to-LRLF), beginning in task week 5. Mixed-effects models with repeated measures assays were used to assay duration of social interaction, aggression, forepaw withdrawal thresholds and reach performance abilities. One-way and two-way ANOVAs were used to assay tissue responses. Corrections for multiple comparisons were made. RESULTS: TRHF + IBU rats did not develop behavioral declines or systemic increases in IL-1beta and IL-6, observed in untreated TRHF rats. Untreated HRHF rats showed social interaction declines, difficulties performing the operant task and forepaw mechanical allodynia. Untreated HRHF rats also had increased serum levels of several inflammatory cytokines and chemokines, neuroinflammatory responses (e.g., increased TNFalpha) in the brain, median nerve and spinal cord, and Substance P and neurokinin 1 immunoexpression in the spinal cord. HRHF + IBU and HRHF-to-LRLF rats showed improved social interaction and reduced inflammatory serum, nerve and brain changes. However, neither secondary treatment rescued HRHF-task induced forepaw allodynia, or completely attenuated task performance declines or spinal cord responses. CONCLUSIONS: These results suggest that inflammatory mechanisms induced by prolonged performance of high physical demand tasks mediate the development of social interaction declines and aggression. However, persistent spinal cord sensitization was associated with persistent behavioral indices of discomfort, despite use of conservative secondary interventions indicating the need for prevention or more effective interventions.

Safe and prolonged survival with long-term exposure to pomalidomide in relapsed/refractory myeloma.

BACKGROUND: The IFM2009-02 trial studied pomalidomide (4 mg daily, 21/28 versus 28/28) and dexamethasone in very advanced relapsed or refractory multiple myeloma (RRMM). We observed that 40% of patients had a prolonged progression-free survival (PFS) and subsequently overall survival (OS). We sought to analyze the characteristics of these patients and study the effect of long exposure to pomalidomide. DESIGN: We separated the studied population into two groups: 3 months to 1 year (<1 year) and more than 1 year (≥1 year) of treatment with pomalidomide and dexamethasone based on clinical judgment and historical control studies. We then analyzed the characteristics of patients according to duration of treatment. RESULTS: The overall response rate (ORR) for the <1-year group was 43%, the median PFS 4.6 months [95% confidence interval (95% CI) 3.8-6.4] with only 6% at 12 months, and the median OS was 15 months (11.7-20.3) and 40% at 18 months. For the ≥1-year group, the response rate and survival were strikingly different, ORR at 83%, median PFS 20.7 months (14.7-35.4), median OS not reached, and 91% at 18 months. CONCLUSION: Pomalidomide and dexamethasone favored prolonged and safe exposure to treatment in 40% of heavily treated and end-stage RRMM, a paradigm shift in the natural history of RRMM characterized with a succession of shorter disease-free intervals and ultimately shorter survival. Although an optimization of pomalidomide-dexamethasone regimen is warranted in advanced RRMM, we claim that pomalidomide has proven once more to change the natural history of myeloma in this series, which should be confirmed in a larger study.

Acid ceramidase treatment enhances the outcome of autologous chondrocyte implantation in a rat osteochondral defect model.

OBJECTIVE: The overall aim of this study was to evaluate how supplementation of chondrocyte media with recombinant acid ceramidase (rhAC) influenced cartilage repair in a rat osteochondral defect model. METHODS: Primary chondrocytes were grown as monolayers in polystyrene culture dishes with and without rhAC (added once at the time of cell plating) for 7 days, and then seeded onto Bio-Gide® collagen scaffolds and grown for an additional 3 days. The scaffolds were then introduced into osteochondral defects created in Sprague-Dawley rat trochlea by a microdrilling procedure. Analysis was performed 6 weeks post-surgery macroscopically, by micro-CT, histologically, and by immunohistochemistry. RESULTS: Treatment with rhAC led to increased cell numbers and glycosaminoglycan (GAG) production (∼2 and 3-fold, respectively) following 7 days of expansion in vitro. Gene expression of collagen 2, aggrecan and Sox-9 also was significantly elevated. After seeding onto Bio-Gide®, more rhAC treated cells were evident within 4 h. At 6 weeks post-surgery, defects containing rhAC-treated cells exhibited more soft tissue formation at the articular surface, as evidenced by microCT, as well as histological evidence of enhanced cartilage repair. Notably, collagen 2 immunostaining revealed greater surface expression in animals receiving rhAC treated cells as well. Collagen 10 staining was not enhanced. CONCLUSION: The results further demonstrate the positive effects of rhAC treatment on chondrocyte growth and phenotype in vitro, and reveal for the first time the in vivo effects of the treated cells on cartilage repair.

Underdevelopment of trabecular bone microarchitecture in the distal femur of nonambulatory children with cerebral palsy becomes more pronounced with distance from the growth plate.

SUMMARY: We found that the underdeveloped trabecular bone microarchitecture in the distal femur of children with cerebral palsy (CP) who are unable to ambulate independently becomes more pronounced with increased distance from the growth plate. This suggests that the degree of underdevelopment in trabecular bone in children with CP is greater than previously understood. INTRODUCTION: Children with CP who are unable to ambulate independently have severely underdeveloped trabecular bone microarchitecture in the distal femur. The aim of the study was to determine if the level of underdevelopment in trabecular bone microarchitecture is consistent across the distal femur in children with CP. METHODS: Children with quadriplegic CP and typically developing children were studied (n=12/group, 5-14 years). Apparent bone volume to total volume (appBV/TV), trabecular number (appTb.N), trabecular thickness (appTb.Th), and trabecular separation (appTb.Sp) were estimated in each of 20 magnetic resonance images collected above the growth plate in the distal femur. RESULTS: For the total region, appBV/TV, appTb.N, and appTb.Th were lower (30, 21, and 12%, respectively) and appTb.Sp was higher (52%) (all p≤0.001) in children with CP than in controls. Distance from the growth plate was inversely related to appBV/TV and appTb.N and was positively related to appTb.Sp at the same distance in children with CP and controls (all p<0.01). However, the relationships were stronger (r2=0.87 to 0.92 versus 0.36 to 0.65) and the slopes were steeper in children with CP (all p<0.01). Furthermore, the steepness of the slopes in children with CP was positively related to appBV/TV, appTb.N, appTb.Th, and appTb.Sp for the total region (r2=0.37 to 0.75, p<0.05). CONCLUSIONS: The underdeveloped trabecular bone microarchitecture in the metaphysis of the distal femur in children with CP becomes more pronounced with greater distance from the growth plate. This pattern is most profound in children with the least developed trabecular bone microarchitecture.

Cognitive training in Parkinson's disease reduces cognitive decline in the long term.

BACKGROUND AND PURPOSE: Patients with Parkinson's disease (PD) are at high risk for cognitive dysfunction. Non-pharmacological interventions have attracted increasing interest for enhancing PD patients' cognitive functions. METHODS: One-year follow-up data (T2 ) of a randomized controlled trial evaluating two 6-week cognitive trainings - a structured (NEUROvitalis, NV) and an unstructured (mentally fit, MF) program - compared with a waiting list control group (CG) in non-demented PD patients (Hoehn and Yahr I-III) are presented. Forty-seven PD patients were examined at T2 . Effects on overall cognitive functions (Mini-Mental State Examination and DemTect) were compared between all groups with repeated measurement analyses of variance. A combined score of the percentage change value from baseline (T0 ) to T2 was calculated to identify patients who retained or improved their cognitive state (responders). The risk of developing mild cognitive impairment (MCI) was analyzed. RESULTS: Significant time × treatment effects on overall cognitive functions were found for both training groups, each compared separately to the CG (DemTect, P < 0.05). Nine patients (56.3%) of the NV group, seven (41.2%) of the MF group and three (21.4%) of the CG were responders. Comparing NV to CG the odds ratio was 4.7 [95% confidence interval (0.8; 33.3)], and comparing MF to CG it was 2.6 [95% confidence interval (0.4; 17.4)]. MCI risk for patients without prior MCI was 40.0% in CG, 18.2% in MF and 18.2% in NV. The odds ratio was 3 comparing NV to CG, MF to CG. DISCUSSION: This study gives evidence that cognitive training may be effective to prevent cognitive decline and onset of MCI in PD patients.

Gross anatomical study of the nerve supply of genitourinary structures in female mongrel hound dogs.

Anatomical variations in lumbosacral plexus or nerves to genitourinary structures in dogs are under described, despite their importance during surgery and potential contributions to neuromuscular syndromes. Gross dissection of 16 female mongrel hound dogs showed frequent variations in lumbosacral plexus classification, sympathetic ganglia, ventral rami input to nerves innervating genitourinary structures and pudendal nerve (PdN) branching. Lumbosacral plexus classification types were mixed, rather than pure, in 13 (82%) of dogs. The genitofemoral nerve (GFN) originated from ventral ramus of L4 in 67% of nerves, differing from the expected L3. Considerable variability was seen in ventral rami origins of pelvic (PN) and Pd nerves, with new findings of L7 contributions to PN, joining S1 and S2 input (23% of sides in 11 dogs) or S1-S3 input (5%), and to PdN, joining S1-S2, unilaterally, in one dog. L7 input was confirmed using retrograde dye tracing methods. The PN also received CG1 contributions, bilaterally, in one dog. The PdN branched unusually in two dogs. Lumbosacral sympathetic ganglia had variant intra-, inter- and multisegmental connectivity in 6 (38%). Thus, the anatomy of mongrel dogs had higher variability than previously described for purebred dogs. Knowledge of this variant innervation during surgery could aid in the preservation of nerves and reduce risk of urinary and sexual dysfunctions.

Staphylococcus caprae bone and joint infections: a re-emerging infection?

Staphylococcus caprae has been recently classified as a human pathogen, but the incidence of S. caprae in human bone and joint infections (BJIs) is under-reported. In this study, we report 25 cases of S. caprae BJI, and we review the 31 cases published in the literature. Molecular techniques and matrix-assisted laser desorption ionization time-of-flight mass spectrometry improved the identification of clinically relevant S. caprae strains. In this study, 96% of S. caprae BJIs were localized to the lower limbs, and 88% of the cases involved orthopaedic device infections. S. caprae joint prosthesis infections (JPIs), internal osteosynthesis device infections (I-ODIs) and BJIs without orthopaedic device infections were recorded in 60%, 28% and 12% of cases, respectively. Ten (40%) S. caprae BJIs were polymicrobial infections. These infections were associated with past histories of malignancy (p 0.024). Of the 14 bacterial species related to S. caprae BJI, 57% were staphylococci. I-ODIs were significantly associated with polymicrobial infections (p 0.0068), unlike JPIs, which were monomicrobial infections (p 0.0344). Treatment with rifampicin and fluoroquinolone was recorded in 40% of cases. Surgical treatment was performed in 76% of cases, e.g. prosthesis removal (36%), osteosynthesis device removal (24%), and surgical debridement (16%). Thirty per cent of cases were not treated. Relapses were observed mainly in the patients treated by surgical debridement only (p 0.033). In summary, S. caprae BJI is an underestimated hospital-acquired emerging infection. S. caprae BJI is correlated with infections in orthopaedic devices, which must be removed to control the infection.