Use of natural medicine and dietary supplements concomitant with conventional medicine among people with Multiple Sclerosis.

BACKGROUND: The use of complementary and alternative medicine (CAM) are widespread among people with Multiple Sclerosis (PwMS) and are often used concomitant with conventional treatment. Natural medicine and dietary supplements (NADS) are the most frequently used CAM modality and among other patient groups use of NADS concomitant with conventional medicine has been reported as a potential risk to patients' safety due to risk of drug interactions. The use of NADS concomitant with conventional medicine has, however, not been investigated among PwMS. This study's aim was to investigate the prevalence of NADS and conventional MS-related medicine use among PwMS, specific types of NADS and conventional MS-related medicine used, the prevalence of NADS used concomitant with conventional MS-related medicine, and to characterize PwMS who use NADS and PwMS who use NADS concomitant with conventional MS-related medicine in a Danish context. METHODS: The study was a cross-sectional study conducted as an interviewer-administered survey via phone in April 2019. The questionnaire includes questions about the use of NADS and conventional MS medicine as well as sociodemographic and health-related factors. In total 384 PwMS answered the questionnaire. Both descriptive and logistic analyses were used to analyze the data. RESULTS: The results show that the majority of PwMS use conventional MS-related medicine. In total, 85 % (n=322) had used at least one NADS within the last 12 months including vitamin D. When excluding vitamin D, the use of NADS within the last 12 months was 78.4% (n=298). Beside vitamin D the most reported types of NADS used were fatty acids (37%), Multivitamins (37%), and Calcium (35%). A total of 75.8% (n=288) reported using NADS concomitant with conventional MS medicine, and the products most often combined with conventional MS medicine were Vitamin D, Multivitamin, Calcium, Magnesium, and fatty acids. The results suggest that PwMS using NADS concomitant with conventional MS-related medicine are characterized by a high prevalence of young and newly diagnosed patients with a high education level. CONCLUSION: The study contributes to a better understanding of NADS used among PwMS. The study shows that the majority of PwMS use NADS and that they use it concomitant with conventional MS-medicine. Furthermore, the detailed mapping of the specific types of NADS used gives a nuanced insight into the specific products of NADS used among PwMS, including different kinds of vitamins, minerals, and herbal remedies.

The socio-material self-care practices of children living with hemophilia or juvenile idiopathic arthritis in Denmark.

Growing up with a chronic disease can take its toll on children and their families, and if poorly managed, be disruptive to children's long-term health and wellbeing. While parents and health service providers do play a central role in disease management, children's own self-care practices often go unnoticed. In existing literature, children's self-care practices only tend to emerge in research with adolescents who "transition" from pediatric to adult clinical care services. This study was conducted in December 2017 to May 2018 and explores ethnographically the self-care practices of children affected by hemophilia or juvenile idiopathic arthritis in Denmark, with a particular interest in how social relations and material context affect their pre-transition self-care practices. A total number of 16 children and adolescents aged 7-17 years and 39 family members participated in the study. We find that the children participate in three socio-material self-care practices. Firstly, the children actively engage in home treatment of their bodies by changing the setup of medical equipment and incorporating everyday materialities to make treatment more comfortable. Secondly, they play games imitating their own treatment, using medical equipment on dolls or teddy bears to seek out experience and learning. Thirdly, they seek a sense of normality by tactically hiding material signifiers of their disease in online and offline encounters with peers. Our findings suggest that children living with a chronic disease establish and participate in a range of different self-care practices, and actively mobilize people and things around them to achieve precisely this. We conclude that these socio-material self-care practices are central to helping children make sense of living with chronic disease, both to maintain health and wellbeing, but also to gain greater independence. We encourage others to recognize children's pre-transition self-care practices, and the implications of these agentic capabilities.

Increased serum levels of sortilin are associated with depression and correlated with BDNF and VEGF.

Neurotrophic factors have been investigated in relation to depression. The aim of the present study was to widen this focus to sortilin, a receptor involved in neurotrophic signalling. The serum sortilin level was investigated in 152 individuals with depression and 216 control individuals, and eight genetic markers located within the SORT1 gene were successfully analysed for association with depression. Genotyping was performed using the Sequenom MassARRAY platform. All the individuals returned a questionnaire and participated in a semi-structured diagnostic interview. Sortilin levels were measured by immunoassay, and potential determinants of the serum sortilin level were assessed by generalized linear models. Serum levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were measured in previous studies. We identified a significant increase of serum sortilin levels in depressed individuals compared with controls (P=0.0002) and significant positive correlation between serum sortilin levels and the corresponding levels of BDNF and VEGF. None of the genotyped SNPs were associated with depression. Additional analyses showed that the serum sortilin level was influenced by several other factors. Alcohol intake and body mass index, as well as depression, serum BDNF and serum VEGF were identified as predictors of serum sortilin levels in our final multivariate model. In conclusion, the results suggest a role of circulating sortilin in depression which may relate to altered activity of neurotrophic factors.

SorCS3 does not require propeptide cleavage to bind nerve growth factor.

The functional properties of the Vps10p-domain receptor SorCS3 are undescribed. Here, we examine its processing and sorting in cellular transfectants, and analyze the binding of potential ligands to the purified receptor. We show that SorCS3 is synthesized as a proprotein and converted to its mature form by N-terminal propeptide cleavage in distal Golgi compartments. The propeptide is not a requirement for normal processing of the receptor and does not prevent ligands from binding to the SorCS3 precursor form. Expression of wt and chimeric receptors further suggests that SorCS3 predominates on the plasma membrane, exhibits slow internalization and does not engage in intracellular trafficking. SorCS3 emerges as a new neurotrophin binding Vps10p-domain receptor functionally distinct from its relatives Sortilin and SorLA.

Reliability of assessing end-feel and pain and resistance sequence in subjects with painful shoulders and knees.

STUDY DESIGN: Descriptive. OBJECTIVES: Examine the intrarater and interrater reliability of end-feel and pain/resistance sequence for patients with painful shoulders and knees. BACKGROUND: Clinicians make diagnostic and intervention decisions based on end-feel and pain/resistance sequence, but few studies have examined agreement within and between physical therapists when assessing subjects with pathology. METHODS AND MEASURES: Subjects with unilateral knee pain (18 men and 22 women with a mean age of 31.8 +/- 9.5 years) or shoulder pain (21 men and 25 women with a mean age of 34.3 +/- 12.9 years) were examined twice. Two physical therapists used standardized positions to evaluate 2 knee motions and 5 shoulder motions. Evaluators did not interview subjects and were blinded to previous test results. Evaluators applied overpressure and noted the end-feel while subjects identified the moment their pain was reproduced. Following testing, subjects rated their pain intensity. Analyses included: percentage of agreement; kappa, weighted kappa, and maximum kappa coefficients; and confidence intervals. Analyses were repeated for subjects whose pain intensity during testing did not change between examinations. RESULTS: Intrarater kappa coefficients varied from 0.65 to 1.00 for end-feel, and intrarater weighted kappa coefficients varied from 0.59 to 0.87 for pain/resistance sequence. Most coefficients remained stable or improved for the unchanged subjects. Interrater kappa coefficients for end-feel and weighted kappa coefficients for pain/resistance sequence varied from -0.01 to 0.70. End-feel kappa coefficients remained low for the unchanged subjects, but pain/resistance sequence weighted kappa coefficients improved. Unbalanced distribution affected many coefficients, producing low coefficients even when the percentage of agreement was high. CONCLUSIONS: The appropriate use of end-feel and pain/resistance sequence data requires reliable data gathering, especially when patients are managed by more than one physical therapist. Intrarater reliability of end-feel and pain/resistance judgments at the knee and shoulder were generally good, especially after accounting for subject change and unbalanced distributions. Interrater reliability, however, was generally not acceptable, even after accounting for these factors.

The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein.

Sortilin belongs to a growing family of multiligand type-1 receptors with homology to the yeast receptor Vps10p. Based on structural features and sortilin's intracellular predominance, we have proposed it to be a sorting receptor for ligands in the synthetic pathway as well as on the cell membrane. To test this hypothesis we examine here the cellular trafficking of chimeric receptors containing constructs of the sortilin tail. We report that sorting signals conforming to YXX and dileucine motifs mediate rapid endocytosis of sortilin chimeras, which subsequently travel to the trans-Golgi network, showing little or no recycling. Furthermore, we found that cation-independent mannose 6-phosphate receptor (MPR300)-sortilin chimeras, expressed in mannose 6-phosphate receptor knockout cells, were almost as efficient as MPR300 itself for transport of newly synthesized beta-hexosaminidase and beta-glucuronidase to lysosomes, and established that the sortilin tail contains potent signals for Golgi-endosome sorting. Finally, we provide evidence suggesting that sortilin is the first example of a mammalian receptor targeted by the recently described GGA family of cytosolic sorting proteins, which condition the Vps10p-mediated sorting of yeast carboxypeptidase Y.

Pharmacological properties of the mouse neurotensin receptor 3. Maintenance of cell surface receptor during internalization of neurotensin.

We recently reported the molecular identification of a new type of receptor for the neuropeptide neurotensin (NT), the neurotensin receptor 3 (NTR3), identical to sortilin, which binds receptor-associated protein. Here, we demonstrate that the cloned mouse NTR3 is expressed on the plasma membrane of transfected COS-7 cells. The mouse NTR3 is detectable by photoaffinity labeling and immunoblotting at the cell surface as a 100 kDa N-glycosylated protein. Biochemical analysis and confocal microscopic imaging clearly indicate that NT is efficiently internalized after binding to NTR3, and that despite this internalization, the amount of receptor present on the cell surface is maintained.

Activation and functional characterization of the mosaic receptor SorLA/LR11.

We previously isolated and sequenced the approximately 250-kDa type 1 receptor sorLA/LR11, a mosaic protein with elements characterizing the Vps10p domain receptor family as well as the low density lipoprotein receptor family. The N terminus of the Vps10p domain comprises a consensus sequence for cleavage by furin ((50)RRKR(53)) that precedes a truncation found in sorLA isolated from human brain. Here we show that sorLA, like sortilin-1/neurotensin receptor-3, whose lumenal domain consists of a Vps10p domain only, is synthesized as a proreceptor that is cleaved by furin in late Golgi compartments. We show that the truncation conditions the Vps10p domain for propeptide inhibitable binding of neuropeptides and the receptor-associated protein. We further demonstrate that avid binding of the receptor-associated protein, apolipoprotein E, and lipoprotein lipase not inhibited by propeptide occurs to sites located in other lumenal domains. In transfected cells, about 10% of full-length sorLA were expressed on the cell surface capable of mediating endocytosis. However, the major pool of receptors was found in late Golgi compartments, suggesting possible interaction with newly synthesized ligands. The results show that sorLA, following activation by truncation, binds multiple ligands and may mediate both endocytosis and sorting.

Construct validity of Cyriax's selective tension examination: association of end-feels with pain at the knee and shoulder.

STUDY DESIGN: Descriptive. OBJECTIVES: To examine the relationship between pain and normal and abnormal-pathologic end-feels during passive physiologic motion assessment at the knee and shoulder. We theorized that abnormal-pathologic end-feels would be more painful than normal end-feels. BACKGROUND: End-feel testing and pain intensity information are part of physical therapy musculoskeletal patient examinations. End-feels are categorized as normal or abnormal-pathologic. No previous studies have examined the relationship between pain during end-feel testing and the type of end-feel. METHODS AND MEASURES: Two physical therapists examined subjects with unilateral knee or shoulder pain. Each subject was examined twice. Passive physiologic motions, 2 at the knee and 5 at the shoulder, were tested by applying an overpressure at the end of range of motion using standardized positions. Subjects reported the amount of pain (0-10) immediately after the evaluator recorded the end-feel. Analyses included one-way ANOVAs and post-hoc Tukey's Honestly Significant Difference tests. RESULTS: Some abnormal-pathologic end-feels were significantly more painful than the normal end-feels at both the knee and the shoulder for all physiologic motions. Among the abnormal-pathologic end-feel categories there were no statistical differences in pain intensity, although small samples in some categories may be responsible for this finding. CONCLUSION: Abnormal-pathologic end-feels are associated with more pain than normal end-feels during passive physiologic motion testing at the knee or shoulder. Dysfunction should be suspected when abnormal-pathologic end-feels are present.

Reliability of cervical range of motion using the OSI CA 6000 spine motion analyser on asymptomatic and symptomatic subjects.

Cervical range of motion (ROM) is evaluated in both clinical and research settings. This study's purpose was to determine if ROM data obtained with the OSI CA 6000 Spine Motion Analyser (SMA) from asymptomatic and symptomatic cervical subjects were reliable within and between testers. Cervical ROM was measured in all three planes in 30 adult asymptomatic and 20 adult symptomatic subjects. A standardized protocol was used to fit each subject with the OSI SMA cervical hardware. Subjects were tested in a seated position with the trunk stabilized. Subjects performed four trials of each pain-free cervical motion during testing. The hardware was completely removed and replaced by the same tester and ROM trials in all three planes were repeated for intratester asymptomatic and symptomatic reliability. The same procedure was completed by a second tester for asymptomatic intratester and intertester reliability. Repeated measures analysis of variance and intraclass correlation coefficients (ICC [2,1 and 2 k]) were used to analyse intra- and intertester reliability data. Intratester ICCs were 0.85 or higher (except for flexion 0.76) for asymptomatic subjects and 0. 87 or higher (except for flexion 0.68) for symptomatic subjects for all motions. Intertester ICCs were 0.88 or higher for all motions. Standard error of measurements were less than 3.92 degrees for all motions. Measures of cervical spinal ROM obtained with the OSI SMA showed good intertester reliablity for all motions, and good intratester reliability for all motions with the exception of the motion of flexion for one of the examiners, which showed moderate reliability.