[Rare diseases in the differential diagnosis of myalgia]. / Seltene Erkrankungen in der Differenzialdiagnose bei Myalgien.

Myalgia describes pain in the skeletal muscles. According to the current German clinical guidelines from 2020 (AWMF register number: 030/051), the initial diagnostic assessment consists of the anamnesis, clinical examination, electrophysiological examination and standard laboratory tests. Additional special examinations, such as molecular genetic investigations, special laboratory tests, medical imaging and muscle biopsy are only needed in certain cases. This article focuses on rare neurological diseases that are classically associated with myalgia. In this context etiologically different diseases are considered, whereby some genetically linked diseases (fascioscapulohumeral dystrophy, FSHD, dystrophia myotonica, McArdle's disease, Pompe's disease, limb girdle muscular dystrophy) are contrasted with diseases with an (auto)immune-related pathogenesis (stiff-person syndrome, Isaacs syndrome). The aspects relevant for the diagnosis are particularly highlighted. The therapeutic aspects of the diseases are not part of this article.

[Rare diseases in the differential diagnosis of myalgia]. / Seltene Erkrankungen in der Differenzialdiagnose bei Myalgien.

Myalgia describes pain in the skeletal muscles. According to the current German clinical guidelines from 2020 (AWMF register number: 030/051), the initial diagnostic assessment consists of the anamnesis, clinical examination, electrophysiological examination and standard laboratory tests. Additional special examinations, such as molecular genetic investigations, special laboratory tests, medical imaging and muscle biopsy are only needed in certain cases. This article focuses on rare neurological diseases that are classically associated with myalgia. In this context etiologically different diseases are considered, whereby some genetically linked diseases (fascioscapulohumeral dystrophy, FSHD, dystrophia myotonica, McArdle's disease, Pompe's disease, limb girdle muscular dystrophy) are contrasted with diseases with an (auto)immune-related pathogenesis (stiff-person syndrome, Isaacs syndrome). The aspects relevant for the diagnosis are particularly highlighted. The therapeutic aspects of the diseases are not part of this article.

Crenobalneotherapy for low back pain: systematic review of clinical trials.

Crenobalneotherapy is a treatment commonly used in Europe and Middle East. It uses mineral water sometimes combined with different hydrotherapy techniques. Most patients treated in spa centers suffer from low back pain. The purpose of this work is to identify clinical trials on crenobalneotherapy for low back pain. Publication research was performed on Medline, Cochrane, and PEDRO databases. Clinical trials were analyzed for internal validity, external validity, quality of statistical analysis, and quality of collection of adverse events. We present the best level of evidence. Bibliographic research identified 21 clinical trials and the coauthors added 5 references. The 26 trials represent 2695 patients. Some have good methodological quality and allow considering crenobalneotherapy as a potential treatment for low back pain, even if the role of mineral water remains uncertain. The methodological quality of therapeutic trials should be improved. These trials should be analyzed in the future guidelines on low back pain.

Macrophage immunomodulation through new polymers that recapitulate functional effects of itaconate as a power house of innate immunity.

Itaconate (ITA) is an emerging powerhouse of innate immunity with therapeutic potential that is limited in its ability to be administered in a soluble form. We developed a library of polyester materials that incorporate ITA into polymer backbones resulting in materials with inherent immunoregulatory behavior. Harnessing hydrolytic degradation release from polyester backbones, ITA polymers resulted in the mechanism specific immunoregulatory properties on macrophage polarization in vitro. In a functional assay, the polymer-released ITA inhibited bacterial growth on acetate. Translation to an in vivo model of biomaterial associated inflammation, intraperitoneal injection of ITA polymers demonstrated a rapid resolution of inflammation in comparison to a control polymer silicone, demonstrating the value of sustained biomimetic presentation of ITA.

Menoci: lightweight extensible web portal enhancing data management for biomedical research projects.

BACKGROUND: Biomedical research projects deal with data management requirements from multiple sources like funding agencies' guidelines, publisher policies, discipline best practices, and their own users' needs. We describe functional and quality requirements based on many years of experience implementing data management for the CRC 1002 and CRC 1190. A fully equipped data management software should improve documentation of experiments and materials, enable data storage and sharing according to the FAIR Guiding Principles while maximizing usability, information security, as well as software sustainability and reusability. RESULTS: We introduce the modular web portal software menoci for data collection, experiment documentation, data publication, sharing, and preservation in biomedical research projects. Menoci modules are based on the Drupal content management system which enables lightweight deployment and setup, and creates the possibility to combine research data management with a customisable project home page or collaboration platform. CONCLUSIONS: Management of research data and digital research artefacts is transforming from individual researcher or groups best practices towards project- or organisation-wide service infrastructures. To enable and support this structural transformation process, a vital ecosystem of open source software tools is needed. Menoci is a contribution to this ecosystem of research data management tools that is specifically designed to support biomedical research projects.

[Pain management in osteoporosis]. / Schmerztherapie bei Osteoporose.

Osteoporosis is a very common disease all over the world, in which a reduction in bone density can lead to an increased risk of fractures and a diminished physical height. Osteoporosis is also associated with acute and chronic pain, which especially occurs in the back and can significantly reduce the quality of life. To provide sufficient care for affected patients, it is essential to know the particularities of pain management in osteoporosis, such as pharmacological and nonpharmacological treatment options. This article gives a comprehensive review of pain management in osteoporosis and also explains the underlying pathomechanisms, risk factors, and diagnostic procedures.

[Pain management in osteoporosis]. / Schmerztherapie bei Osteoporose.

Osteoporosis is a very common disease all over the world, in which a reduction in bone density can lead to an increased risk of fractures and a diminished physical height. Osteoporosis is also associated with acute and chronic pain, which especially occurs in the back and can significantly reduce the quality of life. To provide sufficient care for affected patients, it is essential to know the particularities of pain management in osteoporosis, such as pharmacological and nonpharmacological treatment options. This article gives a comprehensive review of pain management in osteoporosis and also explains the underlying pathomechanisms, risk factors, and diagnostic procedures.

[Knee joint pain with signs of arthrosis]. / Kniegelenkschmerzen bei Arthrosezeichen.

Chronic pain in the knee joint is most commonly caused by osteoarthritis, especially in elderly patients but can be due to other causes, such as rheumatoid arthritis. The diagnostics include an exact patient medical history and a clinical examination, which often already provide clear indications of the cause of the knee pain. Subsequently, further diagnostics can then be considered, such as radiological procedures and laboratory diagnostics. The treatment is determined by the cause and the individual patient and aims to reduce pain and to preserve the mobility of the joint. Generally, therapy consists of pain management and physiotherapy as well as alternative therapeutic procedures, mostly in combination. Proximal tibial opening wedge osteotomy can be useful; however, partial or total knee arthroplasty should only be considered when conservative treatment options have been exhausted.

Mortality risk among workers with exposure to dioxins.

BACKGROUND: In several studies, dioxin exposure has been associated with increased risk from several causes of death. AIMS: To compare the mortality experience of workers exposed to dioxins during trichlorophenol (TCP) and pentachlorophenol (PCP) production to that of the general population and to examine mortality risk by estimated exposure levels. METHODS: A retrospective cohort study which followed up workers' vital status from 1940 to 2011, with serum surveys to support estimation of historical dioxin exposure levels. RESULTS: Among the 2192 study subjects, there were nine deaths in TCP workers from acute non-lymphatic leukaemia [standardized mortality ratio (SMR) = 2.88, 95% confidence interval (CI) 1.32-5.47], four mesothelioma deaths (SMR = 5.12, 95% CI 1.39-13.10) and four soft tissue sarcoma (STS) deaths (SMR = 3.08, 95% CI 0.84-7.87). In PCP workers, there were eight deaths from non-Hodgkin's lymphoma (SMR = 1.92, 95% CI 0.83-3.79), 150 from ischaemic heart disease (SMR = 1.20, 95% CI 1.01-7.89) and five from stomach ulcers (SMR = 3.38, 95% CI 1.10-7.89). There were no trends of increased mortality with increased dioxin exposure except for STS and 2,3,7,8-tetrachlorodibenzo-p-dioxin levels. This finding for STS should be interpreted with caution due to the small number of deaths and the uncertainty in diagnosis and nosology. CONCLUSIONS: While some causes of death were greater than expected, this study provides little evidence of increased risk when dioxin exposures are considered.

Effects of dialysis modality on blood loss, bleeding complications and transfusion requirements in critically ill patients with dialysis-dependent acute renal failure.

Blood loss and bleeding complications may often be observed in critically ill patients on renal replacement therapies (RRT). Here we investigate procedural (i.e. RRT-related) and non-procedural blood loss as well as transfusion requirements in regard to the chosen mode of dialysis (i.e. intermittent haemodialysis [IHD] versus continuous veno-venous haemofiltration [CVVH]). Two hundred and fifty-two patients (122 CVVH, 159 male; aged 61.5±13.9 years) with dialysis-dependent acute renal failure were analysed in a sub-analysis of the prospective randomised controlled clinical trial-CONVINT-comparing IHD and CVVH. Bleeding complications including severity of bleeding and RRT-related blood loss were assessed. We observed that 3.6% of patients died related to severe bleeding episodes (between group P=0.94). Major all-cause bleeding complications were observed in 23% IHD versus 26% of CVVH group patients (P=0.95). Under CVVH, the rate of RRT-related blood loss events (57.4% versus 30.4%, P=0.01) and mean total blood volume lost was increased (222.3±291.9 versus 112.5±222.7 ml per patient, P <0.001). Overall, transfusion rates did not differ between the study groups. In patients with sepsis, transfusion rates of all blood products were significantly higher when compared to cardiogenic shock (all P <0.01) or other conditions. In conclusion, procedural and non-procedural blood loss may often be observed in critically ill patients on RRT. In CVVH-treated patients, procedural blood loss was increased but overall transfusion rates remained unchanged. Our data show that IHD and CVVH may be regarded as equivalent approaches in critically ill patients with dialysis-dependent acute renal failure in this regard.

Intranasal administration of glial-derived neurotrophic factor (GDNF) rapidly and significantly increases whole-brain GDNF level in rats.

Previous studies have shown that glial cell line-derived neurotrophic factor (GDNF) exerts significant neuroprotective effects on substantia nigra (SN) neurons in the rat 6-hydroxydopamine (6-OHDA) model of Parkinson's disease (PD). In this study we used enzyme-linked immunosorbent assay (ELISA) to determine GDNF brain levels and distribution to target regions (i.e. striatum and SN) following intranasal administration of GDNF at different time points after administration. Brain levels increased significantly within 1h following a single 50-µg dose of GDNF in a liposomal formulation, returning to baseline by 24h. In a second study, different doses of GDNF (10-150 µg) in phosphate-buffered saline (PBS) were studied at the 1-h time point. Dose-dependent increases in brain GDNF levels were observed with apparent saturation of uptake at doses above 100 µg. Liposomes delivered 10-fold more GDNF to brain than PBS despite yielding similar neuroprotective efficacy in the 6-OHDA model, suggesting incomplete release of GDNF from liposomes in tissue. In a third study, autoradiography was performed on brain sections taken 1h after intranasal (125)I-labeled GDNF. Radioactivity was detected throughout the brain along the rostral-to-caudal axis, indicating that nasally administered GDNF can reach target areas. Collectively, these results demonstrate that intranasal administration of GDNF in liposomes or PBS achieves significant increases in GDNF in target brain areas, supporting use of intranasal administration as a non-invasive means of delivering GDNF to the brain to protect dopamine neurons and arrest disease progression in PD.

IVEU: IT-based collection and reporting of radiological examination parameters.

In Germany, each site using ionising radiation in human medicine is assigned to a competent medical authority (CMA) for quality assurance. Duties of these CMAs are, e.g. the inspection of medical aspects of the use of X-rays and nuclear medicine at the sites as well as technical quality assurance of X-ray devices. The CMAs themselves have to report the collected exposure values to the ministries and the Federal Office for Radiation Protection. The IVEU (IT-gestütztes Verfahren zur Erfassung von Untersuchungsparametern) Software Framework assists CMAs and radiological departments in collecting and analysing data provided in DICOM headers.

Evaluation of the effect of Lake Hévíz thermal mineral water in patients with osteoarthritis of the knee: a randomized, controlled, single-blind, follow-up study.

BACKGROUND: Osteoarthritis is the most frequent joint disease and is a leading cause of pain and locomotor disability in elderly people. The treatment of osteoarthritis includes non-pharmacological, pharmacological, and surgical therapies. Silver level evidence has been found concerning balneotherapy in osteoarthritis. AIM OF THE STUDY: The aim of this study was to evaluate how Lake Hévíz thermal mineral water therapy influences pain, knee function, and quality of life in patients with knee osteoarthritis, compared to the control group. STUDY DESIGN: randomized, controlled, single-blind, follow-up study. SETTING: Spa Hévíz and St. Andrew Hospital for Rheumatic Diseases POPULATION: This study included 77 outpatients between 45 and 75 years of age with mild to moderate osteoarthritis of the knee meeting the American College of Rheumatology classification criteria. METHODS: Patients were randomized into two groups. In group I (n = 38), subjects bathed in Lake Hévíz and in group II (N.=39), patients were treated in a pool full of tap water. Water temperature was 34 °C for both groups. Participants underwent 30-minute therapy sessions, five times a week for three weeks. Outcome measures were pain visual analogue scale scores, active flexion degree, knee circumference, stair-climb time, Western Ontario and McMaster Universities osteoarthritis index (WOMAC), and EuroQoL Group 5-Dimension Self-Report Questionnaire score (EQ-5D). Study parameters were recorded at baseline, immediately after treatment, and after 15 weeks. RESULTS: Comparison of the two groups revealed a statistically significant difference in pain visual analogue scale scores (P<0.01), active flexion degree (P<0.01), physical function components of WOMAC (P<0.05), and EQ-5D scores (P<0.05) even after 15 weeks. CONCLUSIONS: Balneotherapy improved pain, function as well as the quality of life in patients with knee osteoarthritis. CLINICAL REHABILITATION IMPACT: Balneotherapy is a potentially useful treatment modality for patients with knee osteoarthritis.

Evidence-based hydro- and balneotherapy in Hungary--a systematic review and meta-analysis.

Balneotherapy is appreciated as a traditional treatment modality in medicine. Hungary is rich in thermal mineral waters. Balneotherapy has been in extensive use for centuries and its effects have been studied in detail. Here, we present a systematic review and meta-analysis of clinical trials conducted with Hungarian thermal mineral waters, the findings of which have been published by Hungarian authors in English. The 122 studies identified in different databases include 18 clinical trials. Five of these evaluated the effect of hydro- and balneotherapy on chronic low back pain, four on osteoarthritis of the knee, and two on osteoarthritis of the hand. One of the remaining seven trials evaluated balneotherapy in chronic inflammatory pelvic diseases, while six studies explored its effect on various laboratory parameters. Out of the 18 studies, 9 met the predefined criteria for meta-analysis. The results confirmed the beneficial effect of balneotherapy on pain with weight bearing and at rest in patients with degenerative joint and spinal diseases. A similar effect has been found in chronic pelvic inflammatory disease. The review also revealed that balneotherapy has some beneficial effects on antioxidant status, and on metabolic and inflammatory parameters. Based on the results, we conclude that balneotherapy with Hungarian thermal-mineral waters is an effective remedy for lower back pain, as well as for knee and hand osteoarthritis.

c-Myb and its target Bmi1 are required for p190BCR/ABL leukemogenesis in mouse and human cells.

Expression of c-Myb is required for normal hematopoiesis and for proliferation of myeloid leukemia blasts and a subset of T-cell leukemia, but its role in B-cell leukemogenesis is unknown. We tested the role of c-Myb in p190(BCR/ABL)-dependent B-cell leukemia in mice transplanted with p190(BCR/ABL)-transduced marrow cells with a c-Myb allele (Myb(f/d)) and in double transgenic p190(BCR/ABL)/Myb(w/d) mice. In both models, loss of a c-Myb allele caused a less aggressive B-cell leukemia. In p190(BCR/ABL)-expressing human B-cell leukemia lines, knockdown of c-Myb expression suppressed proliferation and colony formation. Compared with c-Myb(w/f) cells, expression of Bmi1, a regulator of stem cell proliferation and maintenance, was decreased in pre-B cells from Myb(w/d) p190(BCR/ABL) transgenic mice. Ectopic expression of a mutant c-Myb or Bmi1 enhanced the proliferation and colony formation of Myb(w/d) p190(BCR/ABL) B-cells; by contrast, Bmi1 downregulation inhibited colony formation of p190(BCR/ABL)-expressing murine B cells and human B-cell leukemia lines. Moreover, c-Myb interacted with a segment of the human Bmi1 promoter and enhanced its activity. In blasts from 19 Ph(1) adult acute lymphoblastic leukemia patients, levels of c-Myb and Bmi1 showed a positive correlation. Together, these findings support the existence of a c-Myb-Bmi1 transcription-regulatory pathway required for p190(BCR/ABL) leukemogenesis.

Effects of brain-derived neurotrophic factor on dopaminergic function and motor behavior during aging.

Brain-derived neurotrophic factor (BDNF) is critical in synaptic plasticity and in the survival and function of midbrain dopamine neurons. In this study, we assessed the effects of a partial genetic deletion of BDNF on motor function and dopamine (DA) neurotransmitter measures by comparing Bdnf(+/-) with wildtype mice (WT) at different ages. Bdnf(+/-) and WT mice had similar body weights until 12 months of age; however, at 21 months, Bdnf(+/-) mice were significantly heavier than WT mice. Horizontal and vertical motor activity was reduced for Bdnf(+/-) compared to WT mice, but was not influenced by age. Performance on an accelerating rotarod declined with age for both genotypes and was exacerbated for Bdnf(+/-) mice. Body weight did not correlate with any of the three behavioral measures studied. Dopamine neurotransmitter markers indicated no genotypic difference in striatal tyrosine hydroxylase, DA transporter (DAT) or vesicular monoamine transporter 2 (VMAT2) immunoreactivity at any age. However, DA transport via DAT (starting at 12 months) and VMAT2 (starting at 3 months) as well as KCl-stimulated DA release were reduced in Bdnf(+/-) mice and declined with age suggesting an increasingly important role for BDNF in the release and uptake of DA with the aging process. These findings suggest that a BDNF expression deficit becomes more critical to dopaminergic dynamics and related behavioral activities with increasing age.

PD and loss of peritoneal function.

During long-term treatment with peritoneal dialysis both peritoneal membrane structure and function undergo significant changes that not only correlate with the time under treatment, but also with the frequency and severity of infections. In addition, peritoneal dialysis fluid bio-incompatibility may constitute a hazard for the longevity of the peritoneum as the dialysis membrane. In particular, the presence of glucose degradation products may lead to impaired peritoneal cell function as well as to increased protein glycation and peritoneal AGE deposition. Results from recent prospective randomised studies suggest that treatment with new GDP-depleted PD fluids may lead to a significant improvement of clinical outcomes in PD patients.

Correlation between HSP-72 expression and IL-8 secretion in human mesothelial cells.

BACKGROUND: Cytotoxicity of peritoneal dialysis fluid (PDF) and peritoneal inflammation are currently regarded as the two major culprits for chronic mesothelial injury and peritoneal membrane failure. In this study, we correlated induction of HSP-72, as a marker of the cellular stress response, to secretion of IL-8, as a marker for pro-inflammatory cytokines, in mesothelial cells upon sublethal PDF exposure. METHODS: Primary omental cell cultures of human mesothelial cells were subjected to sublethal PDF exposure times (CAPD2, Fresenius, Germany). At the end of a 24 hour recovery period, induction of HSP-72 in the cell homogenate and IL-8 secretion in the supernatant was assessed by immunodensitometry and ELISA, respectively. RESULTS: PDF exposure times from 15 min to 60 min resulted in progressively increased HSP-72 expression levels (267 vs 320 vs 419% of controls, p<0.05 vs controls) as well as increased IL-8 secretion (323 vs 528 vs 549% of controls, p<0.05 vs controls) with full cell viability (MTT unchanged to control). HSP-72 expression was statistically significantly correlated with IL-8 secretion. CONCLUSIONS: The significant correlation between HSP-72 expression and IL-8 secretion suggests that the regulation of pro-inflammatory pathways in mesothelial cells exposed to PDF may represent an integral part of their stress response. Future studies to investigate the cellular regulatory mechanism involved are warranted.

Cancer incidence among semiconductor and electronic storage device workers.

AIMS: To evaluate cancer incidence among workers at two facilities in the USA that made semiconductors and electronic storage devices. METHODS: 89 054 men and women employed by International Business Machines (IBM) were included in the study. We compared employees' incidence rates with general population rates and examined incidence patterns by facility, duration of employment, time since first employment, manufacturing era, potential for exposure to workplace environments other than offices and work activity. RESULTS: For employees at the semiconductor manufacturing facility, the standardised incidence ratio (SIR) for all cancers combined was 81 (1541 observed cases, 95% confidence interval (CI) 77 to 85) and for those at the storage device manufacturing facility the SIR was 87 (1319 observed cases, 95% CI 82 to 92). The subgroups of employees with > or =15 years since hiring and > or =5 years worked had 6-16% fewer total incidents than expected. SIRs were increased for several cancers in certain employee subgroups, but analyses of incidence patterns by potential exposure and by years spent and time since starting in specific work activities did not clearly indicate that the excesses were due to occupational exposure. CONCLUSIONS: This study did not provide strong or consistent evidence of causal associations with employment factors. Data on employees with long potential induction time and many years worked were limited. Further follow-up will allow a more informative analysis of cancer incidence that might be plausibly related to workplace exposures in the cohort.

Comparison of icodextrin- and glucose-based peritoneal dialysis fluids in their acute and chronic effects on human peritoneal mesothelial cells.

BACKGROUND: Icodextrin-based peritoneal dialysis fluids (PDFs) display several features that may potentially improve their biocompatibility compared to conventional glucose-containing solutions. So far, however, the studies assessing the biocompatibility profile of icodextrin toward human peritoneal mesothelial cells (HPMC) has produced mixed results. The present study was performed to examine the acute and chronic impact of icodextrin on HPMC in vitro in comparison with standard glucose-based PDF. METHODS: Omentum-derived HPMC were either acutely pre-exposed to or incubated chronically (for up to 10 days) in the presence of icodextrin-PDF. Parallel cultures were treated with conventional PDFs containing either 1.5% or 4.25% glucose. All fluids were tested at neutral pH. HPMC were assessed for viability, proliferation, IL-6 secretion and generation of reactive oxygen species (ROS). RESULTS: Incubation in the presence of icodextrin-PDF significantly reduced HPMC proliferation in a manner similar to that of 1.5% glucose-PDF. In addition, exposure to icodextrin-PDF impaired viability and IL-6 release from HPMC. This effect occurred both after the short pre-treatment with neat icodextrin-PDF for 1-4 hours and after prolonged incubation (up to 10 days) in media supplemented with icodextrin-PDF (1:1). The dysfunction of icodextrin-treated HPMC was of the magnitude that was between the effects exerted by 1.5%- and 4.25%-glucose PDF. Furthermore, exposure of HPMC to icodextrin-PDF induced a dose-dependent increase in ROS generation which was comparable to that produced by 1.5%-glucose PDF. CONCLUSION: Exposure to icodextrin-PDF may impair viability and function of HPMC. The detrimental effects of icodextrin-PDF are at least as serious as those produced by conventional heat-sterilized low glucose-based PDF.