Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity

Multiple sclerosis (MS) disease risk is associated with reduced sun-exposure. This study assessed the relationship between measures of sun exposure (vitamin D [vitD], latitude) and MS severity in the setting of two multicenter cohort studies (n(NationMS) = 946, n(BIONAT) = 990). Additionally, effect-modification by medication and photosensitivity-associated MC1R variants was assessed. High serum vitD was associated with a reduced MS severity score (MSSS), reduced risk for relapses, and lower disability accumulation over time. Low latitude was associated with higher vitD, lower MSSS, fewer gadolinium-enhancing lesions, and lower disability accumulation. The association of latitude with disability was lacking in IFN-β-treated patients. In carriers of MC1R:rs1805008(T), who reported increased sensitivity toward sunlight, lower latitude was associated with higher MRI activity, whereas for noncarriers there was less MRI activity at lower latitudes. In a further exploratory approach, the effect of ultraviolet (UV)-phototherapy on the transcriptome of immune cells of MS patients was assessed using samples from an earlier study. Phototherapy induced a vitD and type I IFN signature that was most apparent in monocytes but that could also be detected in B and T cells. In summary, our study suggests beneficial effects of sun exposure on established MS, as demonstrated by a correlative network between the three factors: Latitude, vitD, and disease severity. However, sun exposure might be detrimental for photosensitive patients. Furthermore, a direct induction of type I IFNs through sun exposure could be another mechanism of UV-mediated immune-modulation in MS

Modularization of Domain-Specific Languages for Extensible Component-Based Robotic Systems

Wigand DL, Nordmann A, Goerlich M, Wrede S. Modularization of Domain-Specific Languages for Extensible Component-Based Robotic Systems. In: Proceedings of the First IEEE International Conference on Robotic Computing. 2017

The nature of respiratory muscle weakness in patients with late-onset Pompe disease

Late-onset Pompe disease (LOPD) causes myopathy of skeletal and respiratory muscles, and phrenic nerve pathology putatively contributes to diaphragm weakness. The aim of this study was to investigate neural contributions to diaphragm dysfunction, usefulness of diaphragm ultrasound, and involvement of expiratory abdominal muscles in LOPD. Thirteen patients with LOPD (7 male, 51 +/- 17 years) and 13 age- and gender-matched controls underwent respiratory muscle strength testing, ultrasound evaluation of diaphragm excursion and thickness, cortical and cervical magnetic stimulation (MS) of the diaphragm with simultaneous recording of surface electromyogram and twitch transdiaphragmatic pressure (twPdi; n = 6), and MS of the abdominal muscles with recording of twitch gastric pressure (twPgas; n = 6). The following parameters were significantly reduced in LOPD patients versus controls: forced vital capacity (p<0.01), maximum inspiratory and expiratory pressure (both p<0.001), diaphragm excursion velocity (p<0.05), diaphragm thickening ratio (1.8 +/- 0.4 vs. 2.6 +/- 0.6, p<0.01), twPdi following cervical MS (12.0 +/- 6.2 vs. 19.4 +/- 4.8 cmH(2)O, p<0.05), and twPgas following abdominal muscle stimulation (8.8 +/- 8.1 vs. 34.6 +/- 17.1 cmH(2)O, p<0.01). Diaphragm motor evoked potentials and compound muscle action potentials showed no between-group differences. In conclusion, phrenic nerve involvement in LOPD could not be electrophysiologically confirmed. Ultrasound supports assessment of diaphragm function. Abdominal expiratory muscles are functionally involved in LOPD. (C) 2019 Elsevier B.V. All rights reserved

Respiratory muscle weakness in facioscapulohumeral muscular dystrophy

Introduction The purpose of this study was to comprehensively evaluate respiratory muscle function in adults with facioscapulohumeral muscular dystrophy (FSHD). Methods Fourteen patients with FSHD (9 men, 53 +/- 16 years of age) and 14 matched controls underwent spirometry, diaphragm ultrasound, and measurement of twitch gastric and transdiaphragmatic pressures (twPgas and twPdi; n = 10) after magnetic stimulation of the lower thoracic nerve roots and the phrenic nerves. The latter was combined with recording of diaphragm compound muscle action potentials (CMAPs; n = 14). Results The following parameters were significantly lower in patients vs controls: forced vital capacity (FVC); maximum inspiratory and expiratory pressure; peak cough flow; diaphragm excursion amplitude; and thickening ratio on ultrasound, twPdi (11 +/- 5 vs 20 +/- 6 cmH(2)O) and twPgas (7 +/- 3 vs 25 +/- 20 cmH(2)O). Diaphragm CMAP showed no group differences. FVC correlated inversely with the clinical severity scale score (r = -0.63, P = .02). Discussion In FSHD, respiratory muscle weakness involves both the diaphragm and the expiratory abdominal muscles

Characteristics of respiratory muscle involvement in myotonic dystrophy type 1

The pathophysiology of respiratory muscle weakness in myotonic dystrophy type 1 (DM1) remains incompletely understood. 21 adult patients with DM1 (11 men, 42 +/- 13 years) and 21 healthy matched controls underwent spirometry, manometry, and diaphragm ultrasound. In addition, surface electromyography of the diaphragm and the obliquus abdominis muscle was performed following cortical and posterior cervical magnetic stimulation (CMS) of the phrenic nerves or magnetic stimulation of the lower thoracic nerve roots. Magnetic stimulation was combined with invasive recording of the twitch transdiaphragmatic and gastric pressure (twPdi and twPgas) in 10 subjects per group. The following parameters were reduced in DM1 patients compared to control subjects: maximum inspiratory pressure (MIP; 40.3 +/- 19.2 vs. 95.8 +/- 28.5 cmH(2)O, p < 0.01), diaphragm thickening ratio (DTR; 2.0 +/- 0.4 vs. 2.7 +/- 0.6, p < 0.01), twPdi following CMS (10.8 +/- 8.3 vs. 21.4 +/- 10.1 cmH2O, p = 0.03), and amplitude of diaphragm compound muscle action potentials (0.10 +/- 0.25 vs. 0.46 +/- 0.35 mV; p = 0.04). MIP and DTR were significantly correlated with the muscular impairment rating scale (MIRS) score. Maximum expiratory pressure (MEP) was reduced in DM1 patients compared to controls (41.3 +/- 13.4 vs. 133.8 +/- 28.0 cmH2O, p < 0.01) and showed negative correlation with the MIRS score. Pgas following a maximum cough was markedly lower in patients than in controls (71.9 +/- 43.2 vs. 102.4 +/- 35.5 cmH(2)O) but without statistical significance (p = 0.06). In DM1, respiratory muscle weakness relates to clinical disease severity and involves inspiratory and probably expiratory muscle strength. Axonal phrenic nerve pathology may contribute to diaphragm dysfunction. (C) 2019 Elsevier B.V. All rights reserved

Tumor infiltrating T cells influence prognosis in stage I-III non-small cell lung cancer

Background: T cell infiltration in non-small cell lung cancer (NSCLC) is essential for the immunological response to malignant tissue, especially in the era of immune-checkpoint inhibition. To investigate the prognostic impact of CD4(+) T helper cells (T-h), CD8(+) cytotoxic (T-c) and FOXP3(+) regulatory T (T-reg) cells in NSCLC, we performed this analysis. Methods: By counterstaining of CD4, CD8 and FOXP3 we used immunohistochemistry on tissue microarrays (TMA) to evaluate peritumoral T-h cells, T(reg )cells and T-c cells in n=294 NSCLC patients with pTNM stage I-III disease. Results: Strong CD4(+) infiltration was associated with higher tumor stages and lymphonodal spread. However, strong CD4(+) infiltration yielded improved overall survival (OS) (P=0.014) in adenocarcinoma (ADC) and large cell carcinoma (LCC) but not in squamous cell carcinoma (SCC). A CD4/CD8 ratio 0.05). Here, prognostic effects were prominent in PD-L1 positive SCC (P=0.023) but not in PD-L1 negative SCC (P=0.236). Conclusions: High proportion of CD8(+) T-c cells correlated with improved prognostic outcome in stage I-III NSCLC. T-h cells and T-reg cells have implications on outcome with respect to tumor histology and biology

Respiratory Muscle Function Tests and Diaphragm Ultrasound Predict Nocturnal Hypoventilation in Slowly Progressive Myopathies

Introduction: In slowly progressive myopathies, diaphragm weakness early manifests through sleep-related hypoventilation as reflected by nocturnal hypercapnia. This study investigated whether daytime tests of respiratory muscle function and diaphragm ultrasound predict hypercapnia during sleep. Methods: Twenty-seven patients with genetic myopathies (myotonic dystrophy type 1 and 2, late-onset Pompe disease, facioscapulohumeral dystrophy; 48 +/- 11 years) underwent overnight transcutaneous capnometry, spirometry, measurement of mouth occlusion pressures, and diaphragm ultrasound. Results: Sixteen out of 27 patients showed nocturnal hypercapnia (peak p(tc)CO(2) >= 50 mmHg for >= 30 min or increase in p(tc)CO(2) by 10 mmHg or more from the baseline value). In these patients, forced vital capacity (FVC; % predicted) and maximum inspiratory pressure (MIP; % of lower limit or normal or LLN) were significantly reduced compared to normocapnic individuals. Nocturnal hypercapnia was predicted by reduction in FVC of Conclusion: In slowly progressive myopathies, nocturnal hypercapnia is predicted by FVC 8.0 cm/s on diaphragm ultrasound.</p