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Functional electrical stimulation (FES) can support functional restoration of a paretic limb post-stroke. Hebbian plasticity depends on temporally coinciding pre- and post-synaptic activity. A tight temporal relationship between motor cortical (MC) activity associated with attempted movement and FES-generated visuo-proprioceptive feedback is hypothesized to enhance motor recovery. Using a brain–computer interface (BCI) to classify MC spectral power in electroencephalographic (EEG) signals to trigger FES-delivery with detection of movement attempts improved motor outcomes in chronic stroke patients. We hypothesized that heightened neural plasticity earlier post-stroke would further enhance corticomuscular functional connectivity and motor recovery. We compared subcortical non-dominant hemisphere stroke patients in BCI-FES and Random-FES (FES temporally independent of MC movement attempt detection) groups. The primary outcome measure was the Fugl-Meyer Assessment, Upper Extremity (FMA-UE). We recorded high-density EEG and transcranial magnetic stimulation-induced motor evoked potentials before and after treatment. The BCI group showed greater: FMA-UE improvement; motor evoked potential amplitude; beta oscillatory power and long-range temporal correlation reduction over contralateral MC; and corticomuscular coherence with contralateral MC. These changes are consistent with enhanced post-stroke motor improvement when movement is synchronized with MC activity reflecting attempted movement. [ABSTRACT FROM AUTHOR]

In recent years, there have been intense international discussions about the definition and terminology of language disorders in childhood, such as those sparked by the publications of the CATALISE consortium. To address this ongoing debate, a Delphi study was conducted in German-speaking countries. This study consisted of three survey waves and involved over 400 experts from relevant disciplines. As a result, a far-reaching consensus was achieved on essential definition criteria and terminology, presented in 23 statements. The German term 'Sprachentwicklungsstörung' was endorsed to refer to children with significant deviations from typical language development that can negatively impact social interactions, educational progress, and/or social participation and do not occur together with a potentially contributing impairment. A significant deviation from typical language development was defined as a child's scores in standardized test procedures being ≥ 1.5 SD below the mean for children of the same age. The results of this Delphi study provide a proposal for a uniform use of terminology for language disorders in childhood in German-speaking countries. [ABSTRACT FROM AUTHOR]

Pain currently plays a subordinate role in the clinical care of patients with ALS. We aim to examine epidemiological and clinical characteristics of pain as well as its impact throughout the disease course. During a longitudinal follow-up at three time points, 151 ALS patients from three German outpatient clinics completed the Brief Pain Inventory, ALS-Functional Rating Scale-Extension and ALS Depression Inventory. Analysis of variance and covariance with repeated measures were performed. Pain was prevalent in 56% of the 151 patients at baseline and in 70% of the remaining 40 patients at the third survey. Of the 28 patients with pain who participated in all three surveys, about two thirds suffered from an average pain intensity corresponding to at least moderate pain on the numerical rating scale (NRS ≥ 4). Patients reported different pain qualities and localized the pain most frequently in the extremities, back and neck. Pain moderately impaired the functions of daily living. Pain intensity, pain quality and pain-related impairment did not significantly change over time. One third of the patients suffered from clinically relevant depressive symptoms. However, there was no conclusive evidence of a link between pain intensity and depressive symptoms. Pain is frequent and constitutes an additional strain on ALS patients who have to endure a rapidly progressive and severely debilitating disease. This study contributes to better understanding of the characteristics of pain and its impact on ALS patients throughout the disease course and may thus help to more effectively address this symptom. [ABSTRACT FROM AUTHOR]

Purpose: Cumyl-PEGACLONE was the first synthetic cannabinoid (SC) with a γ-carbolinone core structure detected in forensic casework and, since then, it has dominated the German SC-market. Here the first four cases of death involving its fluorinated analog, 5F-Cumyl-PEGACLONE, a recently emerged γ-carbolinone derived SC, are reported. Methods: Complete postmortem examinations were performed. Postmortem samples were screened by immunoassay, gas chromatography mass spectrometry (GC–MS) or liquid chromatography tandem mass spectrometry. For quantification of SCs, the standard addition method was employed. Herbal blends were analyzed by GC–MS. In each case of death, the Toxicological Significance Score (TSS) was assigned to the compound. Results: 5F-Cumyl-PEGACLONE was identified at concentrations ranging 0.09–0.45 ng/mL in postmortem femoral blood. In case 1, signs of hypothermia and kidney bleedings were noted. Despite a possible tolerance due to long term SC use, a TSS of 3 was assigned. In case 2, an acute heroin intoxication occurred and a contributory role (TSS = 1) of 5F-Cumyl-PEGACLONE was suggested. In case 3, a prisoner was found dead. GC–MS analysis of herbal blends, retrieved in his cell together with paraphernalia, confirmed the presence of 5F-Cumyl-PEGACLONE and a causative role was deemed probable (TSS = 2). In case 4, the aspiration of gastric content due to a SC-induced coma was observed (TSS = 3). Conclusions: 5F-Cumyl-PEGACLONE is an emerging and extremely potent SC which raises serious public health concerns. A comprehensive analysis of circumstantial, clinical, and postmortem findings, as well as an in-depth toxicological analysis is necessary for a valid interpretation and for the assessment of the toxicological significance. [ABSTRACT FROM AUTHOR]

The upper cervical spinal cord is measured in a large longitudinal amyotrophic lateral sclerosis (ALS) cohort to evaluate its role as a biomarker. Specifically, the cervical spinal cord´s cross-sectional area (CSA) in plane of the segments C1–C3 was measured semi-automatically with T1-weighted 3T MRI sequences in 158 ALS patients and 86 controls. Six-month longitudinal follow-up MRI scans were analyzed in 103 patients. Compared to controls, in ALS there was a significant mean spinal cord atrophy (63.8 mm² vs. 60.8 mm², p = 0.001) which showed a trend towards worsening over time (mean spinal cord CSA decrease from 61.4 mm² to 60.6 mm² after 6 months, p = 0.06). Findings were most pronounced in the caudal segments of the upper cervical spinal cord and in limb-onset ALS. Baseline CSA was related to the revised ALS functional rating scale, disease duration, precentral gyrus thickness and total brain gray matter volume. In conclusion, spinal cord atrophy as assessed in brain MRIs in ALS patients mirrors the extent of overall neurodegeneration and parallels disease severity. [ABSTRACT FROM AUTHOR]

Motor recovery following stroke is believed to necessitate alteration in functional connectivity between cortex and muscle. Cortico-muscular coherence has been proposed as a potential biomarker for post-stroke motor deficits, enabling a quantification of recovery, as well as potentially indicating the regions of cortex involved in recovery of function. We recorded simultaneous EEG and EMG during wrist extension from healthy participants and patients following ischaemic stroke, evaluating function at three time points post-stroke. EEG–EMG coherence increased over time, as wrist mobility recovered clinically, and by the final evaluation, coherence was higher in the patient group than in the healthy controls. Moreover, the cortical distribution differed between the groups, with coherence involving larger and more bilaterally scattered areas of cortex in the patients than in the healthy participants. The findings suggest that EEG–EMG coherence has the potential to serve as a biomarker for motor recovery and to provide information about the cortical regions that should be targeted in rehabilitation therapies based on real-time EEG. [ABSTRACT FROM AUTHOR]

Purpose: Semantic learning under 2 co-speech gesture conditions was investigated in children with specific language impairment (SLI) and typically developing (TD) children. Learning was analyzed between conditions. Method: Twenty children with SLI (aged 4 years), 20 TD children matched for age, and 20 TD children matched for language scores were taught rare nouns and verbs. Children heard the target words while seeing either iconic gestures illustrating a property of the referent or a control gesture focusing children's attention on the word. Following training, children were asked to define the words' meaning. Responses were coded for semantic information provided on each word. Results: Performance of the SLI and age-matched groups proved superior to that of the language-matched group. Overall, children defined more words taught with iconic gestures than words taught with attention-getting gestures. However, only children with SLI, but not TD children, provided more semantic information on each word taught with iconic gestures. Performance did not differ in terms of word class. Conclusions: Results suggest that iconic co-speech gestures help both children with and without SLI learn new words but, in particular, assist children with SLI understand and reflect the words' meaning. [ABSTRACT FROM AUTHOR]

Research has shown that observing iconic gestures helps typically developing children (TD) and children with specific language impairment (SLI) learn new words. So far, studies mostly compared word learning with and without gestures. The present study investigated word learning under two gesture conditions in children with and without language impairment. Twenty children with SLI (age four), twenty age-matched TD children, and twenty language-matched TD children were taught words that were presented with either iconic or non-iconic gestures. Results showed that children of all groups benefited more successfully from observing iconic gestures for word learning. The iconic gesture advantage was similar across groups. Thus, observing iconic gestures prompts richer encoding and makes word learning more efficient in TD and language impaired children. [ABSTRACT FROM PUBLISHER]

Background: A risk-targeted prevention strategy may efficiently utilize limited resources available for prevention of overweight and obesity. Likewise, more efficient intervention trials could be designed if selection of subjects was based on risk. The aim of the study was to develop a risk score predicting substantial weight gain among German adults. Methods: We developed the risk score using information on 15 socio-demographic, dietary and lifestyle factors from 32 204 participants of five population-based German cohort studies. Substantial weight gain was defined as gaining-10% of weight between baseline and follow-up (>6 years apart). The cases were censored according to the theoretical point in time when the threshold of 10% baseline-based weight gain was crossed assuming linearity of weight gain. Beta coefficients derived from proportional hazards regression were used as weights to compute the risk score as a linear combination of the predictors. Cross-validation was used to evaluate the score's discriminatory accuracy. Results: The cross-validated c index (95% CI) was 0.71 (0.67-0.75). A cutoff value of ≥475 score points yielded a sensitivity of 71% and a specificity of 63%. The corresponding positive and negative predictive values were 10.4% and 97.6%, respectively. Conclusions: The proposed risk score may support healthcare providers in decision making and referral and facilitate an efficient selection of subjects into intervention trials. [ABSTRACT FROM AUTHOR]

Objective: To examine the interaction between waist circumference (WC) and serum 25-hydroxyvitamin D (25(OH)D) level in their associations with serum lipids.Design: Cross-sectional study. The associations of serum 25(OH)D with total cholesterol, HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), LDL-C:HDL-C and TAG were examined using multiple linear regression. Effect modification by WC was assessed through cross-product interaction terms between 25(OH)D and WC categories (abdominal overweight, 80-<88 cm in females/94-<102 cm in males; abdominal obesity, ≥88 cm in females/≥102 cm in males).Setting: The US National Health and Nutrition Examination Survey waves 2001-2006.Subjects: Non-pregnant fasting participants (n 4342) aged ≥20 years.Results: Lower 25(OH)D levels were significantly associated with lower HDL-C levels as well as with higher LDL-C:HDL-C and TAG levels in abdominally obese participants, but not in abdominally overweight or normal-waist participants. In contrast, lower 25(OH)D levels were associated with lower levels of total cholesterol and LDL-C in abdominally overweight and normal-waist participants only, but this association was only partly significant. However, a significant difference in the association between 25(OH)D and the lipids according to WC category was found only for LDL-C:HDL-C (P for interaction=0·02).Conclusions: Our results from this large, cross-sectional sample suggest that the association between lower 25(OH)D levels and an unfavourable lipid profile is stronger in individuals with abdominal obesity than in those with abdominal overweight or a normal WC. [ABSTRACT FROM AUTHOR]

ObjectiveAs ageing is associated with changes in body composition, BMI may not be the appropriate obesity measure for older adults. To date, little is known about associations between obesity measures and health-related quality of life (HRQoL). Thus, we aimed to compare different obesity measures in their association with HRQoL and self-rated physical constitution (SRPC) in older adults.DesignSeven obesity measures (BMI, waist circumference (WC), waist-to-hip ratio, waist-to-height ratio, fat mass percentage based on bioelectrical impedance analysis, hypertriglyceridaemic waist (HTGW) and sarcopenic obesity) were assessed at baseline in 2009. HRQoL, using the EQ-5D questionnaire, and SRPC, using one single question, were collected at baseline and at the 3-year follow-up in 2012. Linear and logistic regression analyses were used to examine the associations between the obesity measures and both outcomes. Model comparisons were conducted by area under the receiver-operating characteristic curve, R2, Akaike and Schwarz Bayesian information criteria.SettingKORA-Age study in Southern Germany (2009–2012).SubjectsOlder adults (n 883; aged ≥65 years).ResultsNearly all obesity measures were significantly inversely associated with both outcomes in cross-sectional analyses. Concerning HRQoL, the WC model explained most of the variance and had the best model adaption, followed by the BMI model. Regarding SRPC, the HTGW and BMI models were best as rated by model quality criteria, followed closely by the WC model. Longitudinal analyses showed no significant associations.ConclusionsThese results suggest that, with regard to HRQoL/SRPC, simple anthropometric measures are sufficient to determine obesity in older adults in medical practice. [ABSTRACT FROM AUTHOR]

Objective: As ageing is associated with changes in body composition, BMI may not be the appropriate obesity measure for older adults. To date, little is known about associations between obesity measures and health-related quality of life (HRQoL). Thus, we aimed to compare different obesity measures in their association with HRQoL and self-rated physical constitution (SRPC) in older adults.Design: Seven obesity measures (BMI, waist circumference (WC), waist-to-hip ratio, waist-to-height ratio, fat mass percentage based on bioelectrical impedance analysis, hypertriglyceridaemic waist (HTGW) and sarcopenic obesity) were assessed at baseline in 2009. HRQoL, using the EQ-5D questionnaire, and SRPC, using one single question, were collected at baseline and at the 3-year follow-up in 2012. Linear and logistic regression analyses were used to examine the associations between the obesity measures and both outcomes. Model comparisons were conducted by area under the receiver-operating characteristic curve, R 2, Akaike and Schwarz Bayesian information criteria.Setting: KORA-Age study in Southern Germany (2009-2012).Subjects: Older adults (n 883; aged ≥65 years).Results: Nearly all obesity measures were significantly inversely associated with both outcomes in cross-sectional analyses. Concerning HRQoL, the WC model explained most of the variance and had the best model adaption, followed by the BMI model. Regarding SRPC, the HTGW and BMI models were best as rated by model quality criteria, followed closely by the WC model. Longitudinal analyses showed no significant associations.Conclusions: These results suggest that, with regard to HRQoL/SRPC, simple anthropometric measures are sufficient to determine obesity in older adults in medical practice. [ABSTRACT FROM AUTHOR]

Aim: This study aims to quantify longitudinal changes in waist circumference (WC) among adults aged 45-64 years in Germany. Methods: Data of 15,444 men and 17,207 women from one nationwide and six regional prospective German cohort studies were analyzed. The sex-specific mean change in WC per year of follow-up was assessed for each study separately. Findings from the cohort-by-cohort analysis were combined by applying meta-analytic methods. Progression to central obesity (WC ≥ 102 cm in men and ≥ 88 cm in women) within a standardized period of 10 years was described for each study. Results: The estimated mean change in WC per year of follow-up for all cohorts combined was 0.53 (95% confidence interval 0.29-0.76) cm/year for men and 0.63 (0.48-0.77) cm/year for women, but varied between the included studies. Within 10 years, about 20% of individuals with low WC (<94 cm in men; <80 cm in women) and about 50% of individuals with intermediate WC (94-102 cm in men; 80-88 cm in women) progressed to central obesity. Conclusion: The increase in mean WC with aging along with a profound increase of central adiposity is obviously and may have several adverse health effects. Obesity prevention programs should also focus on abdominal obesity. [ABSTRACT FROM AUTHOR]

Background: Numerous observational studies have observed associations between vitamin D deficiency and cardiometabolic diseases, but these findings might be confounded by obesity. A characterization of the metabolic profile associated with serum 25-hydroxyvitamin D [25(OH)D] levels, in general and stratified by abdominal obesity, may help to untangle the relationship between vitamin D, obesity and cardiometabolic health.Methods: Serum metabolomics measurements were obtained from a nuclear magnetic resonance spectroscopy (NMR)- and a mass spectrometry (MS)-based platform. The discovery was conducted in 1726 participants of the population-based KORA-F4 study, in which the associations of the concentrations of 415 metabolites with 25(OH)D levels were assessed in linear models. The results were replicated in 6759 participants (NMR) and 609 (MS) participants, respectively, of the population-based FINRISK 1997 study.Results: Mean [standard deviation (SD)] 25(OH)D levels were 15.2 (7.5) ng/ml in KORA F4 and 13.8 (5.9) ng/ml in FINRISK 1997; 37 metabolites were associated with 25(OH)D in KORA F4 at P < 0.05/415. Of these, 30 associations were replicated in FINRISK 1997 at P < 0.05/37. Among these were constituents of (very) large very-low-density lipoprotein and small low-density lipoprotein subclasses and related measures like serum triglycerides as well as fatty acids and measures reflecting the degree of fatty acid saturation. The observed associations were independent of waist circumference and generally similar in abdominally obese and non-obese participants.Conclusions: Independently of abdominal obesity, higher 25(OH)D levels were associated with a metabolite profile characterized by lower concentrations of atherogenic lipids and a higher degree of fatty acid polyunsaturation. These results indicate that the relationship between vitamin D deficiency and cardiometabolic diseases is unlikely to merely reflect obesity-related pathomechanisms. [ABSTRACT FROM AUTHOR]

Objective: To study the association between socioeconomic status (SES) and annual relative change in anthropometric markers in the general German adult population.Methods: Longitudinal data of 56,556 participants aged 18-83 years from seven population-based German cohort studies (CARLA, SHIP, KORA, DEGS, EPIC-Heidelberg, EPIC-Potsdam, PopGen) were analyzed by meta-analysis using a random-effects model. The indicators of SES were education and household income.Results: On average, all participants gained weight and increased their waist circumference over the study's follow-up period. Men and women in the low education group had a 0.1 percentage points greater annual increase in weight (95% CI men: 0.06-0.20; and women: 0.06-0.12) and waist circumference (95% CI men: 0.01-0.45; and women: 0.05-0.22) than participants in the high education group. Women with low income had a 0.1 percentage points higher annual increase in weight (95% CI 0.00-0.15) and waist circumference (95% CI 0.00-0.14) than women with high income. No association was found for men between income and obesity markers.Conclusions: Participants with lower SES (education and for women also income) gained more weight and waist circumference than those with higher SES. These results underline the necessity to evaluate the risk of weight gain based on SES to develop more effective preventive measures. [ABSTRACT FROM AUTHOR]

The article discusses the study that determined associations between proximity of residences to green space and senior service centers, and healthy aging aspects of self-rated physical constitution, disability, and health-related quality of life of Augsburg, Germany residents aged at least 65. Topics discussed include no clear association found between distances of residential environment to closest green space or senior service center, as well as in aspects of health aging.

Background: Excess body weight is a major risk factor for cardiometabolic diseases. The complex molecular mechanisms of body weight change-induced metabolic perturbations are not fully understood. Specifically, in-depth molecular characterization of long-term body weight change in the general population is lacking. Here, we pursued a multi-omic approach to comprehensively study metabolic consequences of body weight change during a seven-year follow-up in a large prospective study. Methods: We used data from the population-based Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 cohort. At follow-up (F4), two-platform serum metabolomics and whole blood gene expression measurements were obtained for 1,631 and 689 participants, respectively. Using weighted correlation network analysis, omics data were clustered into modules of closely connected molecules, followed by the formation of a partial correlation network from the modules. Association of the omics modules with previous annual percentage weight change was then determined using linear models. In addition, we performed pathway enrichment analyses, stability analyses, and assessed the relation of the omics modules with clinical traits. Results: Four metabolite and two gene expression modules were significantly and stably associated with body weight change (P-values ranging from 1.9 x 10-4 to 1.2 x 10-24). The four metabolite modules covered major branches of metabolism, with VLDL, LDL and large HDL subclasses, triglycerides, branched-chain amino acids and markers of energy metabolism among the main representative molecules. One gene expression module suggests a role of weight change in red blood cell development. The other gene expression module largely overlaps with the lipid-leukocyte (LL) module previously reported to interact with serum metabolites, for which we identify additional co-expressed genes. The omics modules were interrelated and showed cross-sectional associations with clinical traits. Moreover, weight gain and weight loss showed largely opposing associations with the omics modules. Conclusions: Long-term weight change in the general population globally associates with serum metabolite concentrations. An integrated metabolomics and transcriptomics approach improved the understanding of molecular mechanisms underlying the association of weight gain with changes in lipid and amino acid metabolism, insulin sensitivity, mitochondrial function as well as blood cell development and function. [ABSTRACT FROM AUTHOR]

Background: Pain is a common symptom in patients with amyotrophic lateral sclerosis (ALS). Coping plays a central role in adjustment to pain. Objective: This study evaluates the use of different pain coping strategies in patients with ALS and investigates the interplay of maladaptive coping, and the patient's affective state and pain. Methods: One hundred and fifty ALS patients from three German outpatient clinics completed the Brief Pain Inventory (BPI), the ALS-Functional Rating Scale-Extension (ALSFRS-EX), the ALS Depression Inventory (ADI-12), the subscale "emotional functioning" of the ALS Assessment Questionnaire (ALSAQ-40) and the Coping Strategies Questionnaire (CSQ). Based upon the results of correlational analyses, multiple regression analyses were performed to identify predictors of pain severity and to explore factors contributing to maladaptive coping. Results: Pain was prevalent in 56% (n = 84) of the patients. Patients applied different adaptive coping strategies as well as the maladaptive strategy "catastrophizing". Regression analysis indicated that the CSQ-subscale "catastrophizing" significantly predicted pain intensity, explaining 34.0% of the variance (p < 0.001). Pain-related catastrophizing was associated with higher pain-related functional impairments and worse emotional functioning. The ADI-12 sum score as an indicator for depressive symptoms contributed significantly to the maladaptive coping strategy "catastrophizing" (p < 0.001) and explained 40.8% of the variance. Conclusion: Patients with ALS apply different strategies to cope with pain. Catastrophizing is an important determinant of higher pain intensity ratings and is associated with higher pain interferences and decreased emotional well-being. Pain-related catastrophizing is promoted by depressive symptoms. Catastrophizing and depressive symptoms thus represent important targets of individualized pain-management strategies. [ABSTRACT FROM AUTHOR]

Background: Although pain is common in amyotrophic lateral sclerosis (ALS) and an effectively treatable symptom, it is widely under-recognized and undertreated. This study investigates epidemiological and clinical characteristics of pain, its impact and pharmacological treatment in ALS patients. In addition, opportunities for further optimization of pain therapy need to be identified. Methods: Patients from three German ALS outpatient clinics were asked to complete the Brief Pain Inventory and the ALS Functional Rating Scale—Extension and to participate in semi-structured telephone interviews. Results: Of the 150 study participants, 84 patients reported pain. Pain occurred across all disease stages, predominantly in the neck, back and lower extremities. It was described with a broad spectrum of pain descriptors and mostly interfered with activity-related functions. Of the 84 pain patients, 53.8% reported an average pain intensity ≥4 on the numerical rating scale (NRS), indicating pain of at least moderate intensity, and 64.3% used pain medication. Irrespective of the medication type, 20.4% of them had no sufficient pain relief. Thirteen out of 30 patients without pain medication reported an average NRS value ≥4. Eleven of them—mainly in the context of high pain interference with daily functions—were supposed to benefit from adequate pain therapy. However, many patients had relevant concerns and misconceptions about pain therapy. Conclusion: Given the frequency, extent and multi-faceted impact of pain, it is necessary to systematically assess pain throughout the disease course. Potentials to optimize pain therapy were seen in the subset of patients with insufficient pain relief despite medication and in those patients without pain medication but high pain interference. However, there is a need to respond to patients' barriers to pain therapy. [ABSTRACT FROM AUTHOR]

Background: Dyspnea is frequent in amyotrophic lateral sclerosis (ALS) and one of the most bothersome symptoms. The recently developed Dyspnea-ALS-Scale (DALS-15) is a disease-specific patient-reported outcome to detect and quantify dyspnea.Objectives: To analyze in a case-based approach the diagnostic and clinical implications and the benefit of the DALS-15 for individual patients in daily clinical routine.Methods: Dyspnea was assessed by the 15-item comprising DALS-15 in two patients with ALS. Spirometry was performed and blood gases were analyzed. Results were evaluated in the clinical context of the respective patients.Results: In one patient the presence of dyspnea detected by the DALS-15 indicated noninvasive ventilation (NIV) although forced vital capacity (FVC) and blood gas analysis were well preserved. After NIV implementation, the DALS-15 was helpful to determine the patient's need for medication, the timing of NIV titration and the adaptation of NIV sessions. In another patient, who was anarthric and no longer able to perform spirometry due to severe bulbar impairment, the DALS-15 allowed a standardized assessment of dyspnea-related distress independently of bulbar dysfunction.Conclusion: The DALS-15 provides a deeper insight into the respiratory status of individual patients. It helps to diagnose respiratory impairment in patients in whom NIV should be considered although FVC and blood gas results do not reveal indication for NIV. It is also valuable for the guidance of patients in later stages of respiratory impairment when NIV is already implemented, and in patients with severe bulbar dysfunction. The DALS-15 can improve specific symptom management and coordination of care and therefore has the potential to optimize individual treatment in ALS patients with dyspnea. [ABSTRACT FROM AUTHOR]

Background: Excess body weight is a major risk factor for cardiometabolic diseases. The complex molecular mechanisms of body weight change-induced metabolic perturbations are not fully understood. Specifically, in-depth molecular characterization of long-term body weight change in the general population is lacking. Here, we pursued a multi-omic approach to comprehensively study metabolic consequences of body weight change during a seven-year follow-up in a large prospective study.Methods: We used data from the population-based Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 cohort. At follow-up (F4), two-platform serum metabolomics and whole blood gene expression measurements were obtained for 1,631 and 689 participants, respectively. Using weighted correlation network analysis, omics data were clustered into modules of closely connected molecules, followed by the formation of a partial correlation network from the modules. Association of the omics modules with previous annual percentage weight change was then determined using linear models. In addition, we performed pathway enrichment analyses, stability analyses, and assessed the relation of the omics modules with clinical traits.Results: Four metabolite and two gene expression modules were significantly and stably associated with body weight change (P-values ranging from 1.9 × 10(-4) to 1.2 × 10(-24)). The four metabolite modules covered major branches of metabolism, with VLDL, LDL and large HDL subclasses, triglycerides, branched-chain amino acids and markers of energy metabolism among the main representative molecules. One gene expression module suggests a role of weight change in red blood cell development. The other gene expression module largely overlaps with the lipid-leukocyte (LL) module previously reported to interact with serum metabolites, for which we identify additional co-expressed genes. The omics modules were interrelated and showed cross-sectional associations with clinical traits. Moreover, weight gain and weight loss showed largely opposing associations with the omics modules.Conclusions: Long-term weight change in the general population globally associates with serum metabolite concentrations. An integrated metabolomics and transcriptomics approach improved the understanding of molecular mechanisms underlying the association of weight gain with changes in lipid and amino acid metabolism, insulin sensitivity, mitochondrial function as well as blood cell development and function. [ABSTRACT FROM AUTHOR]