Dysphagia affecting quality of life in cerebellar ataxia - a large survey

Dysphagia is a common symptom in neurodegenerative disorders and is generally associated with increased mortality. In the clinical care setting of ataxia patients, no systematical and standardized assessment of dysphagia is employed. Its impact on patients' health-related quality of life is not well understood. To assess the impact of dysphagia in ataxia patients on diet, body weight, and health-related quality of life. We conducted a large survey using self-reported questionnaires for swallowing-related quality of life (Swal-QOL) and a food frequency list in combination with retrospective clinical data of 119 patients with cerebellar ataxia treated in the neurological outpatient clinic of a large German university hospital. Seventeen percent of ataxia patients suffered from dysphagia based on the Swal-QOL score. Less than 1% of all patients reported dysphagia as one of their most disabling symptoms. Dysphagia was associated with unintentional weight loss (p = 0.02) and reduced health-related quality of life (p = 0.01) but did not affect individual nutritional habits (p > 0.05; Chi-squared test). Dysphagia is a relevant symptom in cerebellar ataxia. A systematic screening for dysphagia in patients with cerebellar ataxia would be desirable to enable early diagnosis and treatment

Dysphagia Affecting Quality of Life in Cerebellar Ataxia—a Large Survey

Dysphagia is a common symptom in neurodegenerative disorders and is generally associated with increased mortality. In the clinical care setting of ataxia patients, no systematical and standardized assessment of dysphagia is employed. Its impact on patients’ health-related quality of life is not well understood. To assess the impact of dysphagia in ataxia patients on diet, body weight, and health-related quality of life. We conducted a large survey using self-reported questionnaires for swallowing-related quality of life (Swal-QOL) and a food frequency list in combination with retrospective clinical data of 119 patients with cerebellar ataxia treated in the neurological outpatient clinic of a large German university hospital. Seventeen percent of ataxia patients suffered from dysphagia based on the Swal-QOL score. Less than 1% of all patients reported dysphagia as one of their most disabling symptoms. Dysphagia was associated with unintentional weight loss (p = 0.02) and reduced health-related quality of life (p = 0.01) but did not affect individual nutritional habits (p > 0.05; Chi-squared test). Dysphagia is a relevant symptom in cerebellar ataxia. A systematic screening for dysphagia in patients with cerebellar ataxia would be desirable to enable early diagnosis and treatment

Effect of a probiotic on blood pressure in grade 1 hypertension (HYPRO): protocol of a randomized controlled study

BACKGROUND: Arterial hypertension is a major risk factor for cardiovascular disease and leads to target organ damage including stroke, heart failure, and kidney disease. About 1.5 billion people worldwide have hypertension, and it is estimated that it causes about 8 million deaths each year. Although there are several drugs available to lower blood pressure (BP), a great proportion of treated patients does not reach recommended treatment targets. Typical antihypertensive drugs target the vessels, the kidneys, and the heart. However, our gut microbiota also influences cardiovascular health, and gut dysbiosis is associated with hypertension. In this study protocol, we investigate the potential BP-lowering effect of a probiotic in patients with grade 1 hypertension. METHODS: This study is an exploratory, randomized, double-blind, placebo-controlled, parallel-group study. One hundred ten patients with grade 1 hypertension (treated or untreated) will be randomized to either the probiotic Vivomixx® or placebo. The primary endpoint is the nocturnal systolic BP measured by ambulatory blood pressure monitoring after 8 weeks adjusted for the baseline value. The secondary endpoints are changes from baseline in nocturnal diastolic BP, antihypertensive medication, fecal microbiome composition, fecal and serum metabolome, immune cell phenotypes, glucose variability after three standardized breakfasts, and health-related quality of life (PROMIS-29). We also assess the safety profile of the intervention. DISCUSSION: We postulate that various administrated bacteria (Lactobacilli, Bifidobacteria, and Streptococcus thermophilus) convert dietary components into active metabolites that positively affect immune cell function. A reduction of pro-inflammatory immune cell function could promote a BP-lowering effect. TRIAL REGISTRATION: ClinicalTrials.gov NCT03906578 . Registered on 08 April 2019

Metabolic, mental and immunological effects of normoxic and hypoxic training in multiple sclerosis patients: a pilot study

Background: Physical activity might attenuate inflammation and neurodegeneration in multiple sclerosis (MS). Erythropoietin, which is produced upon exposure to hypoxia, is thought to act as a neuroprotective agent in MS. Therefore, we studied the effects of intermittent hypoxic training on activity energy expenditure, maximal workload, serum erythropoietin, and immunophenotype focusing on regulatory and IL-17A-producing T cells. Methods: We assigned 34 relapsing-remitting MS patients within a randomized, single blind, parallel-group study to either normoxic (NO) or hypoxic (HO) treadmill training, both 3 times/week for 1 h over 4 weeks (Clinicaltrials.gov identifier: NCT02509897). Before and after training, activity energy expenditure (metabolic chamber), maximal workload (incremental treadmill test), walking ability, depressive symptoms (Beck Depression Inventory I), serum erythropoietin concentrations, and immunophenotype of peripheral blood mononuclear cells (PBMCs) were assessed. Results: Energy expenditure did not change due to training in both groups, but was rather fueled by fat than by carbohydrate oxidation after HO training (P = 0.002). Maximal workload increased by 40 Watt and 42 Watt in the NO and HO group, respectively (both P < 0.0001). Distance patients walked in 6 min increased by 25 m and 27 m in the NO and HO group, respectively (NO P = 0.02; HO P = 0.01). Beck Depression Inventory score markedly decreased in both groups (NO P = 0.03; HO P = 0.0003). NO training shifted Treg subpopulations by increasing and decreasing the frequency of CD39(+) and CD31(+) Tregs, respectively, and decreased IL-17A-producing CD4(+) cells. HO training provoked none of these immunological changes. Erythropoietin concentrations were within normal range and did not significantly change in either group. Conclusion: 4 weeks of moderate treadmill training had considerable effects on fitness level and mood in MS patients, both under normoxic and hypoxic conditions. Additionally, NO training improved Th17/Treg profile and HO training improved fatty acid oxidation during exercise. These effects could not be attributed to an increase of erythropoietin

Metabolic, Mental and Immunological Effects of Normoxic and Hypoxic Training in Multiple Sclerosis Patients: A Pilot Study

Background: Physical activity might attenuate inflammation and neurodegeneration in multiple sclerosis (MS). Erythropoietin, which is produced upon exposure to hypoxia, is thought to act as a neuroprotective agent in MS. Therefore, we studied the effects of intermittent hypoxic training on activity energy expenditure, maximal workload, serum erythropoietin, and immunophenotype focusing on regulatory and IL-17A-producing T cells.Methods: We assigned 34 relapsing-remitting MS patients within a randomized, single blind, parallel-group study to either normoxic (NO) or hypoxic (HO) treadmill training, both 3 times/week for 1 h over 4 weeks (Clinicaltrials.gov identifier: NCT02509897). Before and after training, activity energy expenditure (metabolic chamber), maximal workload (incremental treadmill test), walking ability, depressive symptoms (Beck Depression Inventory I), serum erythropoietin concentrations, and immunophenotype of peripheral blood mononuclear cells (PBMCs) were assessed.Results: Energy expenditure did not change due to training in both groups, but was rather fueled by fat than by carbohydrate oxidation after HO training (P = 0.002). Maximal workload increased by 40 Watt and 42 Watt in the NO and HO group, respectively (both P &lt; 0.0001). Distance patients walked in 6 min increased by 25 m and 27 m in the NO and HO group, respectively (NO P = 0.02; HO P = 0.01). Beck Depression Inventory score markedly decreased in both groups (NO P = 0.03; HO P = 0.0003). NO training shifted Treg subpopulations by increasing and decreasing the frequency of CD39+ and CD31+ Tregs, respectively, and decreased IL-17A-producing CD4+ cells. HO training provoked none of these immunological changes. Erythropoietin concentrations were within normal range and did not significantly change in either group.Conclusion: 4 weeks of moderate treadmill training had considerable effects on fitness level and mood in MS patients, both under normoxic and hypoxic conditions. Additionally, NO training improved Th17/Treg profile and HO training improved fatty acid oxidation during exercise. These effects could not be attributed to an increase of erythropoietin.Clinical Trial Registration: ClinicalTrials.gov; NCT02509897; http://www.clinicaltrials.go

Altered expression of cyclin A 1 in muscle of patients with facioscapulohumeral muscle dystrophy (FSHD-1)

Objectives Cyclin A1 regulates cell cycle activity and proliferation in somatic and germ-line cells. Its expression increases in G1/S phase and reaches a maximum in G2 and M phases. Altered cyclin A1 expression might contribute to clinical symptoms in facioscapulohumeral muscular dystrophy (FSHD). Methods Muscle biopsies were taken from the Vastus lateralis muscle for cDNA microarray, RT-PCR, immunohistochemistry and Western blot analyses to assess RNA and protein expression of cyclin A1 in human muscle cell lines and muscle tissue. Muscle fibers diameter was calculated on cryosections to test for hypertrophy. Results cDNA microarray data showed specifically elevated cyclin A1 levels in FSHD vs. other muscular disorders such as caveolinopathy, dysferlinopathy, four and a half LIM domains protein 1 deficiency and healthy controls. Data could be confirmed with RT-PCR and Western blot analysis showing up-regulated cyclin A1 levels also at protein level. We found also clear signs of hypertrophy within the Vastus lateralis muscle in FSHD-1 patients. Conclusions In most somatic human cell lines, cyclin A1 levels are low. Overexpression of cyclin A1 in FSHD indicates cell cycle dysregulation in FSHD and might contribute to clinical symptoms of this disease

Glassy low-energy spin fluctuations and anisotropy gap in La_1.88Sr_0.12CuO₄

We present high-resolution triple-axis neutron scattering studies of the high-temperature superconductor La1.88Sr0.12CuO4 (Tc=27 K). The temperature dependence of the low-energy incommensurate magnetic fluctuations reveals distinctly glassy features. The glassiness is confirmed by the difference between the ordering temperature TN ~ Tc inferred from elastic neutron scattering and the freezing temperature Tf ~ 11 K obtained from muon spin rotation studies. The magnetic field independence of the observed excitation spectrum as well as the observation of a partial suppression of magnetic spectral weight below 0.75 meV for temperatures smaller than Tf, indicate that the stripe frozen state is capable of supporting a spin anisotropy gap, of a magnitude similar to that observed in the spin and charge stripe ordered ground state of La1.875Ba0.125CuO4. The difference between TN and Tf implies that the significant enhancement in a magnetic field of nominally elastic incommensurate scattering is caused by strictly in-elastic scattering -- at least in the temperature range between Tf and Tc -- which is not resolved in the present experiment. Combining the results obtained from our study of La1.88Sr0.12CuO4 with a critical reappraisal of published neutron scattering work on samples with chemical composition close to p=0.12, where local probes indicate a sharp maximum in Tf(p), we arrive at the view that the low-energy fluctuations are strongly dependent on composition in this regime, with anisotropy gaps dominating only sufficiently close to p=0.12 and superconducting spin gaps dominating elsewhere.Comment: 8 pages, 4 figure

Increased salt intake decreases diet-induced thermogenesis in healthy volunteers: a randomized placebo-controlled study

High salt intake ranks among the most important risk factors for noncommunicable diseases. Western diets, which are typically high in salt, are associated with a high prevalence of obesity. High salt is thought to be a potential risk factor for obesity independent of energy intake, although the underlying mechanisms are insufficiently understood. A high salt diet could influence energy expenditure (EE), specifically diet-induced thermogenesis (DIT), which accounts for about 10% of total EE. We aimed to investigate the influence of high salt on DIT. In a randomized, double-blind, placebo-controlled, parallel-group study, 40 healthy subjects received either 6 g/d salt (NaCl) or placebo in capsules over 2 weeks. Before and after the intervention, resting EE, DIT, body composition, food intake, 24 h urine analysis, and blood pressure were obtained. EE was measured by indirect calorimetry after a 12 h overnight fast and a standardized 440 kcal meal. Thirty-eight subjects completed the study. Salt intake from foods was 6 g/d in both groups, resulting in a total salt intake of 12 g/d in the salt group and 6 g/d in the placebo group. Urine sodium increased by 2.29 g/d (p < 0.0001) in the salt group, indicating overall compliance. The change in DIT differed significantly between groups (placebo vs. salt, p = 0.023). DIT decreased by 1.3% in the salt group (p = 0.048), but increased by 0.6% in the placebo group (NS). Substrate oxidation indicated by respiratory exchange ratio, body composition, resting blood pressure, fluid intake, hydration, and urine volume did not change significantly in either group. A moderate short-term increase in salt intake decreased DIT after a standardized meal. This effect could at least partially contribute to the observed weight gain in populations consuming a Western diet high in salt

Indigenous identity, natural resources, and contentious politics in Bolivia: a disaggregated conflict analysis; 2000-2011

How do natural resources and ethnic identity interact to incite or to mitigate social conflict? This article argues that high-value natural resources can act as an important catalyst for the politicization of ethnic, specifically indigenous identity, and contribute to social conflict as they limit the malleability of identity frames and raise the stakes of confrontations. We test this argument using unique subnational data from Bolivian provinces. Drawing on Bolivian newspaper reports, we code conflict events for all of the 112 provinces from 2000 to 2011. We join this conflict data with information on local ethnic composition from the census, the political representation of ethnic groups at the national level, as well as geo-spatial information on gas deposits. Using time-series cross-sectional count models, we show a significant conflict-promoting effect of the share of indigenous people in provinces with gas reserves, but not without

Photoperiodic control of seasonal growth is mediated by ABA acting on cell-cell communication

In temperate and boreal ecosystems, seasonal cycles of growth and dormancy allow perennial plants to adapt to winter conditions. We show, in hybrid aspen trees, that photoperiodic regulation of dormancy is mechanistically distinct from autumnal growth cessation. Dormancy sets in when symplastic intercellular communication through plasmodesmata is blocked by a process dependent on the phytohormone abscisic acid. The communication blockage prevents growth-promoting signals from accessing the meristem. Thus, precocious growth is disallowed during dormancy. The dormant period, which supports robust survival of the aspen tree in winter, is due to loss of access to growth-promoting signals