The involvement of cerebrospinal fluid and lymphatic drainage in chronic fatigue syndrome (CFS/ME)

A novel osteopathic treatment has been discovered during the clinical practice of the authorwhich alleviates many of the symptoms of chronic fatigue syndrome (CFS) known in theUK as CFS/ME. The efficacy of this manual approach was tested using two separateclinical trials. The first examined the change in the symptoms following a year of treatment.The second repeated the first study and examined the possible mechanisms of theimprovement. The studies were designed to develop a greater understanding of the disorder,for which there is much scientific uncertainty regarding the cause, diagnosis and treatment.Phase 1 of the research trials included self report questionnaires to examine overallsymptom change. With post-exercise fatigue being a major symptom of CFS/ME, thetreatment protocol was best evaluated by determining its effects on muscle function whichwas analysed utilising isometric testing of the knee extensor muscles measuring the impulsetorque.The second trial, which included the same self report questionnaires assessing symptomrelief as in the initial trial, was divided into two parallel phases. Phase 2 primarily took theform of brain analysis using magnetic resonance imaging (MRI) to confirm if brainabnormalities seen in previous research were found in sufferers of CFS/ME. No cerebralabnormality was detected in the patient group. Central lymph scans were also carried outshowing a possible trend of enlargement in CFS/ME sufferers. In the other part, phase 3,isometric tests were repeated with more accurate equipment than in phase 1. IntegratedEMG and median frequency of the power spectrum were measured using surfaceelectromyography (sEMG).Overall this study has provided strong evidence that an important component of CFS/MEinvolves a disturbance of lymphatic drainage of the brain and muscles. The novelosteopathic treatment developed by the author has been statistically validated in bothphases of the study, emphasising the need to focus future research on the biomechanicalaspectso f this disorder

6D supergravity without tensor multiplets

We systematically investigate the finite set of possible gauge groups and matter content for N = 1 supergravity theories in six dimensions with no tensor multiplets, focusing on nonabelian gauge groups which are a product of SU(N) factors. We identify a number of models which obey all known low-energy consistency conditions, but which have no known string theory realization. Many of these models contain novel matter representations, suggesting possible new string theory constructions. Many of the most exotic matter structures arise in models which precisely saturate the gravitational anomaly bound on the number of hypermultiplets. Such models have a rigid symmetry structure, in the sense that there are no moduli which leave the full gauge group unbroken.Comment: 31 pages, latex; v2, v3: minor corrections, references adde

Effect of the consumption of a fermented dairy product containing Bifidobacterium lactis DN-173 010 on constipation in childhood: a multicentre randomised controlled trial (NTRTC: 1571)

<p>Abstract</p> <p>Background</p> <p>Constipation is a frustrating symptom affecting 3% of children worldwide. Randomised controlled trials show that both polyethylene glycol and lactulose are effective in increasing defecation frequency in children with constipation. However, in 30–50%, these children reported abdominal pain, bloating, flatulence, diarrhoea, nausea and bad taste of the medication. Two recent studies have shown that the fermented dairy product containing <it>Bifidobacterium lactis </it>strain DN-173 010 is effective in increasing stool frequency in constipation-predominant irritable bowel syndrome patients with a defecation frequency < 3/week and in constipated women with a defecation frequency < 3/week. Goal of this study is to determine whether this fermented dairy product is effective in the treatment of constipated children with a defecation frequency < 3/week.</p> <p>Methods/design</p> <p>It is a two nation (The Netherlands and Poland) double-blind, placebo-controlled randomised multicentre trial in which 160 constipated children (age 3–16 years) with a defecation frequency <3/week will be randomly allocated to consume a fermented dairy product containing <it>Bifidobacterium lactis </it>DN-173 010 or a control product, twice a day, for 3 weeks. During the study all children are instructed to try to defecate on the toilet for 5–10 minutes after each meal (3 times a day) and daily complete a standardized bowel diary. Primary endpoint is stool frequency. Secondary endpoints are stool consistency, faecal incontinence frequency, pain during defecation, digestive symptoms (abdominal pain, flatulence), adverse effects (nausea, diarrhoea, bad taste) and intake of rescue medication (Bisacodyl). Rate of success and rate of responders are also evaluated, with success defined as ≥ 3 bowel movements per week and ≤1 faecal incontinence episode over the last 2 weeks of product consumption and responder defined as a subject reporting a stool frequency ≥ 3 on the last week of product consumption. To demonstrate that the success percentage in the intervention group will be 35% and the success percentage in the control group (acidified milk without ferments, toilet training, bowel diary) will be 15%, with alpha 0.05 and power 80%, a total sample size of 160 patients was calculated.</p> <p>Conclusion</p> <p>This study is aimed to show that the fermented dairy product containing <it>Bifidobacterium lactis </it>strain DN-173 010 is effective in increasing stool frequency after 3 weeks of product consumption in children with functional constipation and a defecation frequency < 3/week.</p

The consistency between treatments provided to nursing facility residents and orders on the physician orders for lifesustaining treatment form. J Am Geriatr Soc

OBJECTIVES: To evaluate the consistency between treatments provided and Physician Orders for Life-Sustaining Treatment (POLST) orders. DESIGN: Retrospective chart abstraction. SETTING: Stratified, random sample of 90 nursing facilities in Oregon, Wisconsin, and West Virginia. PARTICIPANTS: Eight hundred seventy living and deceased nursing facility residents aged 65 and older with a minimum 60-day stay. MEASUREMENTS: Chart data about POLST form orders and related treatments over a 60-day period were abstracted. Decision rules were created to determine whether the rationale for each treatment was consistent with POLST orders. RESULTS: Most residents (85.2%) had the same POLST form in place during the review period. A majority of treatments provided to residents with orders for comfort measures only (74.3%) and limited antibiotics (83.3%) were consistent with POLST orders because they were primarily comfort focused rather than life-prolonging, but antibiotics were provided to 32.1% of residents with orders for no antibiotics. Overall consistency rates between treatments and POLST orders were high for resuscitation (98%), medical interventions (91.1%), and antibiotics (92.9%) and modest for feeding tubes (63.6%). In all, POLST orders were consistent with treatments provided 94.0% of the time. CONCLUSION: With the exception of feeding tubes and antibiotic use in residents with orders for no antibiotics, the use of medical treatments was nearly always consistent with POLST orders to provide or withhold life-sustaining interventions. The POLST program is a useful tool for ensuring that the treatment preferences of nursing facility residents are honored. J Am Geriatr Soc 59:2091-2099, 2011. Key words: ethics; end of life; comfort care; palliative care; nursing facility A primary goal of advance care planning is to ensure that treatments are consistent with patient preferences near the end of life. Advance directives have been promoted as an important advance care planning tool that enables individuals to record their preferences to guide treatment decisions in the event of incapacitation, but research suggests that advance directives are generally ineffective at ensuring that treatment preferences are honored because of numerous limitations. 1-3 An alternative approach is the use of medical orders such as do not resuscitate (DNR) that communicate preferences in a format that other healthcare professionals can follow. However, such orders typically focus on one type of life-sustaining treatment and do not address the broad range of potential treatments that may be needed

The effect of massage on localized lumbar muscle fatigue

BACKGROUND: There is not enough evidence to support the efficacy of massage for muscle fatigue despite wide utilization of the modality in various clinical settings. This study investigated the influence of massage application on localized back muscle fatigue. METHODS: Twenty-nine healthy subjects participated in two experimental sessions (massage and rest conditions). On each test day, subjects were asked to lie in the prone position on a treatment table and perform sustained back extension for 90 seconds. Subjects then either received massage on the lumbar region or rested for a 5 minute duration, then repeated the back extension movement. The median frequency (MDF), mean power frequency (MNF), and root mean square (RMS) amplitude of electromyographic signals during the 90 second sustained lumbar muscle contraction were analyzed. The subjective feeling of fatigue was then evaluated using the Visual Analogue Scale (VAS). RESULTS: MDF and MNF significantly declined with time under all conditions. There was no significant difference in MDF, MNF or RMS value change between before and after massage, or between rest and massage conditions. There was a significant increase in fatigue VAS at the end of the 2(nd) back extension with rest condition. There was a significant difference in fatigue VAS change between massage and rest condition. CONCLUSIONS: A significant difference was observed between massage and rest condition on VAS for muscle fatigue. On EMG analysis, there were no significant differences to conclude that massage stimulation influenced the myoelectrical muscle fatigue, which is associated with metabolic and electrical changes

Awareness of genetic risk in the Dominantly Inherited Alzheimer Network (DIAN)

Introduction: Although some members of families with autosomal dominant Alzheimer's disease mutations learn their mutation status, most do not. How knowledge of mutation status affects clinical disease progression is unknown. This study quantifies the influence of mutation awareness on clinical symptoms, cognition, and biomarkers. / Methods: Mutation carriers and non‐carriers from the Dominantly Inherited Alzheimer Network (DIAN) were stratified based on knowledge of mutation status. Rates of change on standard clinical, cognitive, and neuroimaging outcomes were examined. / Results: Mutation knowledge had no associations with cognitive decline, clinical progression, amyloid deposition, hippocampal volume, or depression in either carriers or non‐carriers. Carriers who learned their status mid‐study had slightly higher levels of depression and lower cognitive scores. / Discussion: Knowledge of mutation status does not affect rates of change on any measured outcome. Learning of status mid‐study may confer short‐term changes in cognitive functioning, or changes in cognition may influence the determination of mutation status

Pattern and degree of individual brain atrophy predicts dementia onset in dominantly inherited Alzheimer's disease

Introduction: Asymptomatic and mildly symptomatic dominantly inherited Alzheimer's disease mutation carriers (DIAD-MC) are ideal candidates for preventative treatment trials aimed at delaying or preventing dementia onset. Brain atrophy is an early feature of DIAD-MC and could help predict risk for dementia during trial enrollment. Methods: We created a dementia risk score by entering standardized gray-matter volumes from 231 DIAD-MC into a logistic regression to classify participants with and without dementia. The score's predictive utility was assessed using Cox models and receiver operating curves on a separate group of 65 DIAD-MC followed longitudinally. Results: Our risk score separated asymptomatic versus demented DIAD-MC with 96.4% (standard error = 0.02) and predicted conversion to dementia at next visit (hazard ratio = 1.32, 95% confidence interval [CI: 1.15, 1.49]) and within 2 years (area under the curve = 90.3%, 95% CI [82.3%–98.2%]) and improved prediction beyond established methods based on familial age of onset. Discussion: Individualized risk scores based on brain atrophy could be useful for establishing enrollment criteria and stratifying DIAD-MC participants for prevention trials

Segregation of functional networks is associated with cognitive resilience in Alzheimer's disease

Cognitive resilience is an important modulating factor of cognitive decline in Alzheimer's disease, but the functional brain mechanisms that support cognitive resilience remain elusive. Given previous findings in normal aging, we tested the hypothesis that higher segregation of the brain's connectome into distinct functional networks represents a functional mechanism underlying cognitive resilience in Alzheimer's disease. Using resting-state functional MRI, we assessed both resting-state-fMRI global system segregation, i.e. the balance of between-network to within-network connectivity, and the alternate index of modularity Q as predictors of cognitive resilience. We performed all analyses in two independent samples for validation: First, we included 108 individuals with autosomal dominantly inherited Alzheimer's disease and 71 non-carrier controls. Second, we included 156 amyloid-PET positive subjects across the spectrum of sporadic Alzheimer's disease as well as 184 amyloid-negative controls. In the autosomal dominant Alzheimer's disease sample, disease severity was assessed by estimated years from symptom onset. In the sporadic Alzheimer's sample, disease stage was assessed by temporal-lobe tau-PET (i.e. composite across Braak stage I & III regions). In both samples, we tested whether the effect of disease severity on cognition was attenuated at higher levels of functional network segregation. For autosomal dominant Alzheimer's disease, we found higher fMRI-assessed system segregation to be associated with an attenuated effect of estimated years from symptom onset on global cognition (p = 0.007). Similarly, for sporadic Alzheimer's disease patients, higher fMRI-assessed system segregation was associated with less decrement in global cognition (p = 0.001) and episodic memory (p = 0.004) per unit increase of temporal lobe tau-PET. Confirmatory analyses using the alternate index of modularity Q revealed consistent results. In conclusion, higher segregation of functional connections into distinct large-scale networks supports cognitive resilience in Alzheimer's disease

Location of pathogenic variants in PSEN1 impacts progression of cognitive, clinical, and neurodegenerative measures in autosomal-dominant Alzheimer's disease

Although pathogenic variants in PSEN1 leading to autosomal-dominant Alzheimer disease (ADAD) are highly penetrant, substantial interindividual variability in the rates of cognitive decline and biomarker change are observed in ADAD. We hypothesized that this interindividual variability may be associated with the location of the pathogenic variant within PSEN1. PSEN1 pathogenic variant carriers participating in the Dominantly Inherited Alzheimer Network (DIAN) observational study were grouped based on whether the underlying variant affects a transmembrane (TM) or cytoplasmic (CY) protein domain within PSEN1. CY and TM carriers and variant non-carriers (NC) who completed clinical evaluation, multimodal neuroimaging, and lumbar puncture for collection of cerebrospinal fluid (CSF) as part of their participation in DIAN were included in this study. Linear mixed effects models were used to determine differences in clinical, cognitive, and biomarker measures between the NC, TM, and CY groups. While both the CY and TM groups were found to have similarly elevated Aβ compared to NC, TM carriers had greater cognitive impairment, smaller hippocampal volume, and elevated phosphorylated tau levels across the spectrum of pre-symptomatic and symptomatic phases of disease as compared to CY, using both cross-sectional and longitudinal data. As distinct portions of PSEN1 are differentially involved in APP processing by γ-secretase and the generation of toxic β-amyloid species, these results have important implications for understanding the pathobiology of ADAD and accounting for a substantial portion of the interindividual heterogeneity in ongoing ADAD clinical trials