Wellness and Multiple Sclerosis: The National MS Society Establishes a Wellness Research Working Group and Research Priorities

Background: People with multiple sclerosis (MS) have identified “wellness” and associated behaviors as a high priority based on “social media listening” undertaken by the National MS Society (i.e. the Society). Objective: The Society recently convened a group that consisted of researchers with experience in MS and wellness-related research, Society staff members, and an individual with MS for developing recommendations regarding a wellness research agenda. Method: The members of the group engaged in focal reviews and discussions involving the state of science within three approaches for promoting wellness in MS, namely diet, exercise, and emotional wellness. Results: That process informed a group-mediated activity for developing and prioritizing research goals for wellness in MS. This served as a background for articulating the mission and objectives of the Society’s Wellness Research Working Group. Conclusion: The primary mission of the Wellness Research Working Group is the provision of scientific evidence supporting the application of lifestyle, behavioral, and psychosocial approaches for promoting optimal health of mind, body, and spirit (i.e. wellness) in people with MS as well as managing the disease and its consequences

Mouse Plasminogen Has Oxidized Phosphatidylcholine Adducts That Are Not Metabolized by Lipoprotein-Associated Phospholipase A2 under Basal Conditions

We previously showed that plasminogen (Plg) isolated from the plasma of normal human subjects contains 1–2 moles of oxidized phosphatidylcholine (oxPtdPC) adducts/mole of protein. Moreover, we suggested that these species are generated at the hepatic site and speculated that they may play a role in the reported cardiovascular pathogenicity of Plg. We aimed to determine whether mouse Plg also harbors linked oxPtdPCs and whether these molecules are metabolized by lipoprotein-associated phospholipase A2/PAF acetylhydrolase (Lp-PLA2/PAF-AH), an enzyme specific for hydrolysis of oxPtdPCs. We determined the total concentration of Plg in plasma samples from control (WT) and Lp-PLA2-deficient (KO) mice, we isolated Plg, and assessed its content of oxPtdPCs by immunoblot analyses. We also evaluated whether human recombinant Lp-PLA2 metabolized Plg-linked oxPtdPCs in vivo and in vitro. WT and KO mice expressed comparable levels (14.4–15.8 mg/dL) of plasma Plg, as determined by ELISA. We observed no differences in the content of oxPtdPC in Plg isolated from the two mouse strains and in parallel no changes in oxPtdPC content in mouse Plg following incubation with pure recombinant Lp-PLA2. Plg from mouse plasma contains oxPtdPC adducts that are not affected by the action of Lp-PLA2, suggesting that linkage to Plg protects oxPtdPCs from metabolism during their transport in the plasma. This modification may have important physio-pathological implications related to the function of Plg, oxPtdPCs, or both

Protective Roles for Fibrin, Tissue Factor, Plasminogen Activator Inhibitor-1, and Thrombin Activatable Fibrinolysis Inhibitor, but Not Factor XI, during Defense against the Gram-Negative Bacterium Yersinia enterocolitica

Septic infections dysregulate hemostatic pathways, prompting coagulopathy. Nevertheless, anticoagulant therapies typically fail to protect humans from septic pathology. The data reported here may help to explain this discrepancy by demonstrating critical protective roles for coagulation leading to fibrin deposition during host defense against the gram-negative bacterium Yersinia enterocolitica. After intraperitoneal inoculation with Y. enterocolitica, fibrinogen-deficient mice display impaired cytokine and chemokine production in the peritoneal cavity and suppressed neutrophil recruitment. Moreover, both gene-targeted fibrinogen-deficient mice and wild type mice treated with the anticoagulant coumadin display increased hepatic bacterial burden and mortality following either intraperitoneal or intravenous inoculation with Y. enterocolitica. Mice with low tissue factor (TF) activity succumb to yersiniosis with a phenotype similar to fibrin(ogen)-deficient mice, whereas factor XI (FXI)-deficient mice show wild type levels of resistance. Mice deficient in plasminogen activator inhibitor-1 (PAI-1) or thrombin activatable fibrinolysis inhibitor (TAFI) display modest phenotypes, but mice deficient in both PAI-1 and TAFI succumb to yersiniosis with a phenotype resembling fibrin(ogen)-deficient mice. These findings demonstrate critical protective roles for the TF-dependent extrinsic coagulation pathway during host defense against bacteria and caution that therapeutics targeting major thrombin-generating or anti-fibrinolytic pathways may disrupt fibrin-mediated host defense during gram-negative sepsis

Dietary responses to a multiple sclerosis diagnosis: a qualitative study

Background/objectives: Multiple sclerosis (MS) is an immune-mediated disease with no known cure and insufficient evidence to support a special therapeutic diet to alter symptom management or disease progression. Several studies have reported dietary changes made by people with MS, but there has been limited investigation into experiences surrounding diet in those recently diagnosed. This study explored responses to diet after a recent diagnosis of MS in people living in Western Australia. Subjects/methods: Eleven adults with MS (mean time since diagnosis 8 months) participated in semi-structured interviews focusing on responses to diet since MS diagnosis. Interviews were transcribed, coded and analysed using grounded theory principles. Results: Three theme responses emerged; (1) the perceived incompatibility of lack of/or generalised dietary advice with disease seriousness at the time of diagnosis; (2) extensive personal research and information seeking with difficulty judging credibility, and (3) self-experimentation with diet to either control MS symptoms or to cure MS. Conclusions: Given the seriousness of the disease, there is a perceived gap in dietary information provided at the time of diagnosis. Healthcare professionals should address concerns with alternative therapeutic diets advertised to treat or cure MS, and clearly convey the reasoning for the general healthy dietary recommendations. This would better align advice with the perceptions about the role of diet in MS, assist people with MS in need of information and minimise dietary self-experimentation. Future research should explore the importance of diet for those who have had MS for a longer period of time

Penerapan Metode Eksperimen untuk Meningkatkan Konsep Dasar Sains pada Anak Didik Kelompok A Tk Pkk Suruhwadang Kecamatan Kademangan Kabupaten Blitar

Tujuan penelitian ini adalah untuk memperoleh tentang kemampuan kognitif anak dalamhal konsep dasar sains dengan menggunakan metode eksperimen pada anak didik kelompokA TK PKK Suruhwadang sebelum dan sesudah dilakukan tindakan. Melakukan tindakanberupa penerapan metode eksperimen untuk meningkatkan kemampuan kognitif dalamkonsep dasar sains pada anak didik kelompok A TK PKK Suruhwadang. Mengetahui adatidaknya perbedaan kemampuan konsep dasar sains dengan menggunakan metodeeksperimen pada anak didik kelompok A TK PKK Suruhwadang antara sebelum dan setelahdilakukan tindakan. Rumusan masalah pada penitilian ini adalah apakah metode eksperimendapat meningkatkan kemampuan pemahaman konsep dasar sains pada anak didik kelompokA TK PKK Suruhwadang Kecamatan Kademangan Kabupaten Blitar. Untuk menjawabrumusan masalah digunakan jenis penelitian tindakan kelas (PTK) dengan model Kemmisdan Taggart melalui empat tahapan yaitu tahap perencanaan , pelaksanaan, observasi danrefleksiyang dilalui dengan dua siklus. Teknik pengumpulan data menggunakan teknikobservasi dan dokumentasi. Adapun instrumen yang digunakan adalah lembar observasikegiatan anak dan lembar observasi pembelajaran oleh guru.Hasil penelitian menunjukanbahwa kemampuan kognitif anak kelompok A pada konsep dasar sain pada pra penelitianmenunjukkan prosentase 56.25%. Setelah pelaksanaan siklus I tentang bidang kemampuankognitif pada konsep dasar sains menunjukkan 59% mengalami peningkatan .Setelahpelaksanaan siklus ke II naik menjadi 83%. Hal ini menunjukkan pelaksanaan siklus ke IItelah mencapai kriteria ketuntasan dan membuktikan bahwa dengan metode eksperimendapat meningkatkan kemampuan kognitif dalam konsep dasar sains

Loss of the integrin-activating transmembrane protein Fam38A (Piezo1) promotes a switch to a reduced integrin-dependent mode of cell migration

Lung cancer is one of the most common fatal diseases in the developed world. The disease is rarely cured by currently available therapies, with an overall survival rate of ∼10%. Characterizing novel proteins that offer crucial insights into the processes of lung tumour invasion and metastasis may therefore provide much-needed prognostic markers, and influence therapeutic strategies. Aberrant function of the integrin family of heterodimeric cell surface receptors is a common theme in cancer--investigation into novel integrin activity regulators may offer crucial insights into the processes of tumour invasion and metastasis and may reveal insights into potential therapeutic targets. We previously described that depletion of the novel multi-transmembrane domain protein Fam38A, located at the endoplasmic reticulum (ER), inactivates endogenous beta1 integrin affinity, reducing cell adhesion. We now show that depletion of Fam38A, also now known as Piezo1, causes anchorage independence and a switch to a reduced integrin-dependent mode of cell migration/invasion, a novel phenotype for this integrin-regulating protein. Normal lung epithelial cells show increased rates of migration by 2D time-lapse microscopy and increased capacity to invade into matrigel, despite having decreased integrin affinity. We confirm greatly depleted Fam38A expression in small cell lung cancer (SCLC) lines where a form of reduced integrin-dependent migration, i.e. amoeboid migration, is a known phenotype. We propose that loss of Fam38A expression may cause increased cell migration and metastasis in lung tumours

The use of the Nintendo Wii in motor rehabilitation for virtual reality interventions:a literature review

Several review articles have been published on the use of Virtual Reality (VR) in motor rehabilitation. The majority of these focus on the effectiveness of VR on improving motor function using relatively expensive commercial tools and technologies including robotics, cybergloves, cybergrasps, joysticks, force sensors and motion capture systems. However, we present the case in this chapter that game sensors and VR technologies which can be customized and reconfigured, such as the Nintendo Wii, provide an alternative and affordable VR intervention for rehabilitation. While the performance of many of the Wii based interventions in motor rehabilitation are currently the focus of investigation by researchers, an extensive and holistic discussion on this subject does not yet exist. As such, the purpose of this chapter is to provide readers with an understanding of the advantages and limitations of the Nintendo Wii game sensor device (and its associated accessories) for motor rehabilitation and in addition, to outline the potential for incorporating these into clinical interventions for the benefit of patients and therapists

Two family interventions to reduce BMI in low-income urban youth: A randomized trial

BACKGROUND: Our primary aim was to evaluate the effects of 2 family-based obesity management interventions compared with a control group on BMI in low-income adolescents with overweight or obesity. METHODS: In this randomized clinical trial, 360 urban-residing youth and a parent were randomly assigned to 1 of 2 behaviorally distinct family interventions or an education-only control group. Eligible children were entering the sixth grade with a BMI $85th percentile. Interventions were 3 years in length; data were collected annually for 3 years. Effects of the interventions on BMI slope (primary outcome) over 3 years and a set of secondary outcomes were assessed. RESULTS: Participants were primarily African American (77%), had a family income of,25 000 per year, and obese at enrollment (68%). BMI increased over time in all study groups, with group increases ranging from 0.95 to 1.08. In an intent-to-treat analysis, no significant differences were found in adjusted BMI slopes between either of the family-based interventions and the control group (P = .35). No differences were found between the experimental and control groups on secondary outcomes of diet, physical activity, sleep, perceived stress, or cardiometabolic factors. No evidence of effect modification of the study arms by sex, race and/or ethnicity, household income, baseline levels of child and parent obesity, or exposure to a school fitness program were found. CONCLUSIONS: In this low-income, adolescent population, neither of the family-based interventions improved BMI or health-related secondary outcomes. Future interventions should more fully address poverty and other social issues contributing to childhood obesity

PET imaging of αvβ3 integrin expression in tumours with 68Ga-labelled mono-, di- and tetrameric RGD peptides

Contains fulltext : 97195.pdf (publisher's version ) (Closed access)PURPOSE: Due to the restricted expression of alpha(v)beta(3) in tumours, alpha(v)beta(3) is considered a suitable receptor for tumour targeting. In this study the alpha(v)beta(3)-binding characteristics of (68)Ga-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared with their (111)In-labelled counterparts. METHODS: A monomeric (E-c(RGDfK)), a dimeric (E-[c(RGDfK)](2)) and a tetrameric (E{E[c(RGDfK)](2)}(2)) RGD peptide were synthesised, conjugated with DOTA and radiolabelled with (68)Ga. In vitro alpha(v)beta(3)-binding characteristics were determined in a competitive binding assay. In vivo alpha(v)beta(3)-targeting characteristics of the compounds were assessed in mice with subcutaneously growing SK-RC-52 xenografts. In addition, microPET images were acquired using a microPET/CT scanner. RESULTS: The IC(50) values for the Ga(III)-labelled DOTA-E-c(RGDfK), DOTA-E-[c(RGDfK)](2) and DOTA-E{E[c(RGDfK)](2)}(2) were 23.9 +/- 1.22, 8.99 +/- 1.20 and 1.74 +/- 1.18 nM, respectively, and were similar to those of the In(III)-labelled mono-, di- and tetrameric RGD peptides (26.6 +/- 1.15, 3.34 +/- 1.16 and 1.80 +/- 1.37 nM, respectively). At 2 h post-injection, tumour uptake of the (68)Ga-labelled mono-, di- and tetrameric RGD peptides (3.30 +/- 0.30, 5.24 +/- 0.27 and 7.11 +/- 0.67%ID/g, respectively) was comparable to that of their (111)In-labelled counterparts (2.70 +/- 0.29, 5.61 +/- 0.85 and 7.32 +/- 2.45%ID/g, respectively). PET scans were in line with the biodistribution data. On all PET scans, the tumour could be clearly visualised. CONCLUSION: The integrin affinity and the tumour uptake followed the order of DOTA-tetramer > DOTA-dimer > DOTA-monomer. The (68)Ga-labelled tetrameric RGD peptide has excellent characteristics for imaging of alpha(v)beta(3) expression with PET