128 research outputs found
Kerker Conditions Upon Lossless, Absorption, and Optical Gain Regimes
The directionality and polarization of light show peculiar properties when
the scattering by a dielectric sphere can be described exclusively by electric
and magnetic dipolar modes. Particularly, when these modes oscillate in-phase
with equal amplitude, at the so-called first Kerker condition, the zero optical
backscattering condition emerges for non-dissipating spheres. However, the role
of absorption and optical gain in the first Kerker condition remains
unexplored. In this work, we demonstrate that either absorption or optical gain
precludes the first Kerker condition and, hence, the absence of backscattered
radiation light, regardless of the size of the particle, incident wavelength,
and incoming polarization. Finally, we derive the necessary prerequisites of
the second Kerker condition of the zero forward light scattering, finding that
optical gain is a compulsory requirement
CSF1R blockade slows the progression of amyotrophic lateral sclerosis by reducing microgliosis and invasion of macrophages into peripheral nerves
Inflammation is a common neuropathological feature in several neurological disorders, including amyotrophic lateral sclerosis (ALS). We have studied the contribution of CSF1R signalling to inflammation in ALS, as a pathway previously reported to control the expansion and activation of microglial cells. We found that microglial cell proliferation in the spinal cord of SOD1G93A transgenic mice correlates with the expression of CSF1R and its ligand CSF1. Administration of GW2580, a selective CSF1R inhibitor, reduced microglial cell proliferation in SOD1G93A mice, indicating the importance of CSF1-CSF1R signalling in microgliosis in ALS. Moreover, GW2580 treatment slowed disease progression, attenuated motoneuron cell death and extended survival of SOD1G93A mice. Electrophysiological assessment revealed that GW2580 treatment protected skeletal muscle from denervation prior to its effects on microglial cells. We found that macrophages invaded the peripheral nerve of ALS mice before CSF1R-induced microgliosis occurred. Interestingly, treatment with GW2580 attenuated the influx of macrophages into the nerve, which was partly caused by the monocytopenia induced by CSF1R inhibition. Overall, our findings provide evidence that CSF1R signalling regulates inflammation in the central and peripheral nervous system in ALS, supporting therapeutic targeting of CSF1R in this disease
Association of aromatase and estrogen receptor gene polymorphisms with hip fractures
Producción CientíficaSummary Two polymorphisms of the aromatase and estrogen
receptor genes appeared to interact to influence the risk of
hip fractures in women.
Introduction Allelic variants of the aromatase gene have
been associated with bone mineral density and vertebral
fractures. Our objective was to analyze the relationship
between two polymorphisms of the aromatase and estrogen
receptor genes and hip fracture
El correo electrónico en la consulta de Parkinson: ¿soluciones a un clic? // Use of e-mail for Parkinson's disease consultations: Are answers just a clic away?
INTRODUCCION: La problemática de los trastornos del movimiento (TM) es compleja y la duración y frecuencia de las consultas presenciales puede estar limitada por problemas de espacio y tiempo. Analizamos el funcionamiento de un servicio de atención por correo electrónico institucional para médicos de Atención Primaria (MAP) y pacientes en la Unidad de Trastornos del Movimiento (UTM).
METODOS: Se revisaron retrospectivamente los correos electrónicos enviados y recibidos en un periodo de 4 meses, un año tras su implantación. La dirección se proporcionaba en consulta y mediante sesiones informativas a los MAP del área. Se analizaron datos clínicos y demográficos de los pacientes, tipo de interlocutor, número de consultas, motivo y actuaciones derivadas de ellas.
RESULTADOS: Del 1 de enero al 30 de abril de 2015 se recibieron 137 correos de 63 pacientes (43% varones; edad 71 ± 10,5 años) diagnosticados de enfermedad de Parkinson (76%), parkinsonismos atípicos (10%) y otros (14%), y se enviaron 116 respuestas. En 20 casos (32%) fueron redactados por el paciente, en 38 (60%) por sus familiares y en 5 (8%) por MAP. Los motivos de consulta fueron clínicos en 50 casos (80%): deterioro clínico (16; 32%), nuevos síntomas (14; 28%), efectos secundarios o dudas sobre medicación (20; 40%). Como consecuencia, se adelantó una cita programada en 9 casos (14%), mientras que el resto se solucionaron por correo electrónico. En 13 (20%), el motivo de consulta fue burocrático: relacionado con citas (11, 85%) y solicitud de informe (2, 15%). La satisfacción fue generalizada, sin constituir una sobrecarga asistencial excesiva para los facultativos responsables.
CONCLUSIONES: La implantación de una consulta por correo electrónico es factible en UTM, facilita la comunicación médico-paciente y la continuidad asistencial con Atención Primaria. //
INTRODUCTION: The clinical problems of patients with movement disorders (MD) are complex, and the duration and frequency of face-to-face consultations may be insufficient to meet their needs. We analysed the implementation of an e-mail-based query service for our MD unit's patients and their primary care physicians (PCPs).
METHODS: We retrospectively reviewed all consecutive emails sent and received over a period of 4 months, one year after implementation of the e-mail inquiry system. All patients received the during consultations, and PCPs, during scheduled informative meetings. We recorded and later analysed the profile of the questioner, patients’ demographic and clinical data, number of queries, reason for consultation, and actions taken.
RESULTS: From 1 January 2015 to 30 April 2015, the service received 137 emails from 63 patients (43% male, mean age 71 ± 10.5) diagnosed with Parkinson's disease (76%), atypical parkinsonism (10%), and others (14%); 116 responses were sent. Twenty (32%) emails were written by patients, 38 (60%) by their caregivers, and 5 (8%) by their PCPs. The reasons for consultation were clinical in 50 cases (80%): 16 (32%) described clinical deterioration, 14 (28%) onset of new symptoms, and 20 (40%) side effects or concerns about medications. In 13 cases (20%), the query was bureaucratic: 11 were related to appointments (85%) and 2 were requests for clinical reports (15%). In response, new appointments were scheduled in 9 cases (14%), while the rest of the questions were answered by email. Patients were satisfied overall and the additional care burden on specialists was not excessive.
CONCLUSIONS: Implementing an e-mail-based consultation system is feasible in MD units. It facilitates both communication between neurologists and patients and continued care in the primary care setting
CSF1R blockade slows the progression of amyotrophic lateral sclerosis by reducing microgliosis and invasion of macrophages into peripheral nerves
Inflammation is a common neuropathological feature in several neurological disorders, including amyotrophic lateral sclerosis (ALS). We have studied the contribution of CSF1R signalling to inflammation in ALS, as a pathway previously reported to control the expansion and activation of microglial cells. We found that microglial cell proliferation in the spinal cord of SOD1G93A transgenic mice correlates with the expression of CSF1R and its ligand CSF1. Administration of GW2580, a selective CSF1R inhibitor, reduced microglial cell proliferation in SOD1G93A mice, indicating the importance of CSF1-CSF1R signalling in microgliosis in ALS. Moreover, GW2580 treatment slowed disease progression, attenuated motoneuron cell death and extended survival of SOD1G93A mice. Electrophysiological assessment revealed that GW2580 treatment protected skeletal muscle from denervation prior to its effects on microglial cells. We found that macrophages invaded the peripheral nerve of ALS mice before CSF1R-induced microgliosis occurred. Interestingly, treatment with GW2580 attenuated the influx of macrophages into the nerve, which was partly caused by the monocytopenia induced by CSF1R inhibition. Overall, our findings provide evidence that CSF1R signalling regulates inflammation in the central and peripheral nervous system in ALS, supporting therapeutic targeting of CSF1R in this disease
Serum 25-hydroxyvitamin D, parathyroid hormone, calcium intake, and bone mineral density in Spanish adults
Summary Vitamin D insufficiency is very common among Spanish community-dwelling adult subjects. A threshold of serum 25(OH)D around 30 ng/ml would be necessary for the prevention of secondary hyperparathyroidism and hip bone loss in our population, regardless of the dairy calcium ingestion. Introduction This study aims to assess 25-hydroxyvitamin D?25(OH)D?status in Spanish adult subjects and to analyze its relationships with serum PTH levels, calcium intake, and bone mineral density (BMD). Methods A total of 1811 individuals (1154 postmenopausal women and 657 men) aged 44?93 years participated in the study. Serum 25(OH)D, intact parathyroid hormone (PTH), aminoterminal propeptide of type I collagen (P1NP), and Cterminal telopeptide of type I collagen (?-CTX) levels were measured by electrochemiluminescence. BMD was determined by dual x-ray absorptiometry (DXA) at lumbar spine, femoral neck, and total hip. Results Serum 25(OH)D levels were below 10, 20, and 30 ng/ml in 5, 40, and 83%of participants, respectively. There was a significant seasonal difference in mean serum 25(OH)D, with higher levels in summer?autumn. In multivariate analysis, 25(OH)D levels were negatively correlated with age, serum PTH and creatinine, body mass index, smoking, alcohol intake, and a number of chronic diseases, but positively with dairy calcium intake. The magnitude of the difference in serum PTH according to 25(OH)D quartiles was not influenced by calcium intake. A threshold of serum 25(OH)D around 30 ng/ml was observed for serum PTH and hip BMD. Conclusions Vitamin D insufficiency is very common among Spanish community-dwelling adult subjects. A threshold of serum 25(OH)D around 30 ng/ml would be necessary for the prevention of secondary hyperparathyroidism and hip bone loss in our population, regardless of the dairy calcium ingestion. Programs to improve vitamin D status may be required in our country
Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density.
OBJECTIVES: To identify genetic determinants of susceptibility to clinical vertebral fractures, which is an important complication of osteoporosis. METHODS: Here we conduct a genome-wide association study in 1553 postmenopausal women with clinical vertebral fractures and 4340 controls, with a two-stage replication involving 1028 cases and 3762 controls. Potentially causal variants were identified using expression quantitative trait loci (eQTL) data from transiliac bone biopsies and bioinformatic studies. RESULTS: A locus tagged by rs10190845 was identified on chromosome 2q13, which was significantly associated with clinical vertebral fracture (P=1.04×10-9) with a large effect size (OR 1.74, 95% CI 1.06 to 2.6). Bioinformatic analysis of this locus identified several potentially functional SNPs that are associated with expression of the positional candidate genes TTL (tubulin tyrosine ligase) and SLC20A1 (solute carrier family 20 member 1). Three other suggestive loci were identified on chromosomes 1p31, 11q12 and 15q11. All these loci were novel and had not previously been associated with bone mineral density or clinical fractures. CONCLUSION: We have identified a novel genetic variant that is associated with clinical vertebral fractures by mechanisms that are independent of BMD. Further studies are now in progress to validate this association and evaluate the underlying mechanism
Known and unknown requirements in healthcare
We report experience in requirements elicitation of domain knowledge from experts in clinical and cognitive neurosciences. The elicitation target was a causal model for early signs of dementia indicated by changes in user behaviour and errors apparent in logs of computer activity. A Delphi-style process consisting of workshops with experts followed by a questionnaire was adopted. The paper describes how the elicitation process had to be adapted to deal with problems encountered in terminology and limited consensus among the experts. In spite of the difficulties encountered, a partial causal model of user behavioural pathologies and errors was elicited. This informed requirements for configuring data- and text-mining tools to search for the specific data patterns. Lessons learned for elicitation from experts are presented, and the implications for requirements are discussed as “unknown unknowns”, as well as configuration requirements for directing data-/text-mining tools towards refining awareness requirements in healthcare applications
Assessment of gene-by-sex interaction effect on bone mineral density
To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p < 1 × 10(-5) ) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect = 0.02 and p = 3.0 × 10(-5) ; female effect = -0.007 and p = 3.3 × 10(-2) ), and 11 suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (p < 5 × 10(-8) ) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found to influence BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP. © 2012 American Society for Bone and Mineral Research.Medtronic
NIH R01 AG18728
R01HL088119
R01AR046838
U01 HL084756
R01 AR43351
P01-HL45522
R01-MH-078111
R01-MH-083824
Nutrition and Obesity Research Center of Maryland P30DK072488
NIAMS/NIH F32AR059469
Instituto de Salud Carlos III-FIS (Spanish Health Ministry) PI 06/0034
PI08/0183
Canadian Institutes of Health Research (CIHR)
NHLBI HHSN268201200036C
N01-HC-85239
N01-HC-85079
N01-HC-85086
N01-HC-35129
N01 HC15103
N01 HC-55222
N01-HC-75150
N01-HC-45133
HL080295
HL087652
HL105756
NIA AG-023629
AG-15928
AG-20098
AG-027058
N01AG62101
N01AG62103
N01AG62106
1R01AG032098-01A1
National Center of Advancing Translational Technologies CTSI UL1TR000124
National Institute of Diabetes and Digestive and Kidney Diseases DK063491
EUROSPAN (European Special Populations Research Network)
European Commission FP6 STRP grant 018947
LSHG-CT-2006-01947
Netherlands Organisation for Scientific Research
Erasmus MC
Centre for Medical Systems Biology (CMSB)
Netherlands Brain Foundation (HersenStichting Nederland)
US National Institute for Arthritis, Musculoskeletal and Skin Diseases
National Institute on Aging R01 AR/AG41398
R01 AR050066
R21 AR056405
National Heart, Lung, and Blood Institute's Framingham Heart Study N01-HC-25195
Affymetrix, Inc. N02-HL-6-4278
Canadian Institutes of Health Research from Institute of Aging 165446
Institute of Genetics 179433
Institute of Musculoskeletal health 221765
Intramural Research Program of the NIH, National Institute on Aging
National Institutes of Health HHSN268200782096C
Hong Kong Research Grant Council HKU 768610M
Bone Health Fund of HKU Foundation
KC Wong Education Foundation
Small Project Funding 201007176237
Matching Grant
CRCG Grant
Osteoporosis and Endocrine Research Fund
Genomics Strategic Research Theme of The University of Hong Kong
Netherlands Organisation of Scientific Research NWO Investments 175.010.2005.011
911-03-012
Research Institute for Diseases in the Elderly 014-93-015
Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) 050-060-810
Erasmus Medical Center and Erasmus University, Rotterdam
Netherlands Organization for the Health Research and Development (ZonMw)
Research Institute for Diseases in the Elderly (RIDE)
Ministry of Education, Culture and Science
Ministry for Health, Welfare and Sports
European Commission (DG XII)
Municipality of Rotterdam
German Bundesministerium fur Forschung und Technology 01 AK 803 A-H
01 IG 07015
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