C5

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Complement C5 precursor (C3 and PZP-like alpha-2-macroglobulin domain-containing protein 4) [Contains: Complement C5 beta chain; Complement C5 alpha chain; C5a anaphylatoxin; Complement C5 alpha' chain] [CPAMD4]

Publications[править]

The C5-75 Program: Meeting the Need for Efficient, Pragmatic Frailty Screening and Management in Primary Care.

Case-Finding for Complex Chronic Conditions in Seniors 75 (C5-75) is a systematic approach to identify frailty using gait speed and hand-grip strength and to screen for co-morbid conditions. We identified the C5-75 features offering the highest yield for identifying frailty and to streamline the screening program. Analyses included 1,948 C5-75 assessments completed from 2013 to 2018. Age 85 or older, less than regular physical activity, and more than two falls in the previous six months had the strongest associations with frailty. Exempting patients under 85 who reported regular physical activity and less than two falls excluded 39.1 per cent of the cohort while maintaining a sensitivity of 95.2 per cent and a negative predictive value of 99.4 per cent for frailty. These findings provide insight into optimizing screening for frailty, making it more feasible to implement and to identify co-existing conditions that may contribute to or be affected by frailty.


Keywords

  • aging
  • case-finding
  • co-morbid conditions
  • comorbidité
  • dépistage
  • fragilité
  • frailty
  • primary care
  • recherche de cas
  • screening
  • soins de première ligne
  • vieillissement


Can a relatively large spinal cord for the dural sac influence severity of paralysis in elderly patients with cervical spinal cord injury caused by minor trauma?

Retrospective reviewThe degree of spinal cord compression and bony spinal canal stenosis are risk factors for the occurrence of spinal cord injury (SCI) without major fracture or dislocation, but they do not affect the severity of neurological symptoms. However, whether a relatively large spinal cord for the dural sac influences the severity of symptoms in SCI cases is unknown.The purpose of this study was to verify the influence of spinal cord size relative to dural sac on the severity of paralysis in elderly patients with cervical SCI caused by minor trauma.Subjects were 50 elderly patients with SCI caused by falls on flat ground. At 72 hours after injury, neurological assessment was performed using the Japanese Orthopaedic Association (JOA) scoring system. Bony canal anteroposterior diameters (APD) at mid C5 vertebral body were measured with computed tomography. We measured dural sac and spinal cord APD at the injured level and mid C5 with magnetic resonance imaging. Spinal cord compression ratio was calculated by dividing spinal cord at the injured level by spinal cord at mid C5. As the evaluation of spinal cord size relative to the dural sac, spinal cord/dural sac ratio was calculated at the injured level and mid C5. To clarify the factors influencing the severity of paralysis, the relationships between JOA score and those parameters were examined statistically.A significant negative correlation was observed between JOA score and spinal cord/dural sac ratio at mid C5. No clear relationship was observed between JOA score and bony canal APD or spinal cord compression ratio.In elderly patients with SCI caused by minor trauma, a relatively large spinal cord for the dural sac was shown to be a factor that influences the severity of paralysis. This result can be useful for the treatment and prevention of SCI in the elderly.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Cervical Vertebrae
  • Female
  • Geriatrics
  • Humans
  • Japan
  • Magnetic Resonance Imaging
  • Male
  • Paralysis
  • Severity of Illness Index
  • Spinal Canal
  • Spinal Cord
  • Spinal Cord Injuries
  • Tomography, X-Ray Computed
  • Wounds and Injuries


Age and Sex-Associated Changes of Complement Activity and Complement Levels in a Healthy Caucasian Population.

The complement system is essential for an adequate immune response. Much attention has been given to the role of complement in disease. However, to better understand complement in pathology, it is crucial to first analyze this system under different physiological conditions. The aim of the present study was therefore to investigate the inter-individual variation in complement activity and the influences of age and sex. Complement levels and functional activity were determined in 120 healthy volunteers, 60 women, 60 men, age range 20-69 year. Serum functional activity of the classical pathway (CP), lectin pathway activated by mannan (MBL-LP) and alternative pathway (AP) was measured in sera, using deposition of C5b-9 as readout. In addition, levels of C1q, MBL, MASP-1, MASP-2, ficolin-2, ficolin-3, C2, C4, C3, C5, C6, C7, C8, C9, factor B, factor D, properdin, C1-inhibitor and C4b-binding protein, were determined. Age- and sex-related differences were evaluated. Significantly lower AP activity was found in females compared to males. Further analysis of the AP revealed lower C3 and properdin levels in females, while factor D concentrations were higher. MBL-LP activity was not influenced by sex, but MBL and ficolin-3 levels were significantly lower in females compared to males. There were no significant differences in CP activity or CP components between females and males, nevertheless females had significantly lower levels of the terminal components. The CP and AP activity was significantly higher in the elderly, in contrast to MBL-LP activity. Moreover, C1-inhibitor, C5, C8, and C9 increased with age in contrast to a decrease of factor D and C3 levels. In-depth analysis of the functional activity assays revealed that MBL-LP activity was predominantly dependent on MBL and MASP-2 concentration, whereas CP activity relied on C2, C1-inhibitor and C5 levels. AP activity was strongly and directly associated with levels of C3, factor B and C5. This study demonstrated significant sex and age-related differences in complement levels and functionality in the healthy population. Therefore, age and sex analysis should be taken into consideration when discussing complement-related pathologies and subsequent complement-targeted therapies.

MeSH Terms

  • Adult
  • Aged
  • Aging
  • Complement Activation
  • Complement System Proteins
  • European Continental Ancestry Group
  • Female
  • Humans
  • Male
  • Middle Aged
  • Sex Characteristics

Keywords

  • complement
  • gender
  • health
  • innate imunity
  • sex and age


Longevity of adenovirus vector immunity in mice and its implications for vaccine efficacy.

There is a high incidence of adenovirus (AdV) infection in humans due to the presence of more than 60 types of human adenoviruses (HAdVs). The majority of individuals are exposed to one or more HAdV types early in their lives, leading to the development of AdV type-specific neutralizing antibodies. Similarly, immunization or gene therapy with AdV vectors leads to immune responses to the AdV vector. This 'vector immunity' is a concern for AdV vector-based applications for vaccines or gene therapy, especially when the repeated administration of a vector is required. The objective of this investigation was to establish whether AdV neutralizing antibody titers decline sufficiently in a year to permit annual vaccination with the same AdV vector. Naïve or human adenoviral vector group C, type 5 (HAdV-C5)-primed mice were mock-inoculated (with PBS) or inoculated i.m. with 10  PFU of either HAd-GFP [HAdV-C5 vector expressing the green fluorescent protein (GFP)] to mimic the conditions for the first inoculation with an AdV vector-based vaccine. At 1, 3, 6, and 10 months post-HAd-GFP inoculation, naïve- or HAdV-primed animals were vaccinated i.m. with 10  PFU of HAd-H5HA [HAdV-C5 vector expressing hemagglutinin (HA) of H5N1 influenza virus]. There was a significant continual decrease in vector immunity titers with time, thereby leading to significant continual increases in the levels of HA-specific humoral and cell-mediated immune responses. In addition, significant improvement in protection efficacy against challenge with an antigenically heterologous H5N1 virus was observed in HAdV-primed animals at 6 months and onwards. These results indicate that the annual immunization with the same AdV vector may be effective due to a significant decline in vector immunity.

MeSH Terms

  • Adenoviridae
  • Animals
  • Antibodies, Neutralizing
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genetic Vectors
  • Influenza A Virus, H5N1 Subtype
  • Influenza Vaccines
  • Mice
  • Mice, Inbred BALB C

Keywords

  • Adenoviral vectors
  • Avian influenza
  • Human adenoviral vector
  • Longevity of adenoviral vector immunity
  • Prevalence of vector immunity
  • Vector immunity


Generating Rasch-based activity of daily living measures from the Spinal Cord Injury Longitudinal Aging Study.

Retrospective Longitudinal Study. (1) To determine whether the Spinal Cord Injury Activities of Daily Living (SCI_ADL) measure shows adequate item-level and precision psychometrics; (2) to investigate whether the SCI_ADL measure effectively detects ADL changes across time; (3) to describe self-care task(s) participants can and cannot do across time. Two Midwestern hospitals and 1 Southeastern specialty hospital in 1993. All participants were adults with traumatic SCI of at least 1-year duration at enrollment. We used 20-year (1993-2013) retrospective longitudinal data and categorized participants into three injury levels: C1-C4 (cervical; n=50), C5-C8 (n=126) and T1-S5 (thoracic, lumbar and sacral; n=168). We first examined psychometrics of the SCI_ADL with factor and Rasch analyses; then we investigated longitudinal change of SCI_ADL scores at three time points over 20 years (1993, 2003 and 2013) using generalized linear mixed modeling and post hoc analyses. The SCI_ADL measure demonstrated unidimensionality, person strata of 2.9, high Cronbach's α (0.93) and fair person reliability (0.76). T1-S5 had the highest measures, following C5-C8 and C1-C4 at three time points (P<0.05). The C1-C4 and T1-S5 groups showed significant decreases from 2003 to 2013; however, none of the three groups showed significant differences from 1993 to 2003 (P<0.05). The SCI_ADL measure could detect longitudinal ADL changes of the population with SCI across time. The C1-C4 group decreased the most in ADLs, indicating higher need of long-term services and rehabilitation.

MeSH Terms

  • Activities of Daily Living
  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aging
  • Cohort Studies
  • Disability Evaluation
  • Female
  • Humans
  • Male
  • Middle Aged
  • Principal Component Analysis
  • Psychometrics
  • Spinal Cord Injuries
  • Young Adult


A Large Cohort Study of 18F Fluoro-Deoxy-Glucose Uptake in Normal Spinal Cord: Quantitative Assessment of the Contamination From Adjacent Vertebral Marrow Uptake and Validity of Normalizing the Cord Uptake Against the Lumbar Thecal Sac.

This study aimed (1) to assess the influence of age, sex, blood glucose, and body mass index on the F fluoro-deoxy-glucose (F-FDG) uptake in normal spinal cord; (2) to quantitatively evaluate contamination of the spinal cord SUVmax by the adjacent vertebral marrow activity; and (3) to investigate the validity of normalizing spinal cord SUVmax against lumbar thecal sac SUVmax. Two hundred positron emission tomography-computed tomography examinations of subjects with normal spinal cord were retrospectively reviewed. SUVmax of spinal cord and vertebral body was obtained at C2, C5, T6, T12, and L3 levels. Pearson correlation coefficients (r) were obtained at each level between spinal cord SUVmax and vertebral marrow SUVmax, age, body mass index, and blood glucose. Cord to background ratio (CTB) was calculated as the ratio between SUVmax of spinal cord and SUVmax of L3 thecal sac. The coefficient of variation (CV) of spinal cord SUVmax was compared with the CV of CTB. Spinal cord SUVmax was highest at C2 (mean, 1.76) and lowest at T6 (mean, 1.37) with SD of 0.32 to 0.36 SUV. Sex (P > 0.45), age (r: -0.25 to -0.06), body mass index (r: 0.19 to 0.27), and blood glucose (r: -0.17 to 0.22) had no impact on the spinal cord SUVmax. A moderate to strong positive correlation (r: 0.66-0.80) was found between spinal cord SUVmax and the corresponding vertebral marrow SUVmax. The CV of CTB was greater (0.28-0.32) than the CV of spinal cord SUVmax (0.19-0.25) across all levels. Of the variables studied, only contamination from adjacent vertebral marrow activity significantly affected the SUVmax of spinal cord. This contamination should be corrected for when reporting spinal cord FDG uptake. Lumbar thecal sac is not a valid reference for normalizing spinal cord FDG uptake.

MeSH Terms

  • Age Distribution
  • Aging
  • Bone Marrow
  • Cohort Studies
  • Dura Mater
  • Female
  • Florida
  • Fluorodeoxyglucose F18
  • Humans
  • Image Interpretation, Computer-Assisted
  • Lumbar Vertebrae
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Radiopharmaceuticals
  • Reference Values
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sex Distribution
  • Spinal Cord


Demographic aspects in cervical vertebral bodies' size and shape (C3-C7): a skeletal study.

This cross-sectional study was conducted on the skeletal remains of individuals of known sex, age, and ethnic origin. The vertebral bodies of levels C3-C7 were measured and analyzed. Whereas many studies were performed on the size and shape of the vertebral bodies in the thoracic and lumbar spines, few have focused on the cervical vertebral bodies. Thus, there is insufficient data in the literature on the anatomy of the cervical spine, especially based on large study populations. To establish a large database on cervical vertebral bodies' size and shape and analyze their association with demographic parameters. The population studied was composed of 277 individuals, adult males and females of African American (AA) and European American (EA) origin. The skeletal remains are housed at the Hamman-Todd Osteological collection (Cleveland Museum of Natural History, Cleveland, OH). A 3-D digitizer was used to measure the size and shape of the C3-C7 vertebral bodies. Descriptive statistics were carried out for all measurements. t Test and one-way analysis of variance were performed to assess differences in vertebral bodies' size and shape between different demographical groups (by age, sex, and ethnicity). The vertebral bodies and foramina are significantly wider, more elongated, and higher in males compared to females. AA females and males manifest significantly greater vertebral bodies (width and length) in the upper and midcervical region (vertebrae C3-C5) than EA females and males. Nevertheless, the heights of the C3 and C4 vertebral bodies are significantly smaller among the AA population, regardless of sex. The vertebral foramina's width does not differ significantly between the two ethnic groups, independent of sex, whereas they tend to be elongated in the EA group (significant for C3, C5, C7). For most vertebrae, no significant differences were found in the superior facets' length between AA and EA males and females. Cervical vertebral bodies become wider and more elongated with age, although the changes in the latter dimension are much more pronounced than in the former. Notably, the body shape of the cervical vertebrae changes gradually from a more round shape (C3 length/width index=0.84) to a more oval one (C7 length/width index =0.65). This is due to the fact that the width dimensions increase by almost 40% from C3 to C7, whereas the length dimensions increase only by approximately 10%. Furthermore, there is a significant reduction in body height with age in C3-C6. In contrast, no significant changes in vertebral foramen size with age were found. The cervical vertebral bodies' shape and size are sex-dependent phenomena, that is, in all parameters studied, the dimensions were greater in males than in females. For the midcervical level, there is a difference in body shape between individuals of different ethnic origins. The cervical vertebral bodies also exhibit considerable size and shape changes with age, that is, they become more elongated (oval shaped), wider, and shorter. In contrast, vertebral foramen size is age independent.

MeSH Terms

  • Adult
  • African Americans
  • Body Height
  • Cervical Vertebrae
  • Cross-Sectional Studies
  • European Continental Ancestry Group
  • Female
  • Humans
  • Lumbar Vertebrae
  • Male
  • Middle Aged
  • Organ Size

Keywords

  • Aging
  • Cervical spine
  • Skeletal study
  • Spinal anatomy
  • Vertebral body
  • Vertebral foramen

{{medline-entry |title=Tract-specific and age-related variations of the spinal cord microstructure: a multi-parametric MRI study using diffusion tensor imaging (DTI) and inhomogeneous magnetization transfer (ihMT). |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27100385 |abstract=Being able to finely characterize the spinal cord (SC) microstructure and its alterations is a key point when investigating neural damage mechanisms encountered in different central nervous system (CNS) pathologies, such as multiple sclerosis, amyotrophic lateral sclerosis or myelopathy. Based on novel methods, including inhomogeneous magnetization transfer (ihMT) and dedicated SC probabilistic atlas post-processing, the present study focuses on the in vivo characterization of the healthy SC tissue in terms of regional microstructure differences between (i) upper and lower cervical vertebral levels and (ii) sensory and motor tracts, as well as differences attributed to normal aging. Forty-eight healthy volunteers aged from 20 to 70 years old were included in the study and scanned at 3 T using axial high-resolution T2 *-w imaging, diffusion tensor imaging (DTI) and ihMT, at two vertebral levels (C2 and C5). A processing pipeline with minimal user intervention, SC segmentation and spatial normalization into a reference space was implemented in order to assess quantitative morphological and structural parameters (cross-sectional areas, scalar DTI and MT/ihMT metrics) in specific white and gray matter regions of interest. The multi-parametric MRI metrics collected allowed upper and lower cervical levels to be distinguished, with higher ihMT ratio (ihMTR), higher axial diffusivity (λ∥ ) and lower radial diffusivity (λ⊥ ) at C2 compared with C5. Significant differences were also observed between white matter fascicles, with higher ihMTR and lower λ∥ in motor tracts compared with posterior sensory tracts. Finally, aging was found to be associated with significant metric alterations (decreased ihMTR and λ∥ ). The methodology proposed here, which can be easily transferred to the clinic, provides new insights for SC characterization. It bears great potential to study focal and diffuse SC damage in neurodegenerative and demyelinating diseases. Copyright © 2016 John Wiley