Autoantibody Profiling of Glioma Serum Samples to Identify Biomarkers Using Human Proteome Arrays

The heterogeneity and poor prognosis associated with gliomas, makes biomarker identification imperative. Here, we report autoantibody signatures across various grades of glioma serum samples and sub-categories of glioblastoma multiforme using Human Proteome chips containing similar to 17000 fulllength human proteins. The deduced sets of classifier proteins helped to distinguish Grade II, III and IV samples from the healthy subjects with 88, 89 and 94% sensitivity and 87, 100 and 73% specificity, respectively. Proteins namely, SNX1, EYA1, PQBP1 and IGHG1 showed dysregulation across various grades. Sub-classes of GBM, based on its proximity to the sub-ventricular zone, have been reported to have different prognostic outcomes. To this end, we identified dysregulation of NEDD9, a protein involved in cell migration, with probable prognostic potential. Another subcategory of patients where the IDH1 gene is mutated, are known to have better prognosis as compared to patients carrying the wild type gene. On a comparison of these two cohorts, we found STUB1 and YWHAH proteins dysregulated in Grade II glioma patients. In addition to common pathways associated with tumourigenesis, we found enrichment of immunoregulatory and cytoskeletal remodelling pathways, emphasizing the need to explore biochemical alterations arising due to autoimmune responses in glioma

Bladder cancer and reproductive factors among women in Spain

Hormonal factors, possibly related to reproductive characteristics, may play a role in the risk of bladder cancer among women. To study this, we investigated the effects of reproductive factors on female bladder cancer risk. Information on reproductive and other risk factors was gathered in personal interviews from 152 female cases and 166 matched controls from 18 hospitals in five regions of Spain during 1998–2001. Logistic regression was used to estimate the association between bladder cancer and reproductive factors, including ever-parous status, age at first live birth, age at last live birth, age at menarche, age at menopause, menopausal status, and duration of menstruation. After adjustment for age, smoking, and high-risk occupation, ever-parous women were at decreased risk relative to nulliparous women (odds ratio = 0.43, 95% confidence interval = 0.21–0.87). There was no consistent pattern in risk with the age- or duration-related reproductive factors (e.g., age at first live birth, age at last live birth, age at menarche, age at menopause, menopausal status, and duration of menstruation) that we evaluated. Women have a lower risk of bladder cancer than men, and hormonal factors related to childbearing may play a role

Postural stability deficit could predict ankle sprains: a systematic review

Purpose: To perform a systematic review aimed to determine (1) if the postural stability deficit represents a risk factor for ankle sprains; (2) the most effective postural stability evaluation to predict ankle sprains and (3) eventual confounding factors that could influence postural stability and ankle sprain risk. Methods: A systematic electronic search was performed in MEDLINE, EMBASE and CINAHL using the search terms (balance) OR (postural stability) matched with (lower limb) OR (ankle) OR (foot) and (sprain) OR (injury) on October 2 2017. All prospective studies that evaluated postural stability as risk factor for ankle sprains were included. The PRISMA Checklist guided the reporting and data abstraction. Methodological quality of all included papers was carefully assessed. Results: Fifteen studies were included, evaluating 2860 individuals. Various assessment tools or instruments were used to assess postural stability. The injury incidence ranged from 10 to 34%. Postural stability deficit was recognized as risk factor for ankle sprain (OR = 1.22\ue2\u80\u9310.2) in 9 cases [3 out of 3 with Star Excursion Balance Test (SEBT)]. Among the six studies that measured the center-of-gravity sway, five were able to detect worse postural stability in athletes that sustained an ankle sprain. In nine cases, the measurement of postural stability did not show any statistical relationship with ankle sprains (four out of five with examiner evaluation). In the studies that excluded patients with history of ankle sprain, postural stability was reported to be a significant risk factor in five out of six studies. Conclusions: The ultimate role of postural stability as risk factor for ankle sprains was not defined, due to the high heterogeneity of results, patient\ue2\u80\u99s populations, sports and methods of postural stability evaluation. Regarding assessment instruments, measurement of center-of-gravity sway could detect athletes at risk, however, standardized tools and protocols are needed to confirm this finding. The SEBT could be considered a promising tool that needs further investigation in wider samples. History of ankle sprains is an important confounding factor, since it was itself a source of postural stability impairment and a risk factor for ankle sprains. These information could guide clinicians in developing screening programs and design further prospective cohort studies comparing different evaluation tools. Level of evidence: I (systematic review of prospective prognostic studies)

Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis

We have analysed data on exacerbation rates, Expanded Disability Status Scale (EDSS) scores, and lesion burdens using the results of two neutralizing antibody (NAB) assays (CPE and MxA) from the pivotal relapsing-remitting multiple sclerosis (MS) trial of interferon beta-1b (IFNB) with a longitudinal approach, where the influence of NABs in individual patients is assessed by comparing responses during NAB-positive and NAB-negative periods. There are apparent influences on exacerbation rate related to dose of IFNB, titer level, and duration of positivity. With the MxA assay, exacerbation rates after switching to NAB-positive status are estimated to be 28% higher [95% confidence interval (CI): (-15%, 92%)] and -2% higher [95% CI: (-21%, 21%)] on the low- and high-dose IFNB arms, respectively. When compared with all NAB-negative periods, exacerbation rates during NAB-positive periods are estimated to be 29% higher [95% CI: (0%, 67%)] and 18% higher [95% CI: (0%, 40%)] on the low- and high-dose IFNB arms, respectively. When NAB-positive patients again become NAB-negative, no evidence of increased exacerbation rates could then be demonstrated. More detailed exploratory analyses indicate that the effects are most evident in the approximately 20% of patients developing high titers. In these patients, the influence of NABs may be self-limited, as titers often diminish or NABs become undetectable with time. © Arnold 2004