504 research outputs found

    Age at First Concussion Influences Number of Subsequent Concussions

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    Background: Individuals that sustain their first concussion during childhood may be at greater risk for sustaining multiple concussions throughout their lifetime, due to a longer window of vulnerability. Purpose: To estimate the association between age at first concussion with number of subsequent concussions. Methods: A total of 23,582 collegiate athletes from 26 universities and military cadets from three military academies completed a concussion history questionnaire (65% males, age: 19.9±1.4years). Participants self-reported concussions and age at time of each injury. Participants with a history of concussion (n=3,647, 15.5%) were categorized as having sustained their first concussion during childhood (<10 years old - yo) or adolescence (≥10yo & ≤18yo). Poisson regression was used to model age group (childhood, adolescence) predicting number of subsequent concussions (0, 1, 2+). A second Poisson regression was developed to determine whether age at first concussion predicted number of subsequent concussions. Results: Participants self-reporting their first concussion during childhood had an increased risk of sustaining subsequent concussions (RR=2.19, 95% CI: 1.82, 2.64) compared to participants self-reporting their first concussion during adolescence. For every one-year increase in age at first concussion, we observed a 16% reduction in the risk of subsequent concussion (RR=0.84, 95% CI:0.82,0.86). Conclusion(s): Individuals self-reporting a concussion at a young age sustained a higher number of concussions prior to the age of 18. Concussion prevention, recognition, and reporting strategies are of particular need at the youth level

    Age at First Concussion Influences Number of Subsequent Concussions

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    Background: Individuals that sustain their first concussion during childhood may be at greater risk for sustaining multiple concussions throughout their lifetime, due to a longer window of vulnerability. Purpose: To estimate the association between age at first concussion with number of subsequent concussions. Methods: A total of 23,582 collegiate athletes from 26 universities and military cadets from three military academies completed a concussion history questionnaire (65% males, age: 19.9±1.4years). Participants self-reported concussions and age at time of each injury. Participants with a history of concussion (n=3,647, 15.5%) were categorized as having sustained their first concussion during childhood (<10 years old - yo) or adolescence (≥10yo & ≤18yo). Poisson regression was used to model age group (childhood, adolescence) predicting number of subsequent concussions (0, 1, 2+). A second Poisson regression was developed to determine whether age at first concussion predicted number of subsequent concussions. Results: Participants self-reporting their first concussion during childhood had an increased risk of sustaining subsequent concussions (RR=2.19, 95% CI: 1.82, 2.64) compared to participants self-reporting their first concussion during adolescence. For every one-year increase in age at first concussion, we observed a 16% reduction in the risk of subsequent concussion (RR=0.84, 95% CI:0.82,0.86). Conclusion(s): Individuals self-reporting a concussion at a young age sustained a higher number of concussions prior to the age of 18. Concussion prevention, recognition, and reporting strategies are of particular need at the youth level

    Detection of volatile organic compounds in headspace of Klebsiella pneumoniae and Klebsiella oxytoca colonies

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    Introduction: Early diagnosis of infections and sepsis is essential as adequate therapy improves the outcome. Unfortunately, current diagnostics are invasive and time-consuming, making diagnosis difficult, especially in neonatology. Novel non-invasive analytical methods might be suitable to detect an infection at an early stage and might even allow identification of the pathogen. Our aim is to identify specific profiles of volatile organic compounds (VOCs) of bacterial species. Methods: Using multicapillary column-coupled ion mobility spectrometry (MCC/ IMS), we performed headspace measurements of bacterial cultures from skin and anal swabs of premature infants obtained during weekly screening for bacterial colonization according to KRINKO. We analyzed 25 Klebsiella pneumoniae (KP) cultures on MacConkey (MC) agar plates, 25 Klebsiella oxytoca (KO) cultures on MC agar and 25 bare MC agar plates as a control group. Results: Using MCC/IMS, we identified a total of 159 VOC peaks. 85 peaks allowed discriminating KP and bare MC agar plates, and 51 peaks comparing KO and bare MC agar plates and 6 peaks between KP and KO (significance level of p < 0.05 after Bonferroni post hoc analysis), respectively. Peaks P51 (n-Decane) and P158 (Phenylethyl Alcohol), showed the best sensitivity/specificity/ positive predictive value/negative predictive value of 99.9% each (p < 0.001) for KP. P158 showed the best sensitivity/specificity/positive predictive value/negative predictive value of 99.9% each (p < 0.001) for KO. Comparing KP and KO, best differentiation was enabled using peaks P72, P97 and P16 with sensitivity/specificity/positive predictive value/negative predictive value of 76.0%, 84.0%, 82.6%, 77.8%, respectively (p < 0.05)

    Health related quality of life outcomes following surgery and/or radiation for patients with potentially unstable spinal metastases.

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    Currently there is no prospective pain and health related quality of life (HRQOL) data of patients with potentially unstable spinal metastases who were treated with surgery ± radiation or radiation alone.An international prospective cohort multicenter study of patients with potentially unstable spinal metastases, defined by a SINS score 7 to 12, treated with surgery ± radiation or radiotherapy alone was conducted. HRQOL was evaluated with the numeric rating scale (NRS) pain score, the SOSGOQ2.0, the SF-36, and the EQ-5D at baseline and 6, 12, 26, and 52 weeks after treatment.A total of 136 patients were treated with surgery ± radiotherapy and 84 with radiotherapy alone. At baseline, surgically treated patients were more likely to have mechanical pain, a lytic lesion, a greater median Spinal Instability Neoplastic score, vertebral compression fracture, lower performance status, HRQOL, and pain scores. From baseline to 12 weeks post-treatment, surgically treated patients experienced a 3.0-point decrease in NRS pain score (95% CI -4.1 to -1.9, p.001), and a 12.7-point increase in SOSGOQ2.0 score (95% CI 6.3-19.1, p.001). Patients treated with radiotherapy alone experienced a 1.4-point decrease in the NRS pain score (95% CI -2.9 to 0.0, p=.046) and a 6.2-point increase in SOSGOQ2.0 score (95% CI -2.0 to 14.5, p=.331). Beyond 12 weeks, significant improvements in pain and HRQOL metrics were maintained up to 52-weeks follow-up in the surgical cohort, as compared with no significant changes in the radiotherapy alone cohort.Patients treated with surgery demonstrated clinically and statistically significant improvements in pain and HRQOL up to 1-year postsurgery. Treatment with radiotherapy alone resulted in improved pain scores, but these were not sustained beyond 3 months and HRQOL outcomes demonstrated nonsignificant changes over time. Within the SINS potentially unstable group, distinct clinical profiles were observed in patients treated with surgery or radiotherapy alone

    Detection of volatile organic compounds in headspace of Klebsiella pneumoniae and Klebsiella oxytoca colonies

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    IntroductionEarly diagnosis of infections and sepsis is essential as adequate therapy improves the outcome. Unfortunately, current diagnostics are invasive and time-consuming, making diagnosis difficult, especially in neonatology. Novel non-invasive analytical methods might be suitable to detect an infection at an early stage and might even allow identification of the pathogen. Our aim is to identify specific profiles of volatile organic compounds (VOCs) of bacterial species.MethodsUsing multicapillary column-coupled ion mobility spectrometry (MCC/IMS), we performed headspace measurements of bacterial cultures from skin and anal swabs of premature infants obtained during weekly screening for bacterial colonization according to KRINKO. We analyzed 25 Klebsiella pneumoniae (KP) cultures on MacConkey (MC) agar plates, 25 Klebsiella oxytoca (KO) cultures on MC agar and 25 bare MC agar plates as a control group.ResultsUsing MCC/IMS, we identified a total of 159 VOC peaks. 85 peaks allowed discriminating KP and bare MC agar plates, and 51 peaks comparing KO and bare MC agar plates and 6 peaks between KP and KO (significance level of p &lt; 0.05 after Bonferroni post hoc analysis), respectively. Peaks P51 (n-Decane) and P158 (Phenylethyl Alcohol), showed the best sensitivity/specificity/ positive predictive value/negative predictive value of 99.9% each (p &lt; 0.001) for KP. P158 showed the best sensitivity/specificity/positive predictive value/negative predictive value of 99.9% each (p &lt; 0.001) for KO. Comparing KP and KO, best differentiation was enabled using peaks P72, P97 and P16 with sensitivity/specificity/positive predictive value/negative predictive value of 76.0%, 84.0%, 82.6%, 77.8%, respectively (p &lt; 0.05).DiscussionWe developed a method for the analysis of VOC profiles of bacteria. Using MCC/IMS, we demonstrated that VOCs derived from bacteria are clearly distinguishable from a bare agar plate. Characteristic peaks obtained by MCC/IMS are particularly suitable for the species-specific identification and differentiation of KP and KO. Thus, MCC/IMS might be a useful tool for in vitro diagnostics. Future studies must clarify whether similar patterns of VOCs can be detected in vivo in patients that are colonized or infected with KP or KO to enable rapid and accurate diagnosis of bacterial colonization

    Synthesis, Characterisation, and Preliminary Anti-Cancer Photodynamic Therapeutic \u3ci\u3eIn Vitro\u3c/i\u3e Studies of Mixed-Metal Binuclear Ruthenium(II)-Vanadium(IV) Complexes

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    We report the synthesis and characterisation of mixed-metal binuclear ruthenium(II)-vanadium(IV) complexes, which were used as potential photodynamic therapeutic agents for melanoma cell growth inhibition. The novel complexes, [Ru(pbt)2(phen2DTT)](PF6)2•1.5H2O 1 (where phen2DTT = 1,4-bis(1,10-phenanthrolin-5-ylsulfanyl)butane-2,3-diol and pbt = 2-(2\u27-pyridyl)benzothiazole) and [Ru(pbt)2(tpphz)](PF6)2•3H2O 2 (where tpphz = tetrapyrido[3,2-a:2′,3′-c:3″,2″-h:2‴,3‴-j]phenazine) were synthesised and characterised. Compound 1 was reacted with [VO(sal-L-tryp)(H2O)] (where sal-L-tryp = N-salicylidene-L-tryptophanate) to produce [Ru(pbt)2(phen2DTT)VO(sal-L-tryp)](PF6)2•5H2O 4; while [VO(sal-L-tryp)(H2O)] was reacted with compound 2 to produce [Ru(pbt)2(tpphz)VO(sal-L-tryp)](PF6)2•6H2O 3. All complexes were characterised by elemental analysis, HRMS, ESI MS, UV-visible absorption, ESR spectroscopy, and cyclic voltammetry, where appropriate. In vitro cell toxicity studies (with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay) via dark and light reaction conditions were carried out with sodium diaqua-4,4\u27,4”,4”\u27tetrasulfophthalocyaninecobaltate(II) (Na4[Co(tspc)(H2O)2]), [VO(sal-L-tryp)(phen)]•H2O, and the chloride salts of complexes 3 and 4. Such studies involved A431, human epidermoid carcinoma cells; human amelanotic malignant melanoma cells; and HFF, non-cancerous human skin fibroblast cells. Both chloride salts of complexes 3 and 4 were found to be more toxic to melanoma cells than to non-cancerous fibroblast cells, and preferentially led to apoptosis of the melanoma cells over non-cancerous skin cells. The anti-cancer property of the chloride salts of complexes 3 and 4 was further enhanced when treated cells were exposed to light, while no such effect was observed on non-cancerous skin fibroblast cells. ESR and 51V NMR spectroscopic studies were also used to assess the stability of the chloride salts of complexes 3 and 4 in aqueous media at pH 7.19. This research illustrates the potential for using mixed-metal binuclear ruthenium(II)-vanadium(IV) complexes fighting skin cancer

    Spread of psoriasiform inflammation to remote tissues is restricted by the atypical chemokine receptor ACKR2

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    Elucidating the poorly defined mechanisms by which inflammatory lesions are spatially restricted in vivo, is of critical importance in understanding skin disease. Chemokines are the principal regulators of leukocyte migration and are essential in the initiation and maintenance of inflammation. The membrane-bound psoriasis associated atypical chemokine receptor ACKR2 binds, internalises and degrades most pro-inflammatory CC-chemokines. Here we investigate the role of ACKR2 in limiting the spread of cutaneous psoriasiform inflammation to sites that are remote from the primary lesion.  Circulating factors capable of regulating ACKR2 function at remote sites were identified and examined using a combination of clinical samples, relevant primary human cell cultures, in vitro migration assays and the imiquimod-induced model of psoriasiform skin inflammation. Localised inflammation and IFN together upregulate ACKR2 in remote tissues, protecting them from the spread of inflammation. ACKR2 controls inflammatory T-cell chemotaxis and positioning within the skin, preventing an epidermal influx that is associated with lesion development. Our results have important implications for our understanding of how spatial restriction is imposed on the spread of inflammatory lesions, and highlight systemic ACKR2 induction as a therapeutic strategy in the treatment and prevention of psoriasis and potentially a broad range of other immune-mediated diseases

    The state of the Martian climate

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    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

    A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

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    The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function
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