| 238581. |
- Smith, L. E., et al.
(författare)
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The Biology of Retinopathy of Prematurity How Knowledge of Pathogenesis Guides Treatment
- 2013
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Ingår i: Clinics in Perinatology. - : Elsevier BV. - 0095-5108. ; 40:2
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Tidskriftsartikel (refereegranskat)abstract
- Retinopathy of prematurity occurs because the retina of a preterm infant at birth is incompletely vascularized, and if the postnatal environment does not match the in utero environment that supported retinal development, the vessels and neural retina will not grow normally. Risk factors determined from many clinical studies and animal studies fall into 2 categories: prenatal factors and postnatal factors.
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| 238582. |
- Smith, Lucy K., et al.
(författare)
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An International Comparison of Death Classification at 22 to 25 Weeks' Gestational Age
- 2018
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Ingår i: Pediatrics. - : AMER ACAD PEDIATRICS. - 0031-4005 .- 1098-4275. ; 142:1
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To explore international differences in the classification of births at extremely low gestation and the subsequent impact on the calculation of survival rates.METHODS: We used national data on births at 22 to 25 weeks' gestation from the United States (2014; n = 11144), Canada (2009-2014; n = 5668), the United Kingdom (2014-2015; n = 2992), Norway (2010-2014; n = 409), Finland (2010-2015; n = 348), Sweden (2011-2014; n = 489), and Japan (2014-2015; n = 2288) to compare neonatal survival rates using different denominators: all births, births alive at the onset of labor, live births, live births surviving to 1 hour, and live births surviving to 24 hours.RESULTS: For births at 22 weeks' gestation, neonatal survival rates for which we used live births as the denominator varied from 3.7% to 56.7% among the 7 countries. This variation decreased when the denominator was changed to include stillbirths (ie, all births [1.8%-22.3%] and fetuses alive at the onset of labor [3.7%-38.2%]) or exclude early deaths and limited to births surviving at least 12 hours (50.0%-77.8%). Similar trends were seen for infants born at 23 weeks' gestation. Variation diminished considerably at 24 and 25 weeks' gestation.CONCLUSIONS: International variation in neonatal survival rates at 22 to 23 weeks' gestation diminished considerably when including stillbirths in the denominator, revealing the variation arises in part from differences in the proportion of births reported as live births, which itself is closely connected to the provision of active care.
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| 238583. |
- Smith, Margaretha E., et al.
(författare)
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Endotoxin Exposure Increases LL-37 - But Not Calprotectin - In Healthy Human Airways
- 2017
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Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 9:5, s. 475-482
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: The antimicrobial peptides (AMPs) LL-37 and calprotectin are important players in the innate immunity of human airways. In patients with diseases characterized by bacterial colonization, the airway concentrations of these AMPs are increased. Less is known about their presence and release patterns in healthy humans. Our aim was to determine whether LL-37 and calprotectin are released after the activation of the innate immune response in the peripheral airways. Methods: Healthy volunteers underwent exposure to endotoxin and vehicle in contralateral segment bronchi. After 12 or 24 h, samples of bronchoalveolar lavage fluid (BALf) were collected bilaterally from exposed segments. Cell and AMP concentrations were assessed, as were the pro-form and active form of LL-37. Results: Both LL-37 and calprotectin were detected in cell-free BALf from both endotoxin- and vehicle-exposed segments. The concentrations of precursor and active LL-37 and neutrophils were significantly higher in endotoxin-exposed segments after 12 and 24 h, and the concentrations of LL-37 and neutrophils correlated positively. The concentrations of calprotectin were not markedly affected by exposure to endotoxin. Conclusions: Local endotoxin exposure elicits the release and activation of LL-37 but not calprotectin in healthy human peripheral airways, suggesting an inducible involvement of LL-37 in the local innate immune response. © 2017 S. Karger AG, Basel. Copyright: All rights reserved.
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| 238584. |
- Smith, Margaretha E.
(författare)
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Endotoxin-induced inflammation in healthy human airways
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to investigate the innate immune response in healthy human airways in vivo after simulation of a Gram-negative infection. Intrabronchial exposure to the TLR4 agonist endotoxin was used as a model for the innate mechanisms in the immune response that are caused by cigarette smoke and by natural infection with Gram-negative bacteria. Endotoxin is part of the outer cell wall of these bacteria and is one of many components of cigarette smoke. Healthy volunteers were exposed to endotoxin and phosphate buffered saline in contralateral lung segments during bronchoscopy. Bilateral bronchoalveolar lavages (BAL) were then performed at different time points thereafter. Inflammatory cells and soluble mediators involved in the inflammatory response were analyzed in BAL samples. The exposure of healthy airways to endotoxin led to a prompt increase in proinflammatory mediators as well as to an influx of inflammatory cells, a process that receded within days. In the first study, the proteolytic homeostasis of the healthy human lung was evaluated, where endotoxin induced a net activity of serine proteases, but not of gelatinases. In the second study, an endotoxin-induced increase of the neutrophil recruiting cytokine IL-17 and the presence and endotoxin-induced increase of IL-17-producing memory T-helper cells of a unique phenotype were shown. In the third study, the presence and endotoxin-induced increase of another cytokine, IL-26, was demonstrated. IL-26 was re-vealed to be expressed by macrophages and to exert chemotaxis on neutrophils. The fourth study analyzed effects of endotoxin on antimicrobial peptides (AMPs), possible candidates for options for new treatment of infectious diseases. Endotoxin did increase the levels of LL-37, but not those of Calprotectin. In conclusion, the delicate balance of tissue degrading enzymes and their in-hibitors is disrupted by a transient stimulus, resembling the initial phase of an inflammation. It is open to speculation as to whether repeated or continuous stimuli of this kind may contribute to the imbalance in proteolytic homeostasis that is a common denominator for chronic inflammatory lung diseases. It can also be concluded that interleukins that are integrated with the innate immunity are involved in the response to endotoxin in healthy human lungs. The findings on interleukins and AMPs may be used to target new drugs for inflammatory diseases and infections.
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| 238585. |
- Smith, Michael, et al.
(författare)
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Human sleep and cortical reactivity are influenced by lunar phase
- 2014
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 24:12, s. R551-552
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Tidskriftsartikel (refereegranskat)abstract
- Various human biological functions adhere to a circadian rhythm that to some extent may be affected by environmental factors, including light and temperature [1]. Recent evidence from Cajochen et al. [2] indicates that human sleep is influenced by the cycle of the moon, measured in conditions precluding the potential impact of nocturnal lunar illumination Here in a similarly retrospective study of 47 healthy volunteers (mean age 23.3, S.D. ±2.9 years) we demonstrate that total sleep time decreases by 25 minutes and cortical reactivity to environmental stimuli during sleep increases around full moon, and rapid eye movement (REM) sleep latency lengthens by 30 minutes around new moon. The findings strengthen the notion that human sleep is modulated by lunar phase but point to important deviations from the study of Cajochen et al. that need to be addressed, particularly with regard to individual susceptibility.
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| 238586. |
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| 238587. |
- Smith, Matthew R W, et al.
(författare)
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Increased Cartilage Oligomeric Matrix Protein Concentrations in Equine Digital Flexor Tendon Sheath Synovial Fluid Predicts Intrathecal Tendon Damage.
- 2011
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Ingår i: Veterinary surgery : VS : the official journal of the American College of Veterinary Surgeons. - 1532-950X. ; Dec, s. 54-58
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate digital flexor tendon sheath (DFTS) synovial fluid cartilage oligomeric matrix protein (COMP) concentrations as a molecular marker for intrathecal pathology. Study Design: Case control study. Animals: Horses (n=46) with DFTS tenosynovitis; 23 fresh cadaver horses. Methods: DFTS synovial fluid samples were collected from clinical cases with noninfected DFTS tenosynovitis and from control DFTS. Clinical and surgical findings were recorded, and dissection of control limbs was performed to confirm the DFTS to be grossly normal. Synovial fluid COMP was quantified using a homologous competitive inhibition ELISA. Results: Abnormalities were identified tenoscopically: intrathecal tendon/ligament tearing was identified in 37 cases and 9 had other lesions. In control horses, synovial fluid COMP was higher in younger horses. Clinical cases with intrathecal tendon/ligament tearing had higher synovial fluid COMP than either clinical cases with other lesions, or controls. In horses ≥5 years old, the sensitivity and specificity of the assay was high for diagnosing intrathecal tendon/ligament tearing. Conclusions: COMP concentrations in DFTS synovial fluid were significantly greater than those in normal horses with noninfected tenosynovitis caused by intrathecal tendon/ligament tearing, but not by other lesions.
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| 238588. |
- Smith, M. T., et al.
(författare)
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Sex differences in measures of central sensitization and pain sensitivity to experimental sleep disruption : implications for sex differences in chronic pain
- 2019
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Ingår i: Sleep. ; 42:2
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Tidskriftsartikel (refereegranskat)abstract
- STUDY OBJECTIVES: Females demonstrate heightened central sensitization (CS), a risk factor for chronic pain characterized by enhanced responsivity of central nervous system nociceptors to normal or subthreshold input. Sleep disruption increases pain sensitivity, but sex has rarely been evaluated as a moderator and few experiments have measured CS. We evaluated whether two nights of sleep disruption alter CS measures of secondary hyperalgesia and mechanical temporal summation in a sex-dependent manner. We also evaluated differences in measures of pain sensitivity. METHODS: Seventy-nine healthy adults (female n = 46) participated in a randomized crossover experiment comparing two consecutive nights of eight pseudorandomly distributed forced awakenings (FA [-200 min sleep time]) against two nights of undisturbed sleep (US). We conducted sensory testing the mornings following Night 2; the heat-capsaicin pain model was used to induce secondary hyperalgesia. RESULTS: FA reduced total sleep time (REM and NREM Stage 3) more profoundly in males. We observed divergent, sex-dependent effects of FA on secondary hyperalgesia and temporal summation. FA significantly increased secondary hyperalgesia in males and significantly increased temporal summation in females. Sex differences were not attributable to differential sleep loss in males. FA also significantly reduced heat-pain threshold and cold pressor pain tolerance, independently of sex. CONCLUSIONS: Sleep disruption enhances different pain facilitatory measures of CS in males and females suggesting that sleep disturbance may increase risk for chronic pain in males and females via distinct pathways. Findings have implications for understanding sex differences in chronic pain and investigating sleep in chronic pain prevention efforts.
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| 238589. |
- Smith Malm, Christofer, et al.
(författare)
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Survey of an online system for information to women with epilepsy of childbearing age and management during pregnancy: A 3-year evaluation
- 2024
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Ingår i: EPILEPSIA OPEN. - 2470-9239.
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveWe developed an online tool for women with epilepsy consisting of two modules: one with information on pregnancy-related issues (information module) and one for reminders about blood test and communication about dose changes (pregnancy module). Our aim was to assess perceived value, user-friendliness and improvement of patient knowledge in users.MethodsThe system was launched in 2019 and patients invited by epilepsy nurses were asked to participate in a survey 1 month after the invitation for the information module, and 1 month postnatally for the pregnancy module.ResultsBy November 2022, the system had been used by 96 individuals out of 100 invited in the pregnancy module, in a total of 114 pregnancies. One hundred and eleven women had been invited to the information module, and 70 of these accessed it. The survey received 96 answers (44 information, 52 pregnancy). User-friendliness was rated as good or very good by a little over half of the users; 55% in the information module and 52% in the pregnancy module. Among pregnant women, 83% found the TDM part useful and most would prefer a similar system in future pregnancies. Sixty-four percent of users of the information module and 48% of the pregnancy module found that the system had increased their knowledge. Two knowledge questions were answered correctly by a significantly higher proportion of those that had accessed the online information.SignificanceThere was great demand for online communication during pregnancy and our experiences of implementation can hopefully assist digitalization of epilepsy care elsewhere. Online information also seems to increase knowledge about pregnancy-related issues, but our invitation-only method of inclusion was not effective for widespread dissemination. Patient-initiated access with optional epilepsy-team contact if questions arise could be an alternative.Plain Language SummaryWe have performed a survey of users of a new Internet-based tool for information to women of childbearing age and communication about dose changes during pregnancy. Users were overall satisfied with the tool and answered some knowledge questions more accurately after accessing the information.
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| 238590. |
- Smith, N. M., et al.
(författare)
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Statistical Parametric Mapping in Amyloid Positron Emission Tomography
- 2022
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD), the most common cause of dementia, has limited treatment options. Emerging disease modifying therapies are targeted at clearing amyloid-β (Aβ) aggregates and slowing the rate of amyloid deposition. However, amyloid burden is not routinely evaluated quantitatively for purposes of disease progression and treatment response assessment. Statistical Parametric Mapping (SPM) is a technique comparing single-subject Positron Emission Tomography (PET) to a healthy cohort that may improve quantification of amyloid burden and diagnostic performance. While primarily used in 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-PET, SPM’s utility in amyloid PET for AD diagnosis is less established and uncertainty remains regarding optimal normal database construction. Using commercially available SPM software, we created a database of 34 non-APOE ε4 carriers with normal cognitive testing (MMSE > 25) and negative cerebrospinal fluid (CSF) AD biomarkers. We compared this database to 115 cognitively normal subjects with variable AD risk factors. We hypothesized that SPM based on our database would identify more positive scans in the test cohort than the qualitatively rated [11C]-PiB PET (QR-PiB), that SPM-based interpretation would correlate better with CSF Aβ42 levels than QR-PiB, and that regional z-scores of specific brain regions known to be involved early in AD would be predictive of CSF Aβ42 levels. Fisher’s exact test and the kappa coefficient assessed the agreement between SPM, QR-PiB PET, and CSF biomarkers. Logistic regression determined if the regional z-scores predicted CSF Aβ42 levels. An optimal z-score cutoff was calculated using Youden’s index. We found SPM identified more positive scans than QR-PiB PET (19.1 vs. 9.6%) and that SPM correlated more closely with CSF Aβ42 levels than QR-PiB PET (kappa 0.13 vs. 0.06) indicating that SPM may have higher sensitivity than standard QR-PiB PET images. Regional analysis demonstrated the z-scores of the precuneus, anterior cingulate and posterior cingulate were predictive of CSF Aβ42 levels [OR (95% CI) 2.4 (1.1, 5.1) p = 0.024; 1.8 (1.1, 2.8) p = 0.020; 1.6 (1.1, 2.5) p = 0.026]. This study demonstrates the utility of using SPM with a “true normal” database and suggests that SPM enhances diagnostic performance in AD in the clinical setting through its quantitative approach, which will be increasingly important with future disease-modifying therapies.
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