Fibroblast senescence-associated extracellular matrix promotes heterogeneous lung niche.

Senescent cell accumulation in the pulmonary niche is associated with heightened susceptibility to age-related disease, tissue alterations, and ultimately a decline in lung function. Our current knowledge of senescent cell-extracellular matrix (ECM) dynamics is limited, and our understanding of how senescent cells influence spatial ECM architecture changes over time is incomplete. Herein is the design of an in vitro model of senescence-associated extracellular matrix (SA-ECM) remodeling using a senescent lung fibroblast-derived matrix that captures the spatiotemporal dynamics of an evolving senescent ECM architecture. Multiphoton second-harmonic generation microscopy was utilized to examine the spatial and temporal dynamics of fibroblast SA-ECM remodeling, which revealed a biphasic process that established a disordered and heterogeneous architecture. Additionally, we observed that inhibition of transforming growth factor-ß signaling during SA-ECM remodeling led to improved local collagen fiber organization. Finally, we examined patient samples diagnosed with pulmonary fibrosis to further tie our results of the in vitro model to clinical outcomes. Moreover, we observed that the senescence marker p16 is correlated with local collagen fiber disorder. By elucidating the temporal dynamics of SA-ECM remodeling, we provide further insight on the role of senescent cells and their contributions to pathological ECM remodeling.

The specialist management of non-temporomandibular orofacial pain: maxillofacial surgery's known unknown?

The management of orofacial pain is considered to be within the remit of oral and maxillofacial surgery (OMFS). In this study we aimed to provide an overview of the healthcare "journey" of a group of patients referred to a specialist unit with "complex" non-temporomandibular orofacial pain. We retrospectively reviewed all those who were referred over a six-month period and followed for up to three years. A total of 133 were included, 69% were female, and the mean (SD) duration of symptoms before assessment was 66.4 (88.8) months. Patients were treated for seven different conditions by a mean (SD) of 2.6 (1.2) specialties, and 3.2 (2.5) medications had been tried before assessment at the unit. A mean (SD) of 3.9 (3.3) appointments were attended over the three years, and 80% of patients were prescribed at least one medication. Patients were under the care of the unit for a mean (SD) of 11.9 (14.0) months, and 38% were still being seen at three years. Those with trigeminal neuralgia were most likely to remain in care at three years (p=<0.001), and those with burning mouth syndrome (p=<0.001) or persistent idiopathic facial pain (p=0.005) were most likely to be discharged. In the current NHS climate, the lack of resources to treat facial pain and the focus on a mix of skills, mean that OMF surgeons are likely to have an increasing role in the treatment of these patients. This paper provides an important insight into these conditions.

Is there benefit to continue magnesium sulphate postpartum in women receiving magnesium sulphate before delivery? A randomised controlled study.

OBJECTIVE: To determine if the use of magnesium sulphate postdelivery reduces the risk of eclampsia in women with severe pre-eclampsia exposed to at least 8 hours of magnesium sulphate before delivery. DESIGN: Randomised multicentre controlled trial. SETTING: Latin America. POPULATION: Women with severe pre-eclampsia that had received a 4-g loading dose followed by 1 g per hour for 8 hours as maintenance dose before delivery. METHODS: In all, 1113 women were randomised; 555 women were randomised to continue the infusion of magnesium sulphate for 24 hours postpartum and 558 were randomised to stopping the magnesium sulphate infusion immediately after delivery. OUTCOME MEASURES: Primary outcome was the incidence of eclampsia in the first 24 hours postdelivery. Secondary outcomes included maternal death, maternal complications, time to start ambulation and time to start lactation. RESULTS: The maternal characteristics at randomisation between the groups were not different. There were no differences in the rate of eclampsia; 1/555 (0.18%) versus 2/558 (0.35%) [relative risk (RR 0.7, 95% CI 0.1-3.3; P = 0.50] or maternal complications between the groups (RR 1.0, 95% CI 0.8-1.2; P = 0.76). Time to start ambulation was significantly shorter in the no magnesium sulphate group (18.1 ± 10.6 versus 11.8 ± 10.8 hours; P = 0.0001) and time to start lactation was equally shorter in the no magnesium sulphate group (24.1 ± 17.1 versus 17.1 ± 16.8 hours; P = 0.0001). CONCLUSIONS: Women with severe pre-eclampsia treated with a minimum of 8 hours of magnesium sulphate before delivery do not benefit from continuing the magnesium sulphate for 24 hours postpartum. TWEETABLE ABSTRACT: No benefit of continuing magnesium sulphate postpartum in severe pre-eclampsia exposed to this drug for a minimum of 8 hours before delivery.

Checklists for safe prescribing in oral medicine clinics.

Introduction Prescribing checklists are a means of managing risk related to systemic medications in oral medicine practice.Methods Checklists for workup and monitoring for azathioprine, mycophenolate mofetil (MMF) and dapsone were introduced to an oral medicine clinic. Compliance with the checklists was audited at six and 12-24 months post introduction, and compared to previous clinical practice.Results Azathioprine: compliance with viral serology screening improved from <10% to over 80% at 6 months post checklist introduction, and was 100% at 12 months. Documentation of counselling improved from 48% to 85% at six months, and was 100% at 12 months. Compliance with tuberculosis risk assessment improved from 5% to 50% at six months but declined to 4% at 12 months. Compliance with monitoring blood tests improved slightly. MMF: compliance with viral serology screening increased from nil to 100% at six months. Documented evidence of counselling increased from 20% to 100%. Monitoring blood test compliance for the first six weeks of therapy improved. Dapsone: documentation of patient counselling improved from 25% pre-checklist, to 50% at six months and 60% at 24 months. Monitoring blood test compliance improved at six months but had decreased by 24 months.Discussion and conclusion Clinical checklists led to a modest improvement in prescribing safety in our clinics. The usefulness of checklists depends on cultural changes and clinician engagement. Electronic medication safety programs may be a useful future strategy.

Thermal and spectroscopic studies of the antioxidant food additive propyl gallate.

Literature mentions propyl gallate (PG) as a non-toxic synthetic antioxidant that can be used as a food additive due to its high tolerance to heat. It is important to understand the thermal properties and to identify the decomposition products of this substance, since it has been reported to be thermally stable at temperatures as high as 300 °C. Simultaneous thermogravimetry-differential thermal analysis (TG-DTA), differential scanning calorimetry-photovisual (DSC-photovisual), coupled thermogravimetry-infrared spectroscopy (TG-FTIR) analyses and spectroscopic techniques were used to study the food additive PG. The TG-DTA curves, which were performed with the aid of DSC-photovisual, provided information concerning the thermal stability and decomposition profiles of the compound. From the TG-FTIR coupled techniques, it was possible to identify n-propanol as a possible volatile compound released during the thermal decomposition of the antioxidant. A complete spectroscopic characterization in the ultraviolet, visible, near and middle infrared regions was performed in order to understand the spectroscopic properties of PG.

Quantifying heterogeneity in emphysema from high-resolution computed tomography: a lung tissue research consortium study.

RATIONALE AND OBJECTIVES: To quantify spatial distribution of emphysema using high-resolution computed tomography (HRCT), we applied semiautomated analysis with internal attenuation calibration to measure regional air volume, tissue volume, and fractional tissue volume (FTV = tissue/[air + tissue] volume) in well-characterized patients studied by the Lung Tissue Research Consortium (LTRC). METHODS: HRCT was obtained at supine end-inspiration and end-expiration, and prone end-inspiration from 31 patients with mild, moderate, severe, or very severe emphysema (stages II-V, forced expiratory volume at 1 second >75%, 51%-75%, 21%-50% and ≤20% predicted, respectively). Control data were from 20 healthy non-smokers (stage I). Each lobe was analyzed separately. Heterogeneity of FTV was assessed from coefficients of variation (CV) within and among lobes, and the kurtosis and skewness of FTV histograms. RESULTS: In emphysema, lobar air volume increased up to 177% above normal except in the right middle lobe. Lobar tissue volume increased up to 107% in mild-moderate stages then normalized in advanced stages. Normally, FTV was up to 82% higher in lower than upper lobes. In mild-moderate emphysema, lobar FTV increased by up to 74% above normal at supine inspiration. In severe emphysema, FTV declined below normal in all lobes and positions in correlation with pulmonary function (P < .05). Markers of FTV heterogeneity increased steadily with disease stage in correlation with pulmonary function (P < .05); the pattern is distinct from that seen in interstitial lung disease (ILD). CONCLUSION: CT-derived biomarkers differentiate the spatial patterns of emphysema distribution and heterogeneity from that in ILD. Early emphysema is associated with elevated tissue volume and FTV, consistent with hyperemia, inflammation or atelectasis.

Quantification of regional interstitial lung disease from CT-derived fractional tissue volume: a lung tissue research consortium study.

RATIONALE AND OBJECTIVES: Evaluation of chest computed tomography (CT) is usually qualitative or semiquantitative, resulting in subjective descriptions often by different observers over time and imprecise determinations of disease severity within distorted lobes. There is a need for standardized imaging biomarkers to quantify regional disease, maximize diagnostic yield, and facilitate multicenter comparisons. We applied lobe-based voxelwise image analysis to derive regional air (Vair) and tissue (Vtissue) volumes and fractional tissue volume (FTV = tissue/[tissue+air] volume) as internally standardized parameter for assessing interstitial lung disease (ILD). MATERIALS AND METHODS: High-resolution CT was obtained at supine and prone end-inspiration and supine end-expiration in 29 patients with ILD and 20 normal subjects. Lobar Vair, Vtissue, and FTV were expressed along standard coordinate axes. RESULTS: In normal subjects from end-inspiration to end-expiration, total Vair declined ~43%, FTV increased ~80%, but Vtissue remained unchanged. With increasing ILD, Vair declined and Vtissue rose in all lobes; FTV increased with a peripheral-to-central progression inversely correlated to spirometry and lung diffusing capacity (r(2) = 0.57-0.75, prone end-inspiration). Inter- and intralobar coefficients of variation of FTV increased 84-148% in mild-to-moderate ILD, indicating greater spatial heterogeneity, then normalized in severe ILD. Analysis of discontinuous images incurs <3% error compared to consecutive images. CONCLUSIONS: These regional attenuation-based biomarkers could quantify heterogeneous parenchymal disease in distorted lobes, detect mild ILD involvement in all lobes and describe the pattern of disease progression. The next step would be to study a larger series, examine reproducibility and follow longitudinal changes in correlation with clinical and functional indices.