Patients with resolution of low-lying placenta and placenta previa remain at increased risk of postpartum hemorrhage.

OBJECTIVE: To determine whether women who experience resolution of low placentation (low-lying placenta or placenta previa) are at increased risk of postpartum hemorrhage compared to those with normal placentation throughout pregnancy. METHODS: This was a retrospective cohort study of women who delivered at Mount Sinai Hospital between 2015 and 2019, and who were diagnosed with low-lying placenta or placenta previa on transvaginal ultrasound at the time of the second-trimester anatomical survey, with resolution of low placentation on subsequent ultrasound examination. Women undergoing second-trimester anatomical survey who had normal placentation on transvaginal ultrasound 3 days before or after the cases were randomly identified for comparison. The primary outcome was the rate of postpartum hemorrhage. Secondary outcomes included the need for a blood transfusion, use of additional uterotonic medication, the need for additional procedures to control bleeding, and maternal admission to the intensive care unit. Outcomes were assessed using a multivariable logistic regression model. RESULTS: A total of 1256 women were identified for analysis, of whom 628 had resolved low placentation and 628 had normal placentation. Women with resolved low placentation, compared to those with normal placentation throughout pregnancy, had significantly higher mean age (33.0 ± 5.4 years vs 31.9 ± 5.5 years; P < 0.01) and lower mean body mass index at delivery (27.9 ± 5.5 kg/m2 vs 30.2 ± 5.7 kg/m2 ; P < 0.01), and were more likely to have undergone in-vitro fertilization, be of non-Hispanic white race, have posterior placental location (all P < 0.01) and have private/commercial health insurance (P = 0.04). Patients with resolved low placentation vs normal placentation had greater odds of postpartum hemorrhage (adjusted odds ratio (aOR), 3.5 (95% CI, 2.0-6.0); P < 0.01), use of additional uterotonic medication (aOR, 2.2 (95% CI, 1.5-3.1); P < 0.01) and increased rates of additional procedures to control bleeding (aOR, 4.0 (95% CI, 1.3-11.9); P = 0.01). CONCLUSION: Despite high rates of resolution of low-lying placenta and placenta previa by term, women with resolved low placentation remain at increased risk of postpartum hemorrhage compared to those with normal placentation throughout pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Evaluation of oncogenic cysteinyl leukotriene receptor 2 as a therapeutic target for uveal melanoma.

Uveal melanoma is a rare, but deadly, form of eye cancer that arises from melanocytes within the uveal tract. Although advances have emerged in treatment of the primary tumour, patients are still faced with vision loss, eye enucleation and lethal metastatic spread of the disease. Approximately 50% of uveal melanoma patients develop metastases, which occur most frequently in the liver. Metastatic patients encounter an extremely poor prognosis; as few as 8% survive beyond 2 years. Understanding of the genetic underpinnings of this fatal disease evolved in recent years with the identification of new oncogenic mutations that drive uveal melanoma pathogenesis. Despite this progress, the lack of successful therapies or a proven standard-of-care for uveal melanoma highlights the need for new targeted therapies. This review focuses on the recently identified CYSLTR2 oncogenic mutation in uveal melanoma. Here, we evaluate the current status of uveal melanoma and investigate how to better understand the role of this CYSLTR2 mutation in the disease and implications for patients harbouring this mutation.

Effects of human rhinovirus on epithelial barrier integrity and function in children with asthma.

BACKGROUND: Bronchial epithelial tight junctions (TJ) have been extensively assessed in healthy airway epithelium. However, no studies have yet assessed the effect of human rhinovirus (HRV) infection on the expression and resultant barrier function in epithelial tight junctions (TJ) in childhood asthma. OBJECTIVES: To investigate the impact of HRV infection on airway epithelial TJ expression and barrier function in airway epithelial cells (AECs) of children with and without asthma. Furthermore, to test the hypothesis that barrier integrity and function is compromised to a greater extent by HRV in AECs from asthmatic children. METHODS: Primary AECs were obtained from children with and without asthma, differentiated into air-liquid interface (ALI) cultures and infected with rhinovirus. Expression of claudin-1, occludin and zonula occluden-1 (ZO-1) was assessed via qPCR, immunocytochemistry (ICC), in-cell western (ICW) and confocal microscopy. Barrier function was assessed by transepithelial electrical resistance (TER; RT ) and permeability to fluorescent dextran. RESULTS: Basal TJ gene expression of claudin-1 and occludin was significantly upregulated in asthmatic children compared to non-asthmatics; however, no difference was seen with ZO-1. Interestingly, claudin-1, occludin and ZO-1 protein expression was significantly reduced in AEC of asthmatic children compared to non-asthmatic controls suggesting possible post-transcriptional inherent differences. HRV infection resulted in a transient dissociation of TJ and airway barrier integrity in non-asthmatic children. Although similar dissociation of TJ was observed in asthmatic children, a significant and sustained reduction in TJ expression concurrent with both a significant decrease in TER and an increase in permeability in asthmatic children was observed. CONCLUSION: This study demonstrates novel intrinsic differences in TJ gene and protein expression between AEC of children with and without asthma. Furthermore, it correlates directly the relationship between HRV infection and the resultant dissociation of epithelial TJ that causes a continued altered barrier function in children with asthma.

A community laboratory drop-off option for bowel screening test kits increases participation rates: results from an interrupted time series analysis.

Background: Countries with population-based colorectal cancer screening using faecal occult blood test kits performed in the home and posted to the laboratory struggle to achieve higher than 60% uptake. We measured the impact on participation of offering a community laboratory drop-off (CLD) alternative to postal return in New Zealand's Bowel Screening Pilot. Methods: From May to September, 2015, a flyer added to the bowel screening test kit offered CLD as an alternative to returning the kit by post. Participation rates for equal-length periods before and after were measured. Interrupted time series and logistic regression models measured CLD-attributable the changes in screening participation. Results: Overall, 26% of invitees used the CLD option. The effect of the CLD option on participation varied significantly by age, gender and ethnicity. There was a significant increase in participation among males (+1.75%; P = 0.002); patients under 60 (+1.65%; P = 0.006); Maori and Pacific (+2.88%; P = 0.029); and in the European/other ethnic group (+1.04%; P = 0.045) but not in Asians. Conclusions: Both analyses showed that at little or no additional cost, the CLD option produced small but significant increases in participation for non-Asian men and younger invitees. A CLD kit return option may have benefits for other bowel screening programmes.

Echocardiographic determination of resting haemodynamics and optimal positioning in term pregnant women.

Optimal positioning for anaesthesia in pregnant women involves balancing the need for ideal tracheal intubation conditions (achieved by the head elevated ramped position), with the prevention of reduced cardiac output from aortocaval compression (achieved by left lateral pelvic tilt). No studies have examined the effect on cardiac output of left lateral pelvic tilt in the ramped position. We studied non-labouring, non-anaesthetised healthy term pregnant women who underwent baseline (left lateral decubitus) cardiac assessment using transthoracic echocardiography. We then compared cardiac output, maternal physiological variables, fetal heart rate and comfort scores in three positions: left lateral decubitus; ramped position with wedge; and ramped position alone. Thirty women completed the study. Mean (SD) age, gestation and body mass index were 33.5 (3.93) years, 38.5 (0.94) weeks and 29.0 (4.0) kg.m-2 , respectively. Mean ejection fraction, left ventricular internal diameter and mitral valve E/e' were 55.2 (6.8) %, 4.70 (0.43) cm and 7.50 (1.82), respectively. There were no differences in cardiac output between the positions (p = 0.503). There were no differences in systolic (p = 0.955) or diastolic (p = 0.987) blood pressure, maternal heart rate (p = 0.133), oxygen saturation, respiratory rate (p = 0.964) or fetal heart rate (p = 0.361) between ramped with wedge and ramped alone positions. Left lateral decubitus was most comfortable (p = 0.001), however, there were no differences in comfort levels between ramped with wedge and ramped alone positions. The ramped position without left lateral tilt is safe and acceptable in non-labouring, non-anaesthetised, healthy term pregnant women. Left lateral pelvic tilt may be unnecessary in the head elevated ramped position in term pregnant women.

REBOA at Role 2 Afloat: resuscitative endovascular balloon occlusion of the aorta as a bridge to damage control surgery in the military maritime setting.

Role 2 Afloat provides a damage control resuscitation and surgery facility in support of maritime, littoral and aviation operations. Resuscitative endovascular balloon occlusion of the aorta (REBOA) offers a rapid, effective solution to exsanguinating haemorrhage from pelvic and non-compressible torso haemorrhage. It should be considered when the patient presents in a peri-arrest state, if surgery is likely to be delayed, or where the single operating table is occupied by another case. This paper will outline the data in support of endovascular haemorrhage control, describe the technique and explore how REBOA could be delivered using equipment currently available in the Royal Navy Role 2 Afloat equipment module. Also discussed are potential future directions in endovascular resuscitation.

The value of routine screening mammography in women aged 35-39 years in a symptomatic breast unit.

AIM: To determine the breast cancer detection rate at routine bilateral screening mammography in women aged 35-39 years attending a symptomatic breast clinic, in women of population-risk profile with a normal clinical examination. METHODS AND MATERIALS: A retrospective analysis of all mammograms performed on patients aged 35-39 years at St James's Hospital from 2011-2015 was carried out. Patients with moderate or high familial risk of breast cancer, personal breast cancer history or chest radiation, males, general practitioner (GP) and internal hospital referrals, and those with abnormal clinical examinations were excluded. Included women had "normal", "benign", or undocumented examination findings. Results of imaging, including ultrasound and histopathological results, were recorded. Information was extracted from the hospital's electronic record systems. RESULTS: Of 4,087 patients aged 35-39 who had bilateral mammograms from 2011-2015, 2,148 patients were excluded from analysis. Of 1,939 included women, four (0.21%) were diagnosed with breast cancer confirmed at histology based on mammographic findings: two invasive ductal carcinoma (8 and 2 mm) and two ductal carcinoma in situ (DCIS; 4.5 mm high-grade DCIS and 2 mm low-grade DCIS). Other histological findings included two B3, 46 B2, and three B1 lesions. Overall, 115 biopsies were performed in this cohort; 55 (47.8%) were attributable to mammographic screening, producing a biopsy rate of 2.8% due to mammography alone. CONCLUSION: Per 1,000 women screened, 2.1 cases of cancer were detected. This figure would be below accepted international thresholds to undertake screening mammography and raises radiation protection issues. Additionally, a large number of benign biopsies were undertaken, with likely resultant psychological impact. Further studies could inform national guidance.

Impaired airway epithelial cell responses from children with asthma to rhinoviral infection.

BACKGROUND: The airway epithelium forms an effective immune and physical barrier that is essential for protecting the lung from potentially harmful inhaled stimuli including viruses. Human rhinovirus (HRV) infection is a known trigger of asthma exacerbations, although the mechanism by which this occurs is not fully understood. OBJECTIVE: To explore the relationship between apoptotic, innate immune and inflammatory responses to HRV infection in airway epithelial cells (AECs) obtained from children with asthma and non-asthmatic controls. In addition, to test the hypothesis that aberrant repair of epithelium from asthmatics is further dysregulated by HRV infection. METHODS: Airway epithelial brushings were obtained from 39 asthmatic and 36 non-asthmatic children. Primary cultures were established and exposed to HRV1b and HRV14. Virus receptor number, virus replication and progeny release were determined. Epithelial cell apoptosis, IFN-ß production, inflammatory cytokine release and epithelial wound repair and proliferation were also measured. RESULTS: Virus proliferation and release was greater in airway epithelial cells from asthmatics but this was not related to the number of virus receptors. In epithelial cells from asthmatic children, virus infection dampened apoptosis, reduced IFN-ß production and increased inflammatory cytokine production. HRV1b infection also inhibited wound repair capacity of epithelial cells isolated from non-asthmatic children and exaggerated the defective repair response seen in epithelial cells from asthmatics. Addition of IFN-ß restored apoptosis, suppressed virus replication and improved repair of airway epithelial cells from asthmatics but did not reduce inflammatory cytokine production. CONCLUSIONS: Collectively, HRV infection delays repair and inhibits apoptotic processes in epithelial cells from non-asthmatic and asthmatic children. The delayed repair is further exaggerated in cells from asthmatic children and is only partially reversed by exogenous IFN-ß.

Glucagon increases energy expenditure independently of brown adipose tissue activation in humans.

AIMS: To investigate, for a given energy expenditure (EE) rise, the differential effects of glucagon infusion and cold exposure on brown adipose tissue (BAT) activation in humans. METHODS: Indirect calorimetry and supraclavicular thermography was performed in 11 healthy male volunteers before and after: cold exposure; glucagon infusion (at 23 °C); and vehicle infusion (at 23 °C). All volunteers underwent (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/CT scanning with cold exposure. Subjects with cold-induced BAT activation on (18)F-FDG PET/CT (n = 8) underwent a randomly allocated second (18)F-FDG PET/CT scan (at 23 °C), either with glucagon infusion (n = 4) or vehicle infusion (n = 4). RESULTS: We observed that EE increased by 14% after cold exposure and by 15% after glucagon infusion (50 ng/kg/min; p < 0.05 vs control for both). Cold exposure produced an increase in neck temperature (+0.44 °C; p < 0.001 vs control), but glucagon infusion did not alter neck temperature. In subjects with a cold-induced increase in the metabolic activity of supraclavicular BAT on (18)F-FDG PET/CT, a significant rise in the metabolic activity of BAT after glucagon infusion was not detected. Cold exposure increased sympathetic activation, as measured by circulating norepinephrine levels, but glucagon infusion did not. CONCLUSIONS: Glucagon increases EE by a similar magnitude compared with cold activation, but independently of BAT thermogenesis. This finding is of importance for the development of safe treatments for obesity through upregulation of EE.

Effect of anaesthetic technique on the natural killer cell anti-tumour activity of serum from women undergoing breast cancer surgery: a pilot study.

BACKGROUND: Animal models and retrospective clinical data suggest that certain anaesthetic techniques can attenuate immunosuppression and minimize metastasis after cancer surgery. Natural killer (NK) T cells are a critical component of the anti-tumour immune response. We investigated the effect of serum from women undergoing primary breast cancer surgery, randomized to propofol-paravertebral block (PPA) or sevoflurane-opioid (GA) anaesthetic techniques, on healthy human donor NK cell function and cytotoxicity against oestrogen and progesterone receptor-positive breast cancer cells (HCC1500). METHODS: Ten subjects who donated serum before operation and 24 h after operation in an ongoing randomized prospective trial (NCT 00418457) were randomly selected. Serum from PPA (n=5) and GA (n=5) subjects was co-cultured with HCC1500 and healthy primary NK cells. NK cell activating receptors (NKp30, NKp44, NKp46, 2b4, CD16, NKG2D), cytokine production, NK CD107a expression, and cytotoxicity towards HCC1500 were examined. RESULTS: Serum from PPA subjects did not alter normal NK marker expression or secretion of cytokines. Serum from GA subjects reduced NK cell activating receptor CD16 [from mean (sem), 82 (2)% to 50 (4)%, P=0.001], IL-10 [from 1700 (80) to 1200 (92) pg ml(-1), P=0.001], and IL-1ß [from 68 (12) to 19 (4) pg ml(-1), P=0.01]. An increase in NK cell CD107a [23 (2)% to 37(3)%, P=0.007] and apoptosis of HCC1500 [11 (1)% to 21 (2)%, P=0.0001] was observed with PPA serum, but not GA serum, treated NK cells. CONCLUSION: Serum from women with breast cancer undergoing surgical excision who were randomized to receive a PPA anaesthetic technique led to greater human donor NK cell cytotoxicity in vitro compared with serum from women who received GA. CLINICAL TRIAL REGISTRATION: NCT 041857.

Mapping neurodevelopment with sleep macro- and micro-architecture across multiple pediatric populations.

Profiles of sleep duration and timing and corresponding electroencephalographic activity reflect brain changes that support cognitive and behavioral maturation and may provide practical markers for tracking typical and atypical neurodevelopment. To build and evaluate a sleep-based, quantitative metric of brain maturation, we used whole-night polysomnography data, initially from two large National Sleep Research Resource samples, spanning childhood and adolescence (total N = 4,013, aged 2.5 to 17.5 years): the Childhood Adenotonsillectomy Trial (CHAT), a research study of children with snoring without neurodevelopmental delay, and Nationwide Children's Hospital (NCH) Sleep Databank, a pediatric sleep clinic cohort. Among children without neurodevelopmental disorders (NDD), sleep metrics derived from the electroencephalogram (EEG) displayed robust age-related changes consistently across datasets. During non-rapid eye movement (NREM) sleep, spindles and slow oscillations further exhibited characteristic developmental patterns, with respect to their rate of occurrence, temporal coupling and morphology. Based on these metrics in NCH, we constructed a model to predict an individual's chronological age. The model performed with high accuracy (r = 0.93 in the held-out NCH sample and r = 0.85 in a second independent replication sample - the Pediatric Adenotonsillectomy Trial for Snoring (PATS)). EEG-based age predictions reflected clinically meaningful neurodevelopmental differences; for example, children with NDD showed greater variability in predicted age, and children with Down syndrome or intellectual disability had significantly younger brain age predictions (respectively, 2.1 and 0.8 years less than their chronological age) compared to age-matched non-NDD children. Overall, our results indicate that sleep architectureoffers a sensitive window for characterizing brain maturation, suggesting the potential for scalable, objective sleep-based biomarkers to measure neurodevelopment.

Replication enhancer elements within the open reading frame of tick-borne encephalitis virus and their evolution within the Flavivirus genus.

We provide experimental evidence of a replication enhancer element (REE) within the capsid gene of tick-borne encephalitis virus (TBEV, genus Flavivirus). Thermodynamic and phylogenetic analyses predicted that the REE folds as a long stable stem-loop (designated SL6), conserved among all tick-borne flaviviruses (TBFV). Homologous sequences and potential base pairing were found in the corresponding regions of mosquito-borne flaviviruses, but not in more genetically distant flaviviruses. To investigate the role of SL6, nucleotide substitutions were introduced which changed a conserved hexanucleotide motif, the conformation of the terminal loop and the base-paired dsRNA stacking. Substitutions were made within a TBEV reverse genetic system and recovered mutants were compared for plaque morphology, single-step replication kinetics and cytopathic effect. The greatest phenotypic changes were observed in mutants with a destabilized stem. Point mutations in the conserved hexanucleotide motif of the terminal loop caused moderate virus attenuation. However, all mutants eventually reached the titre of wild-type virus late post-infection. Thus, although not essential for growth in tissue culture, the SL6 REE acts to up-regulate virus replication. We hypothesize that this modulatory role may be important for TBEV survival in nature, where the virus circulates by non-viraemic transmission between infected and non-infected ticks, during co-feeding on local rodents.

Balloons on the battlefield: REBOA implementation in the UK Defence Medical Services.

Established in 2018, the Defence Endovascular Resuscitation (DefER) group recognised that resuscitative endovascular balloon occlusion of the aorta (REBOA) offered an option to improve survival in battle casualties dying from haemorrhage, particularly in remote and austere surgical settings. Following a successful jHub opportunity assessment, DefER purchased training and operational kit at pace. By 1 April 2019, the first forward surgical group undertook a bespoke endovascular training and assessment package. Results of the pilot were presented back to a jHub 4* Innovation Board, which initially awarded £500 000 to fund the project to full implementation. Med Op Cap provided a solution to establish REBOA as a core capability on to the 370 modules. REBOA catheters and arterial access kit are now available to deployed Role 2 facilities across defence as an adjunct to damage control resuscitation in specific circumstances. REBOA has, from a standing start, gained pan-Defence Medical Services (DMS) endorsement and has been integrated into deployed damage control resuscitation. To establish a new resuscitation capability across all Role 2 platforms within 15 months of inception represents implementation at pace. This agility was unlocked by empowering clinicians to develop the platform in conjunction with commercial procurement. This article describes how this innovative pathway facilitated the rapid introduction of a lifesaving haemorrhage control technique to equip DMS clinicians.

Spindle Chirp and other Sleep Oscillatory Features in Young Children with Autism.

Objectives: To determine whether spindle chirp and other sleep oscillatory features differ in young children with and without autism. Methods: Automated processing software was used to re-assess an extant set of polysomnograms representing 121 children (91 with autism [ASD], 30 typically-developing [TD]), with an age range of 1.35-8.23 years. Spindle metrics, including chirp, and slow oscillation (SO) characteristics were compared between groups. SO and fast and slow spindle (FS, SS) interactions were also investigated. Secondary analyses were performed assessing behavioural data associations, as well as exploratory cohort comparisons to children with non-autism developmental delay (DD). Results: Posterior FS and SS chirp was significantly more negative in ASD than TD. Both groups had comparable intra-spindle frequency range and variance. Frontal and central SO amplitude were decreased in ASD. In contrast to previous manual findings, no differences were detected in other spindle or SO metrics. The ASD group displayed a higher parietal coupling angle. No differences were observed in phase-frequency coupling. The DD group demonstrated lower FS chirp and higher coupling angle than TD. Parietal SS chirp was positively associated with full developmental quotient. Conclusions: For the first time spindle chirp was investigated in autism and was found to be significantly more negative than in TD in this large cohort of young children. This finding strengthens previous reports of spindle and SO abnormalities in ASD. Further investigation of spindle chirp in healthy and clinical populations across development will help elucidate the significance of this difference and better understand this novel metric.

Antimicrobial usage in an intensive care unit: a prospective analysis.

Antimicrobial therapies in the Intensive Care Unit (ICU) need to be appropriate in both their antimicrobial cover and duration. We performed a prospective observational study of admissions to our semi-closed ICU over a three-month period and recorded the indications for antimicrobial therapy, agents used, duration of use, changes in therapy and reasons for changes in therapy. A change in therapy was defined as the initiation or discontinuation of an antimicrobial agent. There were 51 patients admitted during the three-month study period and all received antimicrobial therapy. There were 135 changes in antimicrobial therapy. 89 (66%) were made by the ICU team and 32 (24%) were made by the primary team. Changes were made due to a deterioration or lack of clinical response in 41 (30%) cases, due to the completion of prescribed course in 36 (27%) cases, and in response to a sensitivity result in 25 (19%) cases. Prophylactic antibiotic courses (n=24) were of a duration greater than 24 hours in 15 (63%) instances. In conclusion, the majority of changes in antimicrobial therapy were not culture-based and the duration of surgical prophylaxis was in excess of current recommended guidelines.

The effect of intestinal microbiota dysbiosis on growth and detection of carbapenemase-producing Enterobacterales within an in vitro gut model.

BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) can colonize the gut and are of major clinical concern. Identification of CPE colonization is problematic; there is no gold-standard detection method, and the effects of antibiotic exposure and microbiota dysbiosis on detection are unknown. AIM: Based on a national survey we selected four CPE screening assays in common use. We used a clinically reflective in vitro model of human gut microbiota to investigate the performance of each test to detect three different CPE strains under different, clinically relevant antibiotic exposures. METHODS: Twelve gut models were seeded with a pooled faecal slurry and exposed to CPE either before, after, concomitant with, or in the absence of piperacillin-tazobactam (358 mg/L, 3 × daily, seven days). Total Enterobacterales and CPE populations were enumerated daily. Regular screening for CPE was performed using Cepheid Xpert® Carba-R molecular test, and with Brilliance™ CRE, Colorex™ mSuperCARBA and CHROMID® CARBA SMART agars. FINDINGS: Detection of CPE when the microbiota are intact is problematic. Antibiotic exposure disrupts microbiota populations and allows CPE proliferation, increasing detection. The performances of assays varied, particularly with respect to different CPE strains. The Cepheid assay performed better than the three agar methods for detecting a low level of CPE within an intact microbiota, although performance of all screening methods was comparable when CPE populations increased in a disrupted microbiota. CONCLUSION: CPE strains differed in their dynamics of colonization in an in vitro gut model and in their subsequent response to antibiotic exposure. This affected detection by molecular and screening methods, which has implications for the sensitivity of CPE screening in healthcare settings.

Accelerated wound repair, cell proliferation, and collagen accumulation are produced by a cartilage-derived growth factor.

Cartilage-derived growth factor (CDGF), a cationic polypeptide of approximately 18,000 mol wt, was prepared from bovine articular cartilage; other sources were bovine and human scapular and costal cartilage. Previous studies have shown that CDGF stimulates the proliferation of cultured mouse fibroblasts as well as chondrocytes and endothelial cells from various sources. In this study, CDGF was shown to stimulate dose-dependently the accumulation of DNA and collagen by rat embryo fibroblasts and a population of fibroblasts derived from granulation tissue. CDGF also stimulated the proliferation of cultured bovine capillary endothelial cells dose-dependently. To evaluate the effects of CDGF in vivo, we implanted polyvinyl alcohol sponges subcutaneously in rats. 6 d postimplantation, sponges were injected with 300 micrograms of partially purified CDGF, a dose which takes into account the cell numbers in the sponges as compared with cell cultures. CDGF rapidly disappeared from the sponges and only approximately 10% of the initial dose was present at 4 h. Despite its transient presence, CDGF caused a relative increase in sponge DNA content of 2.6-fold at 48 h and 2.4-fold at 72 h. We repeated the sponge experiment by using 500-ng injections of CDGF purified to near homogeneity by heparin-Sepharose chromatography. Purified CDGF caused significant increases in sponge collagen, protein, and DNA content at 48 and 72 h after a single injection. The effects of CDGF were abolished by heat and unaffected by reduction of disulfide linkages. Morphologically, CDGF did not evoke an inflammatory response, and its effect on proliferating endothelial cells and fibroblasts was, therefore, probably direct. However, increases in DNA content of sponges could not be fully accounted for by increased DNA synthesis, which suggests that recruitment may be an important component of the in vivo response. Taken together, the effects of CDGF on cultured cells and granulation tissue suggest that the sustained presence of CDGF in vivo may greatly enhance its effects upon wound repair.

Dielectric, calorimetric and elastic anomalies associated with the first order [Formula: see text] phase transition in (Ca, Sr)TiO(3) perovskites.

Conduction calorimetry has been used to determine with high precision the latent heat and variation in heat capacity which accompany the first order [Formula: see text] phase transition in perovskites with compositions (Ca(1-x)Sr(x))TiO(3), x = 0.65, 0.68, 0.74 (CST65, CST68, CST74). In CST65 (CST68), the latent heat is dissipated/absorbed over a temperature interval of ∼11 K (∼6 K), which is centred on ∼292 K (∼258 K) during cooling and ∼302 K (∼270 K) during heating. The magnitude of the latent heat diminishes with increasing SrTiO(3) content and was not detected in CST74. Integration of the latent heat and excess heat capacity yields small excess entropies, which are consistent with the structural changes being displacive rather than order-disorder in origin. Resonant ultrasound spectroscopy measurements on the same CST65 sample as used for dielectric and calorimetric measurements through the same temperature intervals have allowed quantitative correlations to be made with the bulk modulus, shear modulus and acoustic dissipation parameter, Q(-1). The dielectric anomaly and changes in Q(-1) can be understood as being linear combinations of the properties of the separate I4/mcm and Pbcm phases in proportion to their volume fractions across the two-phase field. A change of only ∼0.5-1 GPa has been detected in the bulk modulus but the shear modulus softens by ∼5-8 GPa as the transition interval is approached from above and below. This shear mode softening presumably reflects clustering and/or phonon softening in both the I4/mcm and Pbcm structures. This pattern of structure-property relations could be typical of first order transitions in perovskites where there is no group/subgroup relationship between the high and low symmetry phases.

Infective endocarditis: a retrospective cohort study.

BACKGROUND: Infective endocarditis (IE) is a potentially life-threatening infection of the heart's endocardial surface. Despite advances in the diagnosis and management of IE, morbidity and mortality remain high. AIM: To characterize the demographics, bacteriology and outcomes of IE cases presenting to an Irish tertiary referral centre. DESIGN: Retrospective cohort study. METHODS: Patients were identified using Hospital Inpatient Enquiry and Clinical Microbiology inpatient consult data, from January 2005 to January 2014. Patients were diagnosed with IE using Modified Duke Criteria. Standard Bayesian statistics were employed for analysis and cases were compared to contemporary international registries. RESULTS: Two hundred and two patients were diagnosed with IE during this period. Mean age 54 years. Of these, 136 (67%) were native valve endocarditis (NVE), 50 (25%) were prosthetic valve endocarditis (PVE) and 22 (11%) were cardiovascular implantable electronic device-associated endocarditis. Culprit organism was identified in 176 (87.1%) cases and Staphylococcal species were the most common (57.5%). Fifty-nine per cent of NVE required surgery compared to 66% of PVE. Mean mortality rate was 17.3%, with NVE being the lowest (12.5%) and PVE the highest (32%). Increasing age was also associated with increased mortality. Fifty-three (26.2%) patients had embolic complications. CONCLUSIONS: This Irish cohort exhibited first-world demographic patterns comparable to those published in contemporary international literature. PVE required surgery more often and was associated with higher rates of mortality than NVE. Embolic complications were relatively common and represent important sequelae, especially in the intravenous drug user population. It is also pertinent to aggressively treat older cohorts as they were associated with increased mortality.