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ObjectivesTo examine if therapeutic hypothermia reduces the composite outcome of death, moderate or severe disability at 18 months or more after mild neonatal encephalopathy (NE).Data sourceMEDLINE, Cochrane database, Scopus and ISI Web of Knowledge databases, using ‘hypoxic ischaemic encephalopathy’, ‘newborn’ and ‘hypothermia’, and ‘clinical trials’ as medical subject headings and terms. Manual search of the reference lists of all eligible articles and major review articles and additional data from the corresponding authors of selected articles.Study selectionRandomised and quasirandomised controlled trials comparing therapeutic hypothermia with usual care.Data extractionSafety and efficacy data extracted independently by two reviewers and analysed.ResultsWe included the data on 117 babies with mild NE inadvertently recruited to five cooling trials (two whole-body cooling and three selective head cooling) of moderate and severe NE, in the meta-analysis. Adverse outcomes occurred in 11/56 (19.6%) of the cooled babies and 12/61 (19.7%) of the usual care babies (risk ratio 1.11 (95% CIs 0.55 to 2.25)).ConclusionsCurrent evidence is insufficient to recommend routine therapeutic hypothermia for babies with mild encephalopathy and significant benefits or harm cannot be excluded.

Umbilical venous catheters are widely used in neonatal practice, therefore promoting safe use of such catheters to reduce complications remains a healthcare priority. This report will equip the reader with essential knowledge for successful catheter insertion and maintenance, which is key to better outcomes. Recent advances in safe localisation of catheter tip and the development of a red flag system will enhance the clinician’s ability to predict potential complications related to these catheters as they remain in situ.

ObjectiveTo examine the effect of therapeutic hypothermia on MR biomarkers and neurodevelopmental outcomes in babies with mild hypoxic-ischaemic encephalopathy (HIE).DesignNon-randomised cohort study.SettingEight tertiary neonatal units in the UK and the USA.Patients47 babies with mild HIE on NICHD neurological examination performed within 6 hours after birth.InterventionsWhole-body cooling for 72 hours (n=32) or usual care (n=15; of these 5 were cooled for <12 hours).Main outcome measuresMRI and MR spectroscopy (MRS) within 2 weeks after birth, and a neurodevelopmental outcome assessment at 2 years.ResultsThe baseline characteristics in both groups were similar except for lower 10 min Apgar scores (p=0.02) in the cooled babies. Despite this, the mean (SD) thalamic NAA/Cr (1.4 (0.1) vs 1.6 (0.2); p<0.001) and NAA/Cho (0.67 (0.08) vs 0.89 (0.11); p<0.001) ratios from MRS were significantly higher in the cooled group. Cooled babies had lower white matter injury scores than non-cooled babies (p=0.02). Four (27%) non-cooled babies with mild HIE developed seizures after 6 hours of age, while none of the cooled babies developed seizures (p=0.008). Neurodevelopmental outcomes at 2 years were available in 40 (85%) of the babies. Adverse outcomes were seen in 2 (14.3%) non-cooled babies, and none of the cooled babies (p=0.09).ConclusionsTherapeutic hypothermia may have a neuroprotective effect in babies with mild HIE, as demonstrated by improved MRS biomarkers and reduced white matter injury on MRI. This may warrant further evaluation in adequately powered randomised controlled trials.

Bone loss is a significant clinical problem, and treatments utilizing donated graft material are limited. To meet future demands in the healthcare industry, there has been a shift of outlook toward the use of bioactive materials for tissue regeneration. A number of in vivo and in vitro studies have highlighted the potential of the bioactive glass ceramic 45S5 Bioglass as a synthetic regenerative scaffold. The application of sol-gel processing techniques has led to the synthesis of mesoporous bioactive glasses with greater textural and compositional variety. In this study, we evaluated the effects of supplemented tissue culture medium containing up to 203 ppm silica prepared by static soaking of particles of 58S sol-gel bioactive glass (58% SiO 2 , 33% CaO, 9% P 2 O 5 ) on the in vitro proliferation and differentiation of murine and human primary osteoblasts. These extracts had a higher silica content than those used previously in studies of 45S5 Bioglass, because of the faster rates of ion exchange permitted by the higher surface area-to-volume ratio of mesoporous glass. We found that osteoblasts from both species increased their proliferation in response to the glass-conditioned medium. In addition, the extent to which supplemented medium could alter cell differentiation varied with time in culture. Proliferation induced by supplemented medium paralleled effects induced by treatment with basic fibroblast growth factor, a known mitogenic growth factor for osteoblasts. Bone nodule formation was also increased by exposure to the glass-conditioned medium and this effect was positively correlated with the dose of glass used to prepare the medium. Apoptosis was stimulated by glass-conditioned medium in murine osteoblasts, but inhibited in human osteoblasts. These data demonstrate the bioactive effects of dissolution products derived from sol-gel materials on primary osteoblasts and complements in vivo studies that indicate the suitability of this material as a bone graft substitute.

Embryonic stem (ES) cells represent a potentially useful cell source for tissue regeneration. Previously, using factors known to enhance differentiation and mineralization of primary osteoblasts, we were able to generate cell populations enriched with osteoblasts from a murine ES cell source. Dexamethasone was a potent inducer of osteoblast differentiation and the timing of stimulation markedly increased the proportion of osteoblast lineage cells. This study examined whether inorganic stimuli derived from bioactive glasses could affect the differentiation of osteoblasts in an ES-cell based system. Previous work has demonstrated the ability of soluble ions released from bioactive glasses undergoing dissolution in vitro to stimulate gene expression characteristic of a mature phenotype in primary osteoblasts. We report here on the potential of soluble extracts prepared from 58S sol-gel bioactive glass to further enhance lineage-specific differentiation in murine ES cells. Differentiation of ES cells into osteogenic cells was characterized by the formation of multilayered, mineralized nodules. These nodules contained cells expressing the transcription factor runx2/cbfa-1, and deposition of osteocalcin in the extracellular matrix was detected by immunostaining. When differentiating cells were placed in an osteoblast maintenance medium supplemented with soluble extracts prepared from bioactive glass powders, we observed increased formation of mineralized nodules (98 ± 6%, mean ± SEM) and alkaline phosphatase activity (56 ± 14%, mean ± SEM) in a pattern characteristic of osteoblast differentiation. This effect of the glass extracts exhibited dose dependency, with alkaline phosphatase activity and nodule formation increasing with extract concentrations. Compared with medium supplemented with dexamethasone, which had previously been used to enhance osteoblast lineage derivation, the glass extracts were as effective at inducing formation of mineralized nodules by murine ES cells. When glass extracts were used in combination with dexamethasone, a further increase in the number of nodules was observed (110 ± 16%; cf. 83 ± 7% for dexamethasone alone). This study demonstrates the capacity of an entirely inorganic material to stimulate differentiation of ES cells toward a lineage with therapeutic potential in tissue-engineering applications.

Bone loss is a significant clinical problem, and treatments utilizing donated graft material are limited. To meet future demands in the healthcare industry, there has been a shift of outlook toward the use of bioactive materials for tissue regeneration. A number of in vivo and in vitro studies have highlighted the potential of the bioactive glass ceramic 45S5 Bioglass as a synthetic regenerative scaffold. The application of sol-gel processing techniques has led to the synthesis of mesoporous bioactive glasses with greater textural and compositional variety. In this study, we evaluated the effects of supplemented tissue culture medium containing up to 203 ppm silica prepared by static soaking of particles of 58S sol-gel bioactive glass (58% SiO(2), 33% CaO, 9% P(2)O(5)) on the in vitro proliferation and differentiation of murine and human primary osteoblasts. These extracts had a higher silica content than those used previously in studies of 45S5 Bioglass, because of the faster rates of ion exchange permitted by the higher surface area-to-volume ratio of mesoporous glass. We found that osteoblasts from both species increased their proliferation in response to the glass-conditioned medium. In addition, the extent to which supplemented medium could alter cell differentiation varied with time in culture. Proliferation induced by supplemented medium paralleled effects induced by treatment with basic fibroblast growth factor, a known mitogenic growth factor for osteoblasts. Bone nodule formation was also increased by exposure to the glass-conditioned medium and this effect was positively correlated with the dose of glass used to prepare the medium. Apoptosis was stimulated by glass-conditioned medium in murine osteoblasts, but inhibited in human osteoblasts. These data demonstrate the bioactive effects of dissolution products derived from sol-gel materials on primary osteoblasts and complements in vivo studies that indicate the suitability of this material as a bone graft substitute.

Introduction and objectivesCT pulmonary angiography (CTPA) is recommended as the investigation of choice for suspected pulmonary embolism (PE). Even in appropriately risk-assessed groups, CTPA often proves negative for PE, but additional diagnostic information is still provided by technically adequate scans. We reviewed our CTPAs to assess technical quality and final diagnosis.MethodsRetrospective review of CTPAs performed in 2013 in a 588 bed district general hospital. All patients selected were considered either intermediate or high probability for PE based on Wells PE clinical risk scoring. Only imaging performed on patients presenting as acute admissions was reviewed. Patients under the age of 16 were excluded, but no upper age limit was applied in order to be fully representative of our patient population and clinical practice. Scans were assessed for their diagnostic and technical quality by the reporting radiologist.Results720 CTPAs were selected for review. Patient mean age 66.4 (range 17–103). PE was demonstrated in 135 studies (18.8%). 111 CTPAs (15%) excluded PE and were otherwise normal. 355 CTPA (49%) excluded PE but revealed an alternative diagnosis. Of these, cardiac failure (26%), emphysema (19%), pneumonia (16%), interstitial lung disease (10%), bronchiectasis (9%) and pleural disease (8%) were the most frequently reported clinically significant diagnoses. 119 CTPAs were considered technically inadequate to exclude PE based on insufficient contrast opacification, however an alternative explanatory diagnosis was seen in 76 (64%) of these. In the remaining 43 cases no diagnosis was reported, and only 2 patients had repeat CTPA performed during the same admission. Four patients from the non-diagnostic group represented within a 3 month follow up period and were subsequently proven to have PE on repeat CTPA.ConclusionsCTPA can provide an alternative diagnosis in the majority of cases even if PE is excluded. Of these, cardiac failure and emphysema were the most common diagnoses. Physicians must be vigilant for non-diagnostic scans and arrange further tests as appropriate, as in our series 4/43 patients with technically inadequate imaging on initial presentation subsequently represented with PE.

Purpose>The purpose of this study is to detail the experiences, perspectives and emerging framework for the delivery of library services by member libraries of the College Libraries Information Network (COLINET) at the onset and during the COVID-19 pandemic in Jamaica.Design/methodology/approach>An exploratory sequential mixed approach was used for this study. Qualitative data was collected initially using a semi-structured interview with a virtual focus group comprising seven librarians from the COLINET in Jamaica. Purposive sampling was used to select the participants for the focus group. The second phase of data collection used an online survey through Google Forms to the membership of COLINET; 19 of 31 libraries (61.2%) responded to the survey.Findings>The findings reveal the current status of library operation and service delivery at the COLINET member libraries. The impact of COVID-19 on staffing arrangements, support and engagement, library resources and services are seen through the lens of the challenges and opportunities presented by the pandemic.Research limitations/implications>In total, 19 of the 31 libraries in COLINET responded to the survey; therefore, the researchers were unable to get a comprehensive assessment of the impact of COVID-19 on COLINET libraries.Practical implications>This study will assist libraries in their response to COVID-19 and other similar future national public health crises. The findings and recommendations can provide a blueprint for developing policies and procedures for libraries during a national health crisis. Additionally, it will add to the empirical literature on Caribbean libraries.Originality/value>This study is essential for libraries responding to the coronavirus pandemic in Jamaica and the wider Caribbean region. This study examines the response of academic libraries from diverse tertiary institutions; exploring their challenges, solutions and emerging frameworks; making it representative and inclusive for academic libraries. This study advances the limited research that exists with regard to Caribbean libraries and the COVID-19 pandemic.

The success of Mycobacterium species as pathogens depends on their ability to maintain an infection inside the phagocytic vacuole of the macrophage. Although the bacteria are reported to modulate maturation of their intracellular vacuoles, the nature of such modifications is unknown. In this study, vacuoles formed around Mycobacterium avium failed to acidify below pH 6.3 to 6.5. Immunoelectron microscopy of infected macrophages and immunoblotting of isolated phagosomes showed that Mycobacterium vacuoles acquire the lysosomal membrane protein LAMP-1, but not the vesicular proton-adenosine triphosphatase (ATPase) responsible for phagosomal acidification. This suggests either a selective inhibition of fusion with proton-ATPase-containing vesicles or a rapid removal of the complex from Mycobacterium phagosomes.