A priori study of subgrid-scale features in turbulent Rayleigh-Bénard convection

At the crossroad between flow topology analysis and turbulence modeling, a priori studies are a reliable tool to understand the underlying physics of the subgrid-scale (SGS) motions in turbulent flows. In this paper, properties of the SGS features in the framework of a large-eddy simulation are studied for a turbulent Rayleigh-Bénard convection (RBC). To do so, data from direct numerical simulation (DNS) of a turbulent air-filled RBC in a rectangular cavity of aspect ratio unity and p spanwise open-ended distance are used at two Rayleigh numbers Ra € (108, 1010) [Dabbagh et al.,Peer ReviewedPostprint (author's final draft

Regenerative function of immune system: Modulation of muscle stem cells

Ageing is characterised by progressive deterioration of physiological systems and the loss of skeletal muscle mass is one of the most recognisable, leading to muscle weakness and mobility impairments. This review highlights interactions between the immune system and skeletal muscle stem cells (widely termed satellite cells or myoblasts) to influence satellite cell behaviour during muscle regeneration after injury, and outlines deficits associated with ageing. Resident neutrophils and macrophages in skeletal muscle become activated when muscle fibres are damaged via stimuli (e.g. contusions, strains, avulsions, hyperextensions, ruptures) and release high concentrations of cytokines, chemokines and growth factors into the microenvironment. These localised responses serve to attract additional immune cells which can reach in excess of 1 × 105 immune cell/mm3 of skeletal muscle in order to orchestrate the repair process. T-cells have a delayed response, reaching peak activation roughly 4 days after the initial damage. The cytokines and growth factors released by activated T-cells play a key role in muscle satellite cell proliferation and migration, although the precise mechanisms of these interactions remain unclear. T-cells in older people display limited ability to activate satellite cell proliferation and migration which is likely to contribute to insufficient muscle repair and, consequently, muscle wasting and weakness. If the factors released by T-cells to activate satellite cells can be identified, it may be possible to develop therapeutic agents to enhance muscle regeneration and reduce the impact of muscle wasting during ageing and disease

Treatment outcomes for children with multidrug-resistant tuberculosis: a systematic review and meta-analysis

BACKGROUND: Paediatric multidrug-resistant (MDR) tuberculosis is a public health challenge of growing concern, accounting for an estimated 15% of all global cases of MDR tuberculosis. Clinical management is especially challenging, and recommendations are based on restricted evidence. We aimed to assess existing evidence for the treatment of MDR tuberculosis in children. METHODS: We did a systematic review and meta-analysis of published and unpublished studies reporting treatment outcomes for children with MDR tuberculosis. We searched PubMed, Ovid, Embase, Cochrane Library, PsychINFO, and BioMedCentral databases up to Oct 31, 2011. Eligible studies included five or more children (aged ≤16 years) with MDR tuberculosis within a defined treatment cohort. The primary outcome was treatment success, defined as a composite of cure and treatment completion. RESULTS: We identified eight studies, which reported treatment outcomes for a total of 315 patients. We recorded much variation in the characteristics of patients and programmes. Time to appropriate treatment varied from 2 days to 46 months. Average duration of treatment ranged from 6 months to 34 months, and duration of follow-up ranged from 12 months to 37 months. The pooled estimate for treatment success was 81·67% (95% CI 72·54-90·80). Across all studies, 5·9% (95% CI 1·3-10·5) died, 6·2% (2·3-10·2) defaulted, and 39·1% (28·7-49·4) had an adverse event. The most common drug-related adverse events were nausea and vomiting. Other serious adverse events were hearing loss, psychiatric effects, and hypothyroidism. INTERPRETATION: The treatment of paediatric MDR tuberculosis has been neglected, but when children are treated outcomes can be achieved that are at least as good as those reported for adults. Programmes should be encouraged to report outcomes in children to improve the knowledge base for care, especially as new drugs become available. FUNDING: None

IL-22 mediates goblet cell hyperplasia and worm expulsion in intestinal helminth infection.

Type 2 immune responses are essential in protection against intestinal helminth infections. In this study we show that IL-22, a cytokine important in defence against bacterial infections in the intestinal tract, is also a critical mediator of anti-helminth immunity. After infection with Nippostrongylus brasiliensis, a rodent hookworm, IL-22-deficient mice showed impaired worm expulsion despite normal levels of type 2 cytokine production. The impaired worm expulsion correlated with reduced goblet cell hyperplasia and reduced expression of goblet cell markers. We further confirmed our findings in a second nematode model, the murine whipworm Trichuris muris. T.muris infected IL-22-deficient mice had a similar phenotype to that seen in N.brasiliensis infection, with impaired worm expulsion and reduced goblet cell hyperplasia. Ex vivo and in vitro analysis demonstrated that IL-22 is able to directly induce the expression of several goblet cell markers, including mucins. Taken together, our findings reveal that IL-22 plays an important role in goblet cell activation, and thus, a key role in anti-helminth immunity

Reconciliation or Alienation: The Representation of the Syrian Refugee Crisis in the Jordanian Print Media: Al-Ghad Newspaper as a Case Study

The influx of Syrian refugees to Jordan is considered one of the most serious social events that the country has witnessed in decades. The unprecedented flow of refugees that received extensive coverage by the Jordanian print media played an instrumental role in shaping the representation of both the event and the actors involved in the crisis. This paper departs from the premise that news reports are “elements of social events” and as such employ language to change, maintain or inculcate the knowledge, beliefs and social relations shared by members of a society. To this end, Critical Discourse Analysis (CDA) is adopted to investigate how Al-Ghad Newspaper uses language to represent and frame the Syrian refugee crisis and the Syrian refugees and considers whether this portrayal has contributed to the reconciliation or alienation of the Syrian refugees in the Jordanian society

The effect of lymphocytes secretome on skeletal muscle stem cells regeneration with ageing

Older people experience skeletal muscle wasting, in part due to impaired proliferative capacity of quiescent skeletal muscle satellite cells and. The work presented in this thesis set out to examine the hypothesis that microenvironment of skeletal muscles can be influenced by immune cell secretions, which affect satellite cell proliferation, and that beneficial immune-muscle interactions in young people are blunted in elderly. The aim of this research was to investigate the role of ageing human lymphocytes on skeletal muscle cell behaviour. For this purpose, lymphocytes were isolated from whole blood of young (aged 18-25 years) and older (aged 78-85 years) healthy volunteers and older healthy volunteers. All the participants were healthy, with no history of muscle disease and not on immunosuppressant or corticosteroids treatment that affect immune function. Lymphocytes were cultured with, or without, anti-CD3/CD28 activators for 4 days to induce release of cytokines, interleukins and growth factors into the media. The secreted proteins were used to prepare conditioned media that were used to culture C2C12 myoblasts. Secretomes were analysed and fifteen secreted Th1/Th2 cytokines and IGF-I were quantified by multiplex immunoassay. The gene expression and protein concentrations of amphiregulin were determined from T-lymphocytes lysates by real-time PCR and ELISA respectively. The levels of CD25 and FoxP3 expression in lymphocytes were examined using flow cytometry. The expression of muscle transcription factors, MyoD and Myogenin were determined by real- time PCR. Activated Mek1/Erk1/2 and Akt/mTOR were measured by multiplex immunoassay. Our results demonstrate for the first time that a decrease in the levels of amphiregulin and CD25 coincides with the increase in FoxP3 with ageing, which may be involved in suppression of lymphocytes. Seven cytokines were differentially secreted by the young- compared with the old-activated lymphocytes. The secretome from young-activated lymphocytes had 30% (P<0.005) higher IGF-I concentrations compared with old and control treatments. The conditioned media from young -activated lymphocytes increased the rate of proliferation of myoblasts by ~3-fold (P<0.005) and caused an approximate 4-fold (P<0.005) increase in migration compared with non-activated lymphocyte control media. These responses were characterised the extended proliferation of young -treated myoblasts was also associated with a decrease in MyoD and Myogenin and an increase in mediators of proliferation Mek1/Erk1/2and a decrease in the key proteins for differentiation, Akt/mTOR. In contrast, myoblasts treated with conditioned media from old-activated lymphocytes exhibited a high degree of differentiation

Deep learning-enabled technologies for bioimage analysis.

Deep learning (DL) is a subfield of machine learning (ML), which has recently demonstrated its potency to significantly improve the quantification and classification workflows in biomedical and clinical applications. Among the end applications profoundly benefitting from DL, cellular morphology quantification is one of the pioneers. Here, we first briefly explain fundamental concepts in DL and then we review some of the emerging DL-enabled applications in cell morphology quantification in the fields of embryology, point-of-care ovulation testing, as a predictive tool for fetal heart pregnancy, cancer diagnostics via classification of cancer histology images, autosomal polycystic kidney disease, and chronic kidney diseases

Regenerative endodontics: a true paradigm shift or a bandwagon about to be derailed?

Aims: Regenerative endodontic techniques (RETs) have been hailed as a paradigm shift for the management of traumatised non-vital immature permanent anterior teeth. In this article the aim was to critically appraise the literature with regards to the outcome of regenerative endodontics on root development. Methods: Critical review of the literature where regenerative endodontic techniques have been used in the management of immature non-vital teeth with continuation of root development as the main outcome reported. Results: Most studies published were in the form of case reports and series with very few randomised controlled trials with a high risk of bias. Continuation of root development following the use of RET has been shown to be unpredictable at best with lower success in those teeth losing vitality as a result of dental trauma. Conclusions: Despite the high success of regenerative endodontics in terms of periodontal healing including resolution of clinical and radiographic signs and symptoms of infection, continuation of root development remains an unpredictable outcome. The use of a blood clot as a scaffold in regenerative endodontics should be reviewed carefully as that might offer an environment for repair rather than regeneration. In addition, preservation of structures, such as Hertwig’s epithelial root sheath, may have an important bearing on the success of this approach and should be further investigated

Cysteamine inhibits lysosomal oxidation of low density lipoprotein in human macrophages and reduces atherosclerosis in mice

Background and aims: We have shown previously that low density lipoprotein (LDL) aggregated by vortexing is internalised by macrophages and oxidised by iron in lysosomes to form the advanced lipid/protein oxidation product ceroid. We have now used sphingomyelinase-aggregated LDL, a more pathophysiological form of aggregated LDL, to study lysosomal oxidation of LDL and its inhibition by antioxidants, including cysteamine (2-aminoethanethiol) which concentrates in lysosomes by several orders of magnitude. We have also investigated the effect of cysteamine on atherosclerosis in mice. Methods: LDL was incubated with sphingomyelinase, which increased its average particle diameter from 26 to 170 nm, and was then incubated for up to 7 days with human monocyte-derived macrophages. LDL receptor-deficient mice were fed a Western diet (19-22 per group) and some given cysteamine in their drinking water at a dose equivalent to that used in cystinosis patients. The extent of atherosclerosis in the aortic root and the rest of the aorta was measured. Results: Confocal microscopy revealed lipid accumulation in lysosomes in the cultured macrophages. Large amounts of ceroid were produced, which colocalised with the lysosomal marker LAMP2. The antioxidants cysteamine, butylated hydroxytoluene, amifostine and its active metabolite WR-1065, inhibited the production of ceroid. Cysteamine at concentrations well below those expected to be present in lysosomes inhibited the oxidation of LDL by iron ions at lysosomal pH (pH 4.5) for prolonged periods. Finally, we showed that the extent of atherosclerotic lesions in the aortic root and arch of mice was significantly reduced by cysteamine. Conclusions: These results support our hypothesis that lysosomal oxidation of LDL is important in atherosclerosis and hence antioxidant drugs that concentrate in lysosomes might provide a novel therapy for this disease