High performance single photon sources from photolithographically defined pillar microcavities

We demonstrate that single photons can be generated from single InAs/GaAs quantum dots in photolithographically defined pillar microcavities. Pillars with a 1.9 µm diameter cavity show a four fold enhancement in the radiative decay rate due to the Purcell effect and a photon collection efficiency into a lens of up to 10%. Measurements of the second order correlation function reveal a greater than fifty fold reduction in the multi-photon emission rate compared to a laser of the same intensity

The effect of Covid-19 on alcohol use disorder and role of universal alcohol screening in an inpatient setting: a retrospective cohort control study

AimTo assess the impact of Covid-19 on alcohol use disorders (AUD) and the role of universal alcohol screening (UAS) in an inpatient setting.MethodsRetrospective cohorts were defined as pre-pandemic and pandemic admitted to Nottingham University Hospitals (April to October; 2019 and 2020) and had alcohol assessment by AUDIT-C. AUDIT-C score was assessed against age, sex, ethnicity, admission type, speciality and primary diagnosis of mental disorders. Subgroup analysis for Covid-19 positive patients was performed.ResultsA total of 63,927 admissions (47,954 patients) were included. The pandemic period compared to pre-pandemic had fewer overall admissions (27,349 vs 36,578, P < 0.001), fewer with AUD (17.6% vs 18.4%, P = 0.008) but a higher proportion of alcohol dependents (3.7% vs 3.0%, P < 0.0001). In the pandemic those with AUD were more likely to be male (P = 0.003), white (P < 0.001), in relationship (P < 0.001), of higher socioeconomic background (P < 0.001), have alcohol-related mental disorders (P = 0.002), emergency admission (P < 0.001), medical speciality admission (P < 0.001) and shorter length of stay (P < 0.033) compared to pre-pandemic AUD. Covid-19 positive patients with concomitant AUD died at younger age (P < 0.05) than Covid-19 positive patients at low risk for AUD.ConclusionsThe pandemic changed the characteristics of inpatients with AUD. There was a higher proportion of alcohol-dependent admissions with evidence that a younger, less deprived group have been significantly impacted. UAS provides a useful tool to screen for AUD and to identify the change when facing sudden health crises

Reduced expression of monocyte CD200R is associated with enhanced proinflammatory cytokine production in sarcoidosis

In sarcoidosis, the proinflammatory cytokines interferon gamma, tumour necrosis factor and interleukin-6 are released by monocyte-derived macrophages and lymphocytes in the lungs and other affected tissues. Regulatory receptors expressed on monocytes and macrophages act to suppress cytokine production, and reduced expression of regulatory receptors may thus promote tissue inflammation. The aim of this study was to characterise the role of regulatory receptors on blood monocytes in patients with sarcoidosis. Cytokine release in response to stimulation of whole blood was measured in healthy controls and Caucasian non-smoking patients with sarcoidosis who were not taking disease modifying therapy. Expression of the regulatory molecules IL-10R, SIRP-α/β, CD47, CD200R, and CD200L was measured by flow cytometry, and functional activity was assessed using blocking antibodies. Stimulated whole blood and monocytes from patients with sarcoidosis produced more TNF and IL-6 compared with healthy controls. 52.9% of sarcoidosis patients had monocytes characterised by low expression of CD200R, compared with 11.7% of controls (p < 0.0001). Patients with low monocyte CD200R expression produced higher levels of proinflammatory cytokines. In functional studies, blocking the CD200 axis increased production of TNF and IL-6. Reduced expression of CD200R on monocytes may be a mechanism contributing to monocyte and macrophage hyper-activation in sarcoidosis

Biomarkers of disease differentiation: HCV recurrence versus acute cellular rejection

The wound-healing process induced by chronic hepatitis C virus (HCV) infection triggers liver damage characterized by fibrosis development and finally cirrhosis. Liver Transplantation (LT) is the optimal surgical treatment for HCV-cirrhotic patients at end-stage liver disease. However, acute cellular rejection (ACR) and HCV recurrence disease represent two devastating complications post-LT. The accurate differential diagnosis between both conditions is critical for treatment choice, and similar histological features represent a challenge for pathologists. Moreover, the HCV recurrence disease severity is highly variable post-LT. HCV recurrence disease progression is characterized by an accelerated fibrogenesis process, and almost 30% of those patients develop cirrhosis at 5-years of follow-up. Whole-genome gene expression (WGE) analyses through well-defined oligonucleotide microarray platforms represent a powerful tool for the molecular characterization of biological process. In the present manuscript, the utility of microarray technology is applied for the ACR and HCV-recurrence biological characterization in post-LT liver biopsy samples. Moreover, WGE analysis was performed to identify predictive biomarkers of HCV recurrence severity in formalin-fixed paraffin-embedded liver biopsies prospectively collected

The Interaction between Regulatory T Cells and NKT Cells in the Liver: A CD1d Bridge Links Innate and Adaptive Immunity

Regulatory T cells (Tregs) and natural killer T (NKT) cells are two distinct lymphocyte subsets that independently regulate hepatic adaptive and innate immunity, respectively. In the current study, we examine the interaction between Tregs and NKT cells to understand the mechanisms of cross immune regulation by these cells.The frequency and function of Tregs were evaluated in wild type and NKT cell deficient (CD1dko) mice. In vitro lymphocyte proliferation and apoptosis assays were performed with NKT cells co-cultured with Tregs. The ability of Tregs to inhibit NKT cells in vivo was examined by adoptive transfer of Tregs in a model of NKT cell mediated hepatitis.CD1dko mice have a significant reduction in hepatic Tregs. Although, the Tregs from CD1dko mice remain functional and can suppress conventional T cells, their ability to suppress activation induced NKT cell proliferation and to promote NKT cell apoptosis is greatly diminished. These effects are CD1d dependent and require cell to cell contact. Adoptive transfer of Tregs inhibits NKT cell-mediated liver injury.NKT cells promote Tregs, and Tregs inhibit NKT cells in a CD1d dependent manner requiring cell to cell contact. These cross-talk immune regulations provide a linkage between innate and adaptive immunity

The polycomb group proteins, BMI-1 and EZH2, are tumour-associated antigens

We used SEREX technology to identify novel tumour-associated antigens in patients with primary hepatocellular carcinoma and found serological responses to the polycomb group (PcG) protein BMI-1, which is overexpressed in a range of different tumour types. Further studies identified T-cell responses to both BMI-1 and another PcG protein, EZH2, in cancer patients and at relatively lower levels in some normal donors. We next identified several CD8+ T-cell epitopes derived from BMI-1 and EZH2 and demonstrated that EZH2-derived peptides elicited more significant interferon-γ (IFN-γ) release than BMI-1-derived peptides. That CD8+ T cells were responsible for the observed responses was confirmed for EZH2 by both IFN-γ capture assays and tetramer staining using an HLA-A0201-restricted, EZH2-derived YMSCSFLFNL (aa 666–674) epitope. The ability of YMSCSFLFNL (aa 666–674) to stimulate the in vitro expansion of specific T cells from peripheral blood lymphocytes was greatly enhanced when the CD25+ T-cell population was depleted. EZH2-specific cytotoxic T lymphocyte clones specific for two HLA-A0201 epitopes were generated and found to recognise endogenously processed EZH2 in both HLA-matched fibroblasts and tumour cell lines. Given the widespread overexpression of PcG proteins in cancer and their critical role in oncogenesis, these data suggest that they may be useful targets for cancer immunotherapy

Highly Divergent Mitochondrial ATP Synthase Complexes in Tetrahymena thermophila

Tetrahymena ATP synthase, an evolutionarily divergent protein complex, has a very unusual structure and protein composition including a unique Fo subunit a and at least 13 proteins with no orthologs outside of the ciliate lineage

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

The evaluation of risk for obstructive sleep apnea in patients with type 2 diabetes

Cilj istraživanja je procijeniti rizik za opstrukcijsku apneju tijekom spavanja (engl. Obstructive sleep apnea, OSA) u bolesnika sa šećernom bolešću tipa 2, s pomoću STOP upitnika (engl. Snoring, Tiredness, Observed, Pressure; STOP). S pomoću Epworthove ljestvice pospanosti (ESS) procijenjena je prekomjerna dnevna pospanost i ispitana povezanost pospanosti i rizika za OSA-u u bolesnika sa šećernom bolešću tipa 2. Dosadašnja istraživanja pokazala su da oštećena tolerancije glukoze i šećerna bolest tipa 2 predstavljaju čimbenik rizika za OSA-u, ali i da OSA predstavlja čimbenik rizika za šećernu bolest tipa 2. U našem istraživanju sudjelovala su 252 ispitanika sa šećernom bolešću tipa 2, koji su bili anketirani za vrijeme redovitih pregleda u Kliničkom bolničkom centru Split. Rezultati našeg istraživanja pokazali su da je 156 ispitanika (61,9%) imalo povećan rizik za OSA-u prema rezultatima STOP upitnika. Nadalje, ispitanici koji su imali povećani rizik u odnosu na ispitanike koji nisu imali rizik za OSA-u bili su stariji (65 vs. 61 godina, p < 0,05), imali viši indeks tjelesne mase (28,6 ± 5,1 vs. 26,5 ± 4,1, p < 0,001), veći opseg vrata (41,5 ± 4,7 vs. 39,6 ± 6,2, p < 0,009) i bili pospaniji prema rezultatima ESS (5,3 ± 3,1 vs. 3,9 ± 2,5, p < 0,001). Uz šećernu bolest, većina ispitanika imala je i pridružene bolesti: arterijska hipertenzija (46%), gastroezofagealna refluksna bolest (28%), depresija (10%) i astma (8%). OSA je dio širokoga spektra poremećaja disanja tijekom spavanja koja se dovodi u vezu s metaboličkim poremećajima poput šećerne bolesti tipa 2, a epidemiološki podaci o zastupljenosti OSA u Hrvatskoj su nedostatni. Ovo istraživanje ukazuje na potrebu provođenja probira za OSA u bolesnika sa šećernom bolešću tipa 2, koristeći STOP upitnik.The aim of this study was to evaluate the risk for obstructive sleep apnea (OSA) in patients with type 2 diabetes using the STOP questionnaire (Snoring, Tiredness, Observed, Pressure; STOP). Excessive daytime sleepiness was evaluated with the Epworth sleepiness scale (ESS). Previous studies support the idea that glucose intolerance and type 2 diabetes might represent risk factors for OSA, as well as the idea of OSA being the risk factor for type 2 diabetes. A total of 252 patients with type 2 diabetes were surveyed during the regular follow-up in the Regional Centre for Diabetes, Endocrinology and Metabolic Diseases of Split University Hospital. The results of our study indicate that 156 patients (61.9%) had increased risk for OSA according to STOP questionnaire score. In addition, those at high risk for OSA were older (65 vs. 61 years of age, p < 0.05), had higher body mass index (BMI, 28.6 ± 5.1 vs. 26.5 ± 4.1, p < 0.001), higher neck circumference (41.5 ± 4.7 vs. 39.6 ± 6.2, p < 0.009), and had excessive daytime sleepiness according to the ESS score (5.3 ± 3.1 vs. 3.9 ± 2.5, p < 0.001). Individuals with type 2 diabetes reported to have comorbidities, mainly hypertension (46%), gastroesophageal reflux disease (28%), depression (10%), and asthma (8%). Based on current evidence from literature, OSA could be related to clinical conditions such as diabetes and essential hypertension. More epidemiological data are needed to establish the prevalence of OSA in Croatian patients with type 2 diabetes. Our findings indicate the relevance of STOP questionnaire use as a screening tool for obstructive sleep apnea in patients with type 2 diabetes in Croatia