Infrared spectroscopy of solid CO-CO2 mixtures and layers

The spectra of pure, mixed and layered CO and CO2 ices have been studied systematically under laboratory conditions using infrared spectroscopy. This work provides improved resolution spectra (0.5 cm-1) of the CO2 bending and asymmetric stretching mode, as well as the CO stretching mode, extending the existing Leiden database of laboratory spectra to match the spectral resolution reached by modern telescopes and to support the interpretation of the most recent data from Spitzer. It is shown that mixed and layered CO and CO2 ices exhibit very different spectral characteristics, which depend critically on thermal annealing and can be used to distinguish between mixed, layered and thermally annealed CO-CO2 ices. CO only affects the CO2 bending mode spectra in mixed ices below 50K under the current experimental conditions, where it exhibits a single asymmetric band profile in intimate mixtures. In all other ice morphologies the CO2 bending mode shows a double peaked profile, similar to that observed for pure solid CO2. Conversely, CO2 induces a blue-shift in the peak-position of the CO stretching vibration, to a maximum of 2142 cm-1 in mixed ices, and 2140-2146 cm-1 in layered ices. As such, the CO2 bending mode puts clear constraints on the ice morphology below 50K, whereas beyond this temperature the CO2 stretching vibration can distinguish between initially mixed and layered ices. This is illustrated for the low-mass YSO HH46, where the laboratory spectra are used to analyse the observed CO and CO2 band profiles and try to constrain the formation scenarios of CO2.Comment: Accepted in A&

MicroRNAs Associated with Chronic Mucus Hypersecretion in COPD Are Involved in Fibroblast-Epithelium Crosstalk

We recently identified microRNAs (miRNAs) associated with chronic mucus hypersecretion (CMH) in chronic obstructive pulmonary disease (COPD), which were expressed in both airway epithelial cells and fibroblasts. We hypothesized that these miRNAs are involved in communication between fibroblasts and epithelium, contributing to airway remodeling and CMH in COPD. Primary bronchial epithelial cells (PBECs) differentiated at the air–liquid interface, and airway fibroblasts (PAFs) from severe COPD patients with CMH were cultured alone or together. RNA was isolated and miRNA expression assessed. miRNAs differentially expressed after co-culturing were studied functionally using overexpression with mimics in mucus-expressing human lung A549 epithelial cells or normal human lung fibroblasts. In PBECs, we observed higher miR-708-5pexpression upon co-culture with fibroblasts, and miR-708-5p expression decreased upon mucociliary differentiation. In PAFs, let-7a-5p, miR-31-5p and miR-146a-5p expression was significantly increased upon co-culture. miR-708-5p overexpression suppressed mucin 5AC (MUC5AC) secretion in A549, while let-7a-5poverexpression suppressed its target gene COL4A1 in lung fibroblasts. Our findings suggest that let-7a-5p, miR-31-5p and miR-146a-5p may be involved in CMH via fibroblasts–epithelium crosstalk, including extracellular matrix gene regulation, while airway epithelial expression of miR-708-5p may be involved directly, regulating mucin production. These findings shed light on miRNA-mediated mechanisms underlying CMH, an important symptom in COPD

Preliminary report of a gas conditioner to improve operational reliability of cryotherapy in developing countries

BACKGROUND: Cryotherapy is a safe, affordable, and effective method of treatment for cervical intraepithelial neoplasia. In some low-resource settings, environmental conditions or qualities of the refrigerant gas can lead to blockage of cryotherapy equipment, terminating treatment. A prototype of a gas conditioner to prevent operational failure was designed, built, and field tested. METHODS: The prototype conditioner device consists of an expansion chamber that filters and dries the refrigerant gas. Users in Peru and Kenya reported on their experience with the prototype conditioner. In Ghana, simulated cryotherapy procedures were used to test the effects of the prototype conditioner, as well as the commonly used "cough technique." RESULTS: Anecdotal reports from field use of the device were favorable. During simulated cryotherapy, the prevalence of blockage during freezing were 0% (0/25) with the device alone, 23.3% (7/30) with the cough technique alone, 5.9% (1/17) with both, and 55.2% (16/29) with neither (Pearson's Chi square = 26.6, df = 3, p < 0.001 (comparison amongst all groups)). CONCLUSION: This prototype design of a cryotherapy gas conditioner is a potential solution for low-resource settings that are experiencing cryotherapy device malfunction

Occupational exposure to nano-TiO2 in the life cycle steps of new depollutant mortars used in construction

The present work is focused on the measurement of workers exposure to nano-TiO2 in the life cycle steps of depollutant mortars. It has been done in the framework of the SCAFFOLD project, which aims at the management of potential risks arising from the use of manufactured nanomaterials in construction. Main findings can be summarized as follows: (1) The occupational exposure to nano- TiO2 is below 0.3 mg/m3 for all measured scenarios. The highest concentrations were measured during the cleaning task (in the nano- TiO2 manufacturing process) and during the application (spraying) of depollutant coatings on a wall. (2) It was found a high release of particles above the background in several tasks as expected due to the nature of the activities performed. The maximum concentration was measured during drilling and during adding powder materials (mean total particle concentration up to 5.591E+04 particles/cm3 and 5.69E+04 particles/cm3). However, considering data on total particle concentration released, no striking differences have been observed when tasks have been performed using conventional materials in the sector (control) and when using materials doped with nano-objects.European Commission's FP

Training general practitioners to improve evidence-based drug treatment of patients with heart failure: a cluster randomised controlled trial

AIMS: To assess whether a single training session for general practitioners (GPs) improves the evidence-based drug treatment of heart failure (HF) patients, especially of those with HF with reduced ejection fraction (HFrEF). METHODS AND RESULTS: A cluster randomised controlled trial was performed for which patients with established HF were eligible. Primary care practices (PCPs) were randomised to care-as-usual or to the intervention group in which GPs received a half-day training session on HF management. Changes in HF medication, health status, hospitalisation and survival were compared between the two groups. Fifteen PCPs with 200 HF patients were randomised to the intervention group and 15 PCPs with 198 HF patients to the control group. Mean age was 76.9 (SD 10.8) years; 52.5% were female. On average, the patients had been diagnosed with HF 3.0 (SD 3.0) years previously. In total, 204 had HFrEF and 194 HF with preserved ejection fraction (HFpEF). In participants with HFrEF, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers decreased in 6 months in both groups [5.2%; (95% confidence interval (CI) 2.0-10.0)] and 5.6% (95% CI 2.8-13.4)], respectively [baseline-corrected odds ratio (OR) 1.07 (95% CI 0.55-2.08)], while beta-blocker use increased in both groups by 5.2% (95% CI 2.0-10.0) and 1.1% (95% CI 0.2-6.3), respectively [baseline-corrected OR 0.82 (95% CI 0.42-1.61)]. For health status, hospitalisations or survival after 12-28 months there were no significant differences between the two groups, also not when separately analysed for HFrEF and HFpEF. CONCLUSION: A half-day training session for GPs does not improve drug treatment of HF in patients with established HF

Superconception in mammalian pregnancy can be detected and increases reproductive output per breeding season

The concept of superfetation, a second conception during pregnancy, has been controversial for a long time. In this paper we use an experimental approach to demonstrate that female European brown hares (Lepus europaeus) frequently develop a second pregnancy while already pregnant and thereby increase their reproductive success. After a new, successful copulation, we confirmed additional ovulations before parturition in living, late-pregnant females by detecting a second set of fresh corpora lutea using high-resolution ultrasonography. The presence of early embryonic stages in the oviduct, demonstrated by oviduct flushing, next to fully developed fetuses in the uterus is best explained by passage of semen through the late-pregnant uterus; this was confirmed by paternity analysis using microsatellite profiling. Subsequent implantation occurred after parturition. This superfetation, categorized as superconception, significantly increased litter size and permitted females to produce up to 35.4% more offspring per breeding season. It is therefore most likely an evolutionary adaptation

Pediatric medulloblastoma express immune checkpoint B7-H3

PURPOSE: Medulloblastomas (MB) are highly malignant brain tumors that predominantly occur in young infants. Immunotherapy to boost the immune system is emerging as a novel promising approach, but is often hampered by inhibitory immune checkpoints. In the present study, we have studied immune checkpoint B7-H3 expression in a tissue cohort of human pediatric MB. METHODS: Expression of B7-H3 was detected by immunohistochemistry and classified via B7-H3 staining intensity and percentage of B7-H3 positive tumor cells. Subsequently, B7-H3 protein expression was distinguished in MB molecular subtypes and correlated to immune cell infiltrates, patient characteristics, and survival. RESULTS: B7-H3 protein expression was found in 23 out of 24 (96%) human pediatric MB cases and in 17 out of 24 (71%) MB cases > 25% of tumor cells had any level of B7-H3 expression. B7-H3 protein expression was more frequent on Group-4 MB as compared with other molecular subtypes (p = 0.02). Tumors with high B7-H3 expression showed less influx of γδT cells (p = 0.002) and CD3+ T cells (p = 0.041). CONCLUSION: Immune checkpoint B7-H3 is differentially expressed by the large majority of pediatric MB. This further warrants the development of novel B7-H3-directed (immuno)therapeutic methods for children with incurable, metastatic, or chemo-resistant MB

Endothelial Surface Layer Degradation by Chronic Hyaluronidase Infusion Induces Proteinuria in Apolipoprotein E-Deficient Mice

Functional studies show that disruption of endothelial surface layer (ESL) is accompanied by enhanced sensitivity of the vasculature towards atherogenic stimuli. However, relevance of ESL disruption as causal mechanism for vascular dysfunction remains to be demonstrated. We examined if loss of ESL through enzymatic degradation would affect vascular barrier properties in an atherogenic model. Eight week old male apolipoprotein E deficient mice on Western-type diet for 10 weeks received continuous active or heat-inactivated hyaluronidase (10 U/hr, i.v.) through an osmotic minipump during 4 weeks. Blood chemistry and anatomic changes in both macrovasculature and kidneys were examined. Infusion with active hyaluronidase resulted in decreased ESL (0.32±0.22 mL) and plasma volume (1.03±0.18 mL) compared to inactivated hyaluronidase (0.52±0.29 mL and 1.28±0.08 mL, p<0.05 respectively).Active hyaluronidase increased proteinuria compared to inactive hyaluronidase (0.27±0.02 vs. 0.15±0.01 µg/µg protein/creatinin, p<0.05) without changes in glomerular morphology or development of tubulo-interstitial inflammation. Atherosclerotic lesions in the aortic branches showed increased matrix production (collagen, 32±5 vs. 18±3%; glycosaminoglycans, 11±5 vs. 0.1±0.01%, active vs. inactive hyaluronidase, p<0.05). ESL degradation in apoE deficient mice contributes to reduced increased urinary protein excretion without significant changes in renal morphology. Second, the induction of compositional changes in atherogenic plaques by hyaluronidase point towards increased plaque vulnerability. These findings support further efforts to evaluate whether ESL restoration is a valuable target to prevent (micro) vascular disease progressio