Loomisward2364

High intensity focused ultrasound (HiFU) is a cyclodestructive therapy for controlling intraocular pressure (IOP) in glaucoma. The mechanism of action is thought to be through destruction of the ciliary epithelium as well as increased uveoscleral outflow. We reviewed the change in aqueous humour dynamics parameters including aqueous humour flow rate, tonographic outflow facility (TOF) and uveoscleral outflow at 12 months.

This is a prospective observational study. Consecutive patients with open angle glaucoma (OAG) or ocular hypertension (OHT) requiring further IOP lowering were enroled in the study between August 2016 and January 2017. Patients were commenced on medication washout period prior to baseline and twelve months' visit.

Sixteen patients (OAG) in the treatment group underwent assessment at twelve months follow up. Mean age was 63.1 ± 11 years. Eleven patients were African/Caribbean and 5 were Caucasian. Nine patients were female and 7 were male. Mean post-washout IOP was reduced by 21% (28.3 ± 5.7 at baseline vs 22.4 ± 8.4 mmHg at 12 months, p = 0.04). Aqueous humour flow rate was reduced by 16% at twelve months (2.40 ± 0.6 at baseline vs 2.02 ± 0.6 µl/min at 12 months, p = 0.0493). There was no statistically significant change in the TOF (0.12 ± 0.09 at baseline vs 0.08 ± 0.05 µl/min/mmHg at 12 months, p = 0.08) or uveoscleral outflow (0.6 ± 1.3 at baseline vs 1.3 ± 0.85 µl/min at 12 months, p = 0.15).

In this study, we demonstrated that the observed IOP reduction was likely due to aqueous humour flow rate reduction. The TOF and uveoscleral outflow were not detectibly changed.

In this study, we demonstrated that the observed IOP reduction was likely due to aqueous humour flow rate reduction. The TOF and uveoscleral outflow were not detectibly changed.Recent evidence shows that the expression levels of histamine receptor H3 (Hrh3) are upregulated in several types of cancer. However, the role of Hrh3 in non-small cell lung cancer (NSCLC) has not been elucidated. In the present study, we showed that the expression levels of Hrh3 were significantly increased in NSCLC samples, and high levels of Hrh3 were associated with poor overall survival (OS) in NSCLC patients. In five human NSCLC cell lines tested, Hrh3 was significantly upregulated. In NSCLC cell lines H1975, H460, and A549, Hrh3 antagonist ciproxifan (CPX, 10-80 μM) exerted moderate and concentration-dependent inhibition on the cell growth and induced apoptosis, whereas its agonist RAMH (80 μM) reversed these effects. Furthermore, inhibition of Hrh3 by CPX or siRNA retarded the migration and invasion of NSCLC cells through inhibiting epithelial-mesenchymal transition (EMT) progression via reducing the phosphorylation of PI3K/Akt/mTOR and MEK/ERK signaling pathways. In nude mice bearing H1975 cell xenograft or A549 cell xenograft, administration of CPX (3 mg/kg every other day, intraperitoneal) significantly inhibited the tumor growth with increased E-cadherin and ZO-1 expression and decreased Fibronectin expression in tumor tissue. In conclusion, this study reveals that Hrh3 plays an important role in the growth and metastasis of NSCLC; it might be a potential therapeutic target against the lung cancer.Neutropenia is a common side effect associated with nab-paclitaxel gemcitabine (Nab-Gem) therapy. We retrospectively investigated the association between neutropenia induced by first-line Nab-Gem and survival in metastatic pancreatic carcinoma patients. Metastatic pancreatic patients treated with first-line Nab-Gem were included in this retrospective analysis. Neutropenia was categorized using the National Cancer Institute Common Toxicity Criteria scale. Outcome measures were overall survival (OS), progression-free survival (PFS) and response rate. 115 patients were analyzed. Median PFS was 7 months (95% CI 5-8) for patients with grade ≥ 3 neutropenia and 6 months (95% CI 5-6) for patients with grade  less then  3 neutropenia [p = 0.08; hazard ratio (HR 0.68)]. Median OS was 13 months (95% CI 10-18) for patients with grade ≥ 3 neutropenia and 10 months (95% CI 8-13) for patients with grade  less then  3 neutropenia (p = 0.04; HR 0.44). In multivariate analysis, the occurrence of grade ≥ 3 neutropenia showed a statistically significant association with OS (HR 0.62; 95% CI 0.09-0.86; p = 0.05). Nab-Gem-induced neutropenia is associated with longer survival in metastatic pancreatic cancer patients.Over a decade ago Polymerase δ interacting protein of 38 kDa (PDIP38) was proposed to play a role in DNA repair. Since this time, both the physiological function and subcellular location of PDIP38 has remained ambiguous and our present understanding of PDIP38 function has been hampered by a lack of detailed biochemical and structural studies. Here we show, that human PDIP38 is directed to the mitochondrion in a membrane potential dependent manner, where it resides in the matrix compartment, together with its partner protein CLPX. Our structural analysis revealed that PDIP38 is composed of two conserved domains separated by an α/β linker region. The N-terminal (YccV-like) domain of PDIP38 forms an SH3-like β-barrel, which interacts specifically with CLPX, via the adaptor docking loop within the N-terminal Zinc binding domain of CLPX. In contrast, the C-terminal (DUF525) domain forms an immunoglobin-like β-sandwich fold, which contains a highly conserved putative substrate binding pocket. Importantly, PDIP38 modulates the substrate specificity of CLPX and protects CLPX from LONM-mediated degradation, which stabilises the cellular levels of CLPX. Collectively, our findings shed new light on the mechanism and function of mitochondrial PDIP38, demonstrating that PDIP38 is a bona fide adaptor protein for the mitochondrial protease, CLPXP.The prevalence of urolithiasis in humans is increasing worldwide; however, non-surgical treatment and prevention options remain limited despite decades of investigation. Most existing laboratory animal models for urolithiasis rely on highly artificial methods of stone induction and, as a result, might not be fully applicable to the study of natural stone initiation and growth. Animal models that naturally and spontaneously form uroliths are an underused resource in the study of human stone disease and offer many potential opportunities for improving insight into stone pathogenesis. These models include domestic dogs and cats, as well as a variety of other captive and wild species, such as otters, dolphins and ferrets, that form calcium oxalate, struvite, uric acid, cystine and other stone types. Improved collaboration between urologists, basic scientists and veterinarians is warranted to further our understanding of how stones form and to consider possible new preventive and therapeutic treatment options.The immune microenvironment of tumors can play a critical role in promoting or inhibiting tumor progression depending on the context. We present evidence that tumor-associated macrophages/microglia (TAMs) can promote tumor progression in the sonic hedgehog subgroup of medulloblastoma (SHH-MB). By combining longitudinal manganese-enhanced magnetic resonance imaging (MEMRI) and immune profiling of a sporadic mouse model of SHH-MB, we found the density of TAMs is higher in the ~50% of tumors that progress to lethal disease. Furthermore, reducing regulatory T cells or eliminating B and T cells in Rag1 mutants does not alter SHH-MB tumor progression. As TAMs are a dominant immune component in tumors and are normally dependent on colony-stimulating factor 1 receptor (CSF1R), we treated mice with a CSF1R inhibitor, PLX5622. Significantly, PLX5622 reduces a subset of TAMs, prolongs mouse survival, and reduces the volume of most tumors within 4 weeks of treatment. Moreover, concomitant with a reduction in TAMs the percentage of infiltrating cytotoxic T cells is increased, indicating a change in the tumor environment. Our studies in an immunocompetent preclinical mouse model demonstrate TAMs can have a functional role in promoting SHH-MB progression. Thus, CSF1R inhibition could have therapeutic potential for a subset of SHH-MB patients.Samples of South African bituminous coals were analysed for total mercury (Hg) and Hg thermospecies concentrations using an RA-915 + Zeeman Mercury Analyser. Total mercury concentrations in samples of coals (n = 57) ranged between 10 ng g-1 and 493 ng g-1 with a mean value of 150 ± 53 ng g-1. Thermospecies of Hg were determined by monitoring Hg response as a function of sample temperature, increasing at 0.8 °C/s from ambient to 720 °C. This approach provides important information on thermal release of Hg species, as indicated by their appearance over specific temperature intervals. This permits identification of the presence of Hg thermospecies in coal and their quantification in each time (temperature) interval. It was found that 76% of tested bituminous coal samples release Hg species within low temperature intervals (20-180 °C and180-360 °C). The information generated in this study will aid in the selection of suitable coals for pre-combustion treatment that can lead to significant reduction of atmospheric Hg emission during coal combustion at power stations. This analytical approach can also be used for the creation of a system of coal classification based on the temperature of release of various Hg thermospecies.Accurate identification of distant, large, and frequent sources of emission in cities is a complex procedure due to the presence of large-sized pollutants and the existence of many land use types. This study aims to simplify and optimize the visualization mechanism of long time-series of air pollution data, particularly for urban areas, which is naturally correlated in time and spatially complicated to analyze. Also, we elaborate different sources of pollution that were hitherto undetectable using ordinary plot models by leveraging recent advances in ensemble statistical approaches. The high performing conditional bivariate probability function (CBPF) and time-series signature were integrated within the R programming environment to facilitate the study's analysis. Hourly air pollution data for the period between 2007 to 2016 is collected using four air quality stations, (ca0016, ca0058, ca0054, and ca0025), situated in highly urbanized locations that are characterized by complex land use and high pollution emBPF plot indicate that ca0058 and ca0054 enable easier detection of pollutants' sources in comparison to ca0016 and ca0025 due to being located on the edge of industrial areas. This study's CBPF technique and time series signature analysis' outcomes are promising, successfully elaborating different sources of pollution that were hitherto undetectable using ordinary plot models and thus contribute to existing air quality assessment and enhancement mechanisms.The purpose of this study was to evaluate the relationships of smoking, alcohol consumption, and obesity with thyroid cancer in Korean residents. The Korean National Health Insurance Service-Health Screening Cohort includes individuals ≥ 40 years who were assessed from 2002 to 2013. BAY 2416964 mw In total, 4977 thyroid cancer participants were matched with respect to age, sex, income, and region of residence with 19,908 controls at a ratio of 14. Crude and adjusted (for the Charlson comorbidity index, smoking status, frequency of alcohol consumption, and obesity) odds ratios (ORs) were analyzed using conditional logistic regression analyses. Additionally, 95% confidence intervals (CIs) were calculated. The adjusted OR of smoking for thyroid cancer was 0.62 (95% CI 0.54-0.72, P  less then  0.001), and that of alcohol consumption was 0.83 (95% CI 0.75-0.92, P  less then  0.001). The adjusted ORs of the BMI categories were 1.13 (95% CI 1.05-1.22, P = 0.002) for obese I, and 1.24 (95% CI 1.04-1.47, P = 0.014) for obese II. The ORs of smoking and alcohol consumption were lower, and those of overweight and obesity were higher in thyroid cancer patients than in individuals in the control group.