Морфология и трехмерные изображения рудника-пещеры Кан-и-Гут

Путём сравнительного анализа и компьютерной обработки данных чертежей и схем из разных источников впервые получена пространственная (3D) модель одного из самых сложных в морфологическом отношении подземелий смешанного типа – рудника-пещеры Кан-и-Гут (Кыргызстан). Описана методика перевода графических данных в цифровой формат. Найдены основные морфометрические параметры полости, представлены трехмерные изображения основных его отделов, обсуждается их морфология. В ряде полостей рудника-пещеры выявлены существенные изменения, произошедшие за последние 50 лет вследствие масштабных обрушений.Шляхом порівняльного аналізу і комп’ютерної обробки даних креслень і схем з різних джерел вперше отримана просторова (3d) модель одного з найскладніших в морфологічному відношенні підземель змішаного типа – копальні-печери Кан-і-Гут (Киргизстан). Описана методика переведення графічних даних в цифровий формат. Знайдені основні морфометричні параметри порожнини, представлені тривимірні зображення основних його відділів, обговорюється їх морфологія. У ряді порожнин копальні-печери виявлені істотні зміни, події за останніх 50 років унаслідок масштабних обвалень.Kan-i-Gut mined cave, located in Kyrgyzstan, is one of the most morphologically complex cavities of mixed genesis. For the first time, a 3D model was developed for this cave by comparative analyses and computer processing of cave maps and mine surveyor plan and profile, obtained from different sources. The methodology of transferring graphical data into digital format is described. Primary morphometric parameters of the mined cave are gathered, and 3D images of its main parts are presented. Essential morphological changes due to vast collapses during the last 50 years were discovered

Has the Rate of CD4 Cell Count Decline before Initiation of Antiretroviral Therapy Changed over the Course of the Dutch HIV Epidemic among MSM?

Introduction:Studies suggest that the HIV-1 epidemic in the Netherlands may have become more virulent, leading to faster disease progression if untreated. Analysis of CD4 cell count decline before antiretroviral therapy (ART) initiation, a surrogate marker for disease progression, may be hampered by informative censoring as ART initiation is more likely with a steeper CD4 cell count decline.Methods:Development of CD4 cell count from 9 to 48 months after seroconversion was analyzed using a mixed-effects model and 2 models that jointly modeled CD4 cell counts and time to censoring event (start ART

Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC

Cryptococcus neoformans and neutrophil migration

This thesis has focused on several aspects of cryptococcal glucuronoxylomannan (GXM)-related interference with neutrophil migration into inflammatory sites. First, the effect of GXM on neutrophil adhesion (rolling and firm adhesion) to the endothelium was investigated and potential mechanisms were explored. Second, we investigated the outcome of GXM treatment on neutrophil recruitment in a model of myocardial ischemia. Finally, we examined the role of certain structural elements of GXM in the effects on neutrophil migration

Cryptococcus neoformans and neutrophil migration

This thesis has focused on several aspects of cryptococcal glucuronoxylomannan (GXM)-related interference with neutrophil migration into inflammatory sites. First, the effect of GXM on neutrophil adhesion (rolling and firm adhesion) to the endothelium was investigated and potential mechanisms were explored. Second, we investigated the outcome of GXM treatment on neutrophil recruitment in a model of myocardial ischemia. Finally, we examined the role of certain structural elements of GXM in the effects on neutrophil migration

Use of recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin in elderly patients

Aim: Data on the real-world use of hyaluronidase-facilitated subcutaneous 10% immunoglobulin (fSCIG; HyQvia (R)) in elderly patients with primary or secondary immunodeficiencies (PID or SID) are unreported. This study determined real-world patterns from one administration of fSCIG. Materials & methods: In this retrospective, multicenter study, medical records of patients aged >= 65 years with PID or SID were reviewed. Results: The majority of patients (mean age: 69.9 years) with PID (n = 10) or SID (n = 6) self-administered fSCIG (200-350 ml) at home every 3-4 weeks using a single infusion site by infusion pump at rates up to 300 ml/h. Conclusion: This study provides initial real-world evidence supporting home-based, self-administration of large volumes of fSCIG in elderly patients with PID or SID.Lay abstract: Elderly patients may have physical difficulties and medical conditions that could challenge or limit the use of immunoglobulin therapy. Recombinant human hyaluronidase-facilitated subcutaneous 10% immunoglobulin (fSCIG) is a treatment that can reduce infections in people who have immunodeficiencies. fSCIG allows for self-administration of a large quantity of IgG, every 3-4 weeks, in the comfort of the patient's home. We report on 16 elderly patients with impaired immune systems who have received at least one treatment of fSCIG. We found that, similar to younger patients, older patients with impaired immune systems could be safely treated with fSCIG at home.Graphical abstract:[GRAPHICS]

O-acetylation of cryptococcal capsular glucuronoxylomannan is essential for interference with neutrophil migration.

Contains fulltext : 58837.pdf (publisher's version ) (Closed access)The capsular polysaccharide glucuronoxylomannan (GXM) of Cryptococcus neoformans has been shown to interfere with neutrophil migration. Although several receptors have been implied to mediate this process, the structural perspectives are unknown. Here, we assess the contribution of 6-O-acetylation and xylose substitution of the (1-->3)-alpha-d-mannan backbone of GXM, the variable structural features of GXM, to the interference with neutrophil migration. We compare chemically deacetylated GXM and acetyl- or xylose-deficient GXM from genetically modified strains with wild-type GXM in their ability to inhibit the different phases of neutrophil migration. Additionally, we verify the effects of de-O-acetylation on neutrophil migration in vivo. De-O-acetylation caused a dramatic reduction of the inhibitory capacity of GXM in the in vitro assays for neutrophil chemokinesis, rolling on E-selectin and firm adhesion to endothelium. Genetic removal of xylose only marginally reduced the ability of GXM to reduce firm adhesion. In vivo, chemical deacetylation of GXM significantly reduced its ability to interfere with neutrophil recruitment in a model of myocardial ischemia (65% reduction vs a nonsignificant reduction in tissue myeloperoxidase, respectively). Our findings indicate that 6-O-acetylated mannose of GXM is a crucial motive for the inhibition of neutrophil recruitment

Antineutrophil cytoplasmic antibodies in sera from colectomised ulcerative colitis patients and its relation to the presence of pouchitis.

BACKGROUND: Few studies have evaluated the influence of colectomy on antineutrophil cytoplasmic antibody (ANCA) positivity in ulcerative colitis (UC). In small series of patients it has been suggested that ANCA positivity in UC might be predictive for development of pouchitis after colectomy. AIMS: To assess the prevalence of ANCA in UC patients treated by colectomy and a Brooke's ileostomy (UC-BI) or ileal pouch anal anastomosis (UC-IPAA), and the relation between the presence of ANCA, the type of surgery, and the presence of pouchitis. SUBJECTS: 63 UC patients treated by colectomy (32 with UC-BI and 31 with UC-IPAA), 54 UC, and 24 controls. METHODS: Samples were obtained at least two years after colectomy. ANCA were detected by indirect immunofluorescent assay. RESULTS: There were no differences between patients with (36.3%) or without pouchitis (35.0%) and between patients with UC (55%), UC-BI (40.6%), and UC-IPAA (35.4%). However, ANCA prevalence significantly decreases in the whole group of operated patients (38.0%) compared with non-operated UC (p = 0.044). CONCLUSIONS: The prevalence of ANCA in operated patients was significantly lower than in non-operated UC, suggesting that it might be related either to the presence of inflamed or diseased tissue. ANCA persistence is not related to the surgical procedure and it should not be used as a marker for predicting the development of pouchitis