Painful skin lesions and squamous cell carcinoma predict overall mortality risk in organ transplant recipients:a cohort study

Item does not contain fulltextBACKGROUND: Organ transplant recipients (OTRs) have a highly increased risk of cutaneous squamous cell carcinomas (SCCs). Sensation of pain in cutaneous tumours is a powerful patient-reported warning signal for invasive SCCs in OTRs. OBJECTIVES: To investigate the impact of painful vs. painless skin lesions and SCC vs. other skin lesions on the overall mortality risk in OTRs. METHODS: We followed 410 OTRs from 10 different centres across Europe and North America between 2008 and 2015. These patients had been enrolled in an earlier study to define clinically meaningful patient-reported warning signals predicting the presence of SCC, and had been included if they had a lesion requiring histological diagnosis. Cumulative incidences of overall mortality were calculated using Kaplan-Meier survival analysis, and risk factors were analysed with Cox proportional hazard analysis. RESULTS: There was an increased overall mortality risk in OTRs who reported painful vs. painless skin lesions, with a hazard ratio (HR) of 1.6 [95% confidence interval (CI) 0.97-2.7], adjusted for age, sex and other relevant factors. There was also an increased overall mortality risk in OTRs diagnosed with SCC compared with other skin lesions, with an adjusted HR of 1.7 (95% CI 1.0-2.8). Mortality due to internal malignancies and systemic infections appeared to prevail in OTRs with SCC. CONCLUSIONS: We suggest that OTRs have an increased overall mortality risk if they develop painful skin lesions or are diagnosed with cutaneous SCC

Activation of BKCa Channels in Zoledronic Acid-Induced Apoptosis of MDA-MB-231 Breast Cancer Cells

BACKGROUND: Zoledronic acid, one of the most potent nitrogen-containing biphosphonates, has been demonstrated to have direct anti-tumor and anti-metastatic properties in breast cancer in vitro and in vivo. In particular, tumor-cell apoptosis has been recognized to play an important role in the treatment of metastatic breast cancer with zoledronic acid. However, the precise mechanisms remain less clear. In the present study, we investigated the specific role of large conductance Ca(2+)-activated potassium (BK(Ca)) channel in zoledronic acid-induced apoptosis of estrogen receptor (ER)-negative MDA-MB-231 breast cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: The action of zoledronic acid on BK(Ca) channel was investigated by whole-cell and cell-attached patch clamp techniques. Cell apoptosis was assessed with immunocytochemistry, analysis of fragmented DNA by agarose gel electrophoresis, and flow cytometry assays. Cell proliferation was investigated by MTT test and immunocytochemistry. In addition, such findings were further confirmed with human embryonic kidney 293 (HEK293) cells which were transfected with functional BK(Ca) α-subunit (hSloα). Our results clearly indicated that zoledronic acid directly increased the activities of BK(Ca) channels, and then activation of BK(Ca) channel by zoledronic acid contributed to induce apoptosis in MDA-MB-231 cells. The possible mechanisms were associated with the elevated level of intracellular Ca(2+) and a concomitant depolarization of mitochondrial membrane potential (Δψm) in MDA-MB-231 cells. CONCLUSIONS: Activation of BK(Ca) channel was here shown to be a novel molecular pathway involved in zoledronic acid-induced apoptosis of MDA-MB-231 cells in vitro

Recovery of dialysis patients with COVID-19 : health outcomes 3 months after diagnosis in ERACODA

Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis

Wplyw nawozenia weglem brunatnym na wlasciwosci materii organicznej gleb

W doświadczeniach polowych przeprowadzonych na glebie płowej i brunatnej badano wpływ nawożenia preparatem otrzymanym z węgla brunatnego na właściwości substancji humusowych. Badano skład frakcyjny materii organicznej i skład pierwiastkowy kwasów huminowych. W wyseparowanych kwasach huminowych oznaczono właściwości spektrometryczne (UV-VIS, IR) oraz parametry termicznego rozkładu w derywatografie. Stwierdzono, że nawożenie gleb węglem brunatnym zwiększa ich właściwości sorpcyjne oraz zawartość węgla organicznego. W składzie frakcyjnym dominują frakcje kwasów huminowych oraz humin. Kwasy huminowe gleb nawożonych węglem brunatnym charakteryzują się wysokimi wartościami absorbancji, wyższymi niż gleb nienawożonych, oraz niższą masą cząsteczkową niż kwasy huminowe gleb płowej i brunatnej. Kwasy huminowe gleb nawożonych węglem brunatnym, w porównaniu z kwasami huminowymi gleb nienawożonych, charakteryzują się większą aromatycznością, większą zawartością grup karboksylowych i hydroksylowych, są bardziej odporne na rozkład termiczny.Effects of fertilization with a preparation obtained from brown coal on humus substance properties were studied in fields experiments. Fractional composition of organic matter and elemental composition of humic acids were studied. The isolated humic acids were analysed for their spectral properties (UV-VIS, IR) and the parameters of thermal decomposition in a derivatograph. It was found that the soil fertilization with brown coal improved soil sorption properties and increased organic carbon content. Humic acids fraction and humines prevailed in fractional composition. Humic acids of the soils fertilized with brown coal showed absorbtion values higher than the non-fertilized soils, while their molecular weight was lower than that of humic acids of podzolic and the brown soils. Humic acids of the soils fertilized with brown coal revealed higher content of carboxyl and hydroxyl functional groups and were more resistant to thermal decomposition than those of non-fertilized soils

Content and changes in dissolved organic matter in meadow and arable soils over time

Considering the discrepancies in the reports on seasonal changes in the content of dissolved organic carbon, this paper concerns the research which aimed at defining the content and seasonal changes in dissolved organic matter (DOM) in arable and meadow soils in moderate climate conditions. The research has involved the soils sampled in the kujawsko-pomorskie province (Poland). Gleic Phaeozems (meadow soils), Brunic Arenosols and Eutric Cambisols were sampled from the depth of 0-30 cm, 30-60 cm and 60-100 cm, November 2011 through September 2013. The soil samples were analyzed for dry weight content, pH, content of total organic carbon and total nitrogen. DOM was extracted with 0.004 mol·dm⁻³ CaCl₂, in the extracts the content of dissolved organic carbon (DOC) and dissolved nitrogen (DNt) were assayed. The share of DOC was determined by the soil management. The analysis of variance did not show significant differences in the content of TOC and Nt across the soil sampling dates. Were recorded changes in DOC and DNt between successive sampling dates; for topsoil for DOC – from -12.06% to 13.34% (meadow soils) and for DNt -40.84% to 47.44% (arable soils)

Dependence of energy gap on x and T in Zn1-xMnxSe: The role of exchange interaction

Photoluminescence and reflectivity measurements have been carried out on Zn1-xMnxSe solid solutions in the complete range of crystal compositions, 0x0.55. The features of the photoluminescence and reflectivity data near the band edge enabled us to determine values of the fundamental band gap as a function of Mn molar fraction x and temperature (8 KT 300 K). The energy gap in crystals with compositions in the vicinity of the zinc-blende wurtzite structural transition (0.2x0.3) exhibited a scatter of values, probably associated with the presence of various polytypes (as evidenced by transmission-electron-microscopy measurements). The dependence of Eg on x is anomalous for 0x0.2, showing a minimum in the Eg vs x curve. A simple model (in terms of second-order perturbation theory in s-d and p-d interactions) relates this minimum to a maximum observed in the magnetic susceptibility as a function of x. For samples with x0.35, the Eg dependence on T shows an onset of an additional blue shift as the temperature is lowered below 150 K. This onset, though not reproduced by our simple calculation, appears to be also related to the presence of s-d and p-d interactions. © 1986 The American Physical Society

Immunosenescence increases the rate of acceptance of kidney allotransplants in elderly recipients through exhaustion of CD4+ T-cells.

Compromised immunity is the hallmark of ageing. Paradoxically, it may be "an ally" in facilitating acceptance of allogeneic grafts in the elderly. In this retrospective study we looked for biomarkers of immunosenescence that distinguish elderly recipients less prone to reject kidney allografts. Recruited kidney recipients aged > or = 60 or < 60 were designated 'elderly' and 'young', respectively. Both age-groups were divided according to the history of acute rejection. The phenotype, length of telomeres, expression of FoxP3 and proliferative responses were assessed in CD4(+) and CD8(+) T-cell subsets. In addition, IL6, IL10 and TGFbeta were measured on the level of mRNA and serum protein. Acute-rejection-free history in elderly transplant recipients was associated with short telomeres, a decreased proportion of CD28(+) T-cells associated with CMV-seropositivity and low proliferation of CD4(+) T-cells. In contrast, elderly recipients who experienced acute rejection kept preserved telomere length, had a higher number of functional CD4(+)CD28(+) cells and exhibited vigorous proliferation in vitro. These differences were not found in the young group. The major conclusion of this study is that the impaired condition of CD4(+) T-cells, so-called immunosenescence, renders transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients of > 60 years of age