Genetic Variation of the Serotonin 2a Receptor Affects Hippocampal Novelty Processing in Humans

Serotonin (5-hydroxytryptamine, 5-HT) is an important neuromodulator in learning and memory processes. A functional genetic polymorphism of the 5-HT 2a receptor (5-HTR2a His452Tyr), which leads to blunted intracellular signaling, has previously been associated with explicit memory performance in several independent cohorts, but the underlying neural mechanisms are thus far unclear. The human hippocampus plays a critical role in memory, particularly in the detection and encoding of novel information. Here we investigated the relationship of 5-HTR2a His452Tyr and hippocampal novelty processing in 41 young, healthy subjects using functional magnetic resonance imaging (fMRI). Participants performed a novelty/familiarity task with complex scene stimuli, which was followed by a delayed recognition memory test 24 hours later. Compared to His homozygotes, Tyr carriers exhibited a diminished hippocampal response to novel stimuli and a higher tendency to judge novel stimuli as familiar during delayed recognition. Across the cohort, the false alarm rate during delayed recognition correlated negatively with the hippocampal novelty response. Our results suggest that previously reported effects of 5-HTR2a on explicit memory performance may, at least in part, be mediated by alterations of hippocampal novelty processing

The ERA Registry Annual Report 2021:a summary

BackgroundThe European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD). This paper is a summary of the ERA Registry Annual Report 2021, including a comparison across treatment modalities.MethodsData was collected from 54 national and regional registries from 36 countries, of which 35 registries from 18 countries contributed individual patient data and 19 registries from 19 countries contributed aggregated data. Using this data, incidence and prevalence of KRT, kidney transplantation rates, survival probabilities and expected remaining lifetimes were calculated.ResultsIn 2021, 533.2 million people in the general population were covered by the ERA Registry. The incidence of KRT was 145 per million population (pmp). In incident patients, 55% were 65 years or older, 64% were male, and the most common primary renal disease (PRD) was diabetes (22%). The prevalence of KRT was 1040 pmp. In prevalent patients, 47% were 65 years or older, 62% were male, and the most common PRDs were diabetes and glomerulonephritis/sclerosis (both 16%). On 31 December 2021, 56% of patients received haemodialysis, 5% received peritoneal dialysis, and 39% were living with a functioning graft. The kidney transplantation rate in 2021 was 37 pmp, a majority coming from deceased donors (66%). For patients initiating KRT between 2012–2016, 5-year survival probability was 52%. Compared to the general population, life expectancy was 65% and 68% shorter for males and females receiving dialysis, and 40% and 43% shorter for males and females living with a functioning graft

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

The ERA Registry Annual Report 2019 : summary and age comparisons

Background Data on renal replacement therapy (RRT) for end-stage renal disease were collected by the European Renal Association (ERA) Registry via national and regional renal registries in Europe and countries bordering the Mediterranean Sea. This article provides a summary of the 2019 ERA Registry Annual Report, including data from 34 countries and additional age comparisons. Methods Individual patient data for 2019 were provided by 35 registries and aggregated data by 17 registries. Using these data, the incidence and prevalence of RRT, the kidney transplantation activity and the survival probabilities were calculated. Results In 2019, a general population of 680.8 million people was covered by the ERA Registry. Overall, the incidence of RRT was 132 per million population (p.m.p.). Of these patients, 62% were men, 54% were >= 65 years of age and 21% had diabetes mellitus as primary renal disease (PRD), and 84% had haemodialysis (HD), 11% had peritoneal dialysis (PD) and 5% had pre-emptive kidney transplantation as an initial treatment modality. The overall prevalence of RRT on 31 December 2019 was 893 p.m.p., with 58% of patients on HD, 5% on PD and 37% living with a kidney transplant. The overall kidney transplant rate was 35 p.m.p. and 29% of the kidney grafts were from a living donor. The unadjusted 5-year survival probability was 42.3% for patients commencing dialysis, 86.6% for recipients of deceased donor grafts and 94.4% for recipients of living donor grafts in the period 2010-14. When comparing age categories, there were substantial differences in the distribution of PRD, treatment modality and kidney donor type, and in the survival probabilities.Peer reviewe

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

Charakterystyka kwasow huminowych powstalych w procesie rozkladu resztek roslinnych

Zbadano wpływ czasu inkubacji resztek roślinnych kukurydzy, lucerny i pszenicy na właściwości optyczne i strukturę kwasów huminowych. Badania prowadzono w oparciu o modelowe doświadczenie laboratoryjne. Dla wyseparowanych kwasów huminowych wykonano analizy właściwości optycznych, widm w podczerwieni i ultrafiolecie. Wykazano, że nawożenie resztkami pozbiorowymi modyfikuje właściwości kwasów huminowych. Podczas rozkładu resztek pozbiorowych lucerny i kukurydzy w porównaniu z resztkami pozbiorowymi pszenicy, powstają kwasy huminowe w mniejszym stopniu różniące się właściwościami od kwasów huminowych gleby. Stwierdzono ponadto, że właściwości kwasów huminowych wyekstrahowanych z resztek pszenicy, odbiegają od właściwości tych kwasów wyodrębnionych z lucerny i kukurydzy.Influence of incubation time on decomposition of plant residues (maize, alfalfa and wheat) on the optical properties and structure of humic acids was examined. For isolated humic acids, the analysis of optical properties as well as IR- and UV-spectra were made. During decomposition of alfalfa and maize residues there are produced humic acids which differ less so that from soil. The decomposition products of wheat residues caused specific changes in optical properties and structure of humic acids, with comparision to humic acids from soil and other plant residues

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