To compare the real-world clinical effectiveness and long-term clinical trajectory in patients with Alzheimer disease (AD) treated with combination (COMBO) therapy consisting of ...cholinesterase-inhibitor (CI) plus memantine (MEM) versus CI alone versus no treatment with either.
Three hundred eighty-two subjects with probable AD underwent serial clinical evaluations at a memory disorders unit. Cognition was assessed by the Information-Memory-Concentration subscale of the Blessed Dementia Scale (BDS) and function was assessed by the Weintraub Activities of Daily Living Scale (ADL) at 6-month intervals. One hundred forty-four subjects received standard care without CI or MEM (NO-RX), 122 received CI monotherapy, and 116 received COMBO therapy with CI plus MEM. Mean follow-up was 30 months (4.1 visits) and mean cumulative medication treatment time was 22.5 months. Rates of decline were analyzed using mixed-effects regression models, and Cohen's d effect sizes were calculated annually for years 1 to 4.
Covarying for baseline scores, age, education, and duration of illness, the COMBO group had significantly lower mean annualized rates of deterioration in BDS and ADL scores compared with the CI (P<0.001; Cohen's dBDS=0.10-0.34 and dADL=0.23-0.46 at 1 to 2 y) and NO-RX groups (P<0.001; Cohen's dBDS=0.56-0.73 and dADL=0.32-0.48 at 1 to 2 y). For the COMBO group, Cohen's d effect sizes increased with treatment duration. Similar comparisons significantly favored the CI over the NO-RX group on the BDS.
COMBO therapy slows cognitive and functional decline in AD compared with CI monotherapy and no treatment. These benefits had small-to-medium effect sizes that increased with time on treatment and were sustained for years.
Oduvijek je poznato kako se uređenju terasa i balkona poklanjala velika pažnja, ali prije svega i znanje o pojedinim vrstama cvijeća, kako ih uzgajati, njegovati i održavati. Njega o cvjetnim ...lončanicama ovisi o mjestu na kojem se uzgajaju, supstratu te vremenskim uvjetima koji djeluju na njihov rast i razvoj. Biljke koje se uzgajaju na balkonima i terasama najčešće dolaze iz Sredozemlja, tropskih ili suptropskih područja. Grad Knin ima submediteransku klimu, koju karakteriziraju duge zime s velikom količinom kiše te vruća ljeta s malo oborina. Cilj rada je bio utvrditi percepciju nabave, uporabe, primjene i održavanja cvjetnih vrsta na balkonima i terasama grada Knina metodom anketnog istraživanja. Istraživanje je provedeno tijekom mjeseca lipnja 2016. godine. Na temelju anketnog istraživanja provedenog na građanima Knina i okolice utvrđeni su njihovi stavovi i mišljenja o nabavi, uporabi i primjeni cvjetnih lončanica na terasama i balkonima. Građani su ocjenom vrlo dobar (4,37) među ostalim ocijenili važnost dekoriranja balkona ili terasa cvjetnim lončanicama kako bi se unaprijedila ukupna estetska slika grada. 47,5 % građana grada Knina navodi kako za ukrašavanje svojih balkona i terasa koristi kombinaciju trajnica, jedno i dvogodišnjih cvjetnih vrsta te lukovičastih vrsta. Boravak na balkonu ili terasi ukrašenim cvjetnim lončanicama kao zamjenu za boravak u prirodi ocijenili su ocjenom 4,12. Najmanje preferiraju uporabu cvjetnih lončanica u visećim žardinjerama (3,42).
To evaluate the utility of measuring epigenetic alterations in pancreatic and biliary fluids in determining molecular markers for pancreatobiliary cancers.
DNA was extracted from undiluted pancreatic ...and biliary fluids. As a surrogate for a genome-wide hypomethylation assay, levels of long interspersed nuclear element-1 (LINE-1) methylation were analyzed using bisulfite pyrosequencing. CpG island hypermethylation of 10 tumor-associated genes, aryl-hydrocarbon receptor repressor, adenomatous polyposis coli, calcium channel, voltage dependent, T type α1G subunit, insulin-like growth factor 2, O-6-methyl-guanine-DNA methyltransferase, neurogenin 1, CDKN2A, runt-related transcription factor 3 (RUNX3), secreted frizzled-related protein 1, and ubiquitin carboxyl-terminal esterase L1 (UCHL1), was analyzed using MethyLight. To examine the role of CpG methylation and histone deacetylation in the silencing of UCHL1, human gallbladder carcinoma cell lines and pancreatic carcinoma cell lines were treated with 2 or 5 μmol/L 5-AZA-dC for 72 h or 100 nmol/L Trichostatin A for 24 h. After the treatment, UCHL1 expression was analyzed by real-time reverse transcription-polymerase chain reaction.
Pancreatobiliary cancers exhibited significantly lower LINE-1 methylation levels in pancreatic and biliary fluids than did noncancerous pancreatobiliary disease (58.7% ± 4.3% vs 61.7% ± 2.2%, P = 0.027; 53.8% ± 6.6% vs 57.5% ± 1.7%, P = 0.007); however, LINE-1 hypomethylation was more evident in pancreatic cancer tissues than in pancreatic fluids (45.4% ± 5.5% vs 58.7% ± 4.3%, P < 0.001). CpG island hypermethylation of tumor-associated genes was detected at various frequencies, but it was not correlated with LINE-1 hypomethylation. Hypermethylation of the UCHL1 gene was cancer-specific and most frequently detected in pancreatic (67%) or biliary (70%) fluids from patients with pancreatobiliary cancer. As a single marker, hypermethylation of the UCHL1 gene in pancreatic and biliary fluids was most useful for the detection of pancreatic and pancreatobiliary cancers, respectively (100% specificity). Hypermethylation of the UCHL1 and RUNX3 genes in pancreatic and biliary fluids was the most useful combined marker for pancreatic (87% sensitivity and 100% specificity) and pancreatobiliary (97% sensitivity and 100% specificity) cancers. Treatment with a demethylating agent, 5-AZA-2'-deoxycytidine, restored UCHL1 expression in pancreatobiliary cancer cell lines.
Our results suggest that hypermethylation of UCHL1 and RUNX3 in pancreatobiliary fluid might be useful for the diagnosis of pancreatobiliary cancers.
We present description of a new class for the high-altitude screes of the Caucasus (the Lamio tomentosi-Chaerophylletea humilis) and two alliances such as the Scrophulario minimae-Symphyolomion ...graveolentis (Chaerophylletalia humilis, Lamio tomentosi-Chaerophylletea humilis) and the Scrophulario variegatae-Epilobion dodonaei (Epilobietalia fleischeri, Thlaspietea rotundifolii).
V članku predstavljamo opis novega razreda na visoko ležečih meliščih na Kavkazu (Lamio tomentosi-Lamietea tomentosi) in dveh zvez − Scrophulario minimae-Symphyolomion graveolentis (Chaerophylletalia humilis, Lamio tomentosi- -Chaerophylletea humilis) in Scrophulario variegatae-Epilobion dodonaei (Epilobietalia fleischeri, Thlaspietea rotundifolii).
The terraced landscape in the Brkini hills Ažman Momirski, Lučka; Kladnik, Drago
Acta geographica Slovenica : Geografski zbornik,
01/2015, Letnik:
55, Številka:
1
Journal Article
Recenzirano
Odprti dostop
This article presents cultivated terraces as social and economic landscape elements that are closely connected with natural conditions. The theoretical part, which presents some of the professional ...activities connected with terraced landscapes and examples of studying them around the globe, is followed by a detailed presentation of the features of the unique terraced landscape in the Brkini Hills, Slovenia. Its features, changes, and development trends are placed within the context of the natural features of the area studied, especially its relief conditions and aspect, as well as unfavorable demographic characteristics and modern agricultural trends. Despite modern mechanized farming, the remaining farmers are finding it increasingly more difficult to maintain the cultural landscape. The former tilled terraces were converted into meadows decades ago. Many terraces are being overgrown. Afforestation threatens the future existence of cultural landscapes and affects their development potential and significance as a cultural value.
Terraced landscapes with agricultural terraces are cultural landscapes with a special value. This volume presents them in pictures and words in all their diversity and attractiveness. After ...discussing the global and European dimensions of terraced landscapes and their agricultural terraces, the volume focuses on Slovenian terraced landscapes~they are discussed separately by landscape types, individual regions, and sample cases in the territory of selected settlements (pilot areas). The conclusion also draws attention to the exceptional value and appeal of non-agricultural terraced landscapes that have been shaped by nature and man.
The present study was performed to evaluate the presence and the physiological consequences of butyrylcholinesterase (BChE) inhibition on isolated phrenic‐hemidiaphragm preparations from normal mice ...expressing acetylcholinesterase (AChE) and BChE, and from AChE‐knockout mice (AChE−/−) expressing only BChE.
Histochemical and enzymatic assays revealed abundance of AChE and BChE in normal mature neuromuscular junctions (NMJs).
In normal NMJs, in which release was reduced by low Ca2+/high Mg2+ medium BChE inhibition with tetraisopropylpyrophosphoramide (iso‐OMPA) or bambuterol decreased (∼50%) evoked quantal release, while inhibition of AChE with fasciculin‐1, galanthamine (10, 20 μM) or neostigmine (0.1–1 μM) increased (50–80%) evoked quantal release. Inhibition of both AChE and BChE with galanthamine (80 μM), neostigmine (3–10 μM), O‐ethylS‐2‐(diisopropylamino)ethyl‐methylphosphono‐thioate (MTP) or phospholine decreased evoked transmitter release (20–50%).
In AChE−/− NMJs, iso‐OMPA pre‐treatment decreased evoked release.
Muscarinic toxin‐3 decreased evoked release in both AChE−/− and normal NMJs treated with low concentrations of neostigmine, galanthamine or fasciculin‐1, but had no effect in normal NMJs pretreated with iso‐OMPA, bambuterol, MTP and phospholine.
In normal and AChE−/− NMJs pretreatment with iso‐OMPA failed to affect the time course of miniature endplate potentials and full‐sized endplate potentials.
Overall, our results suggest that inhibition or absence of AChE increases evoked quantal release by involving muscarinic receptors (mAChRs), while BChE inhibition decreases release through direct or indirect mechanisms not involving mAChRs. BChE apparently is not implicated in limiting the duration of acetylcholine action on postsynaptic receptors, but is involved in a presynaptic modulatory step of the release process.
British Journal of Pharmacology (2003) 138, 177–187. doi:10.1038/sj.bjp.0705010
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