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The radiofluorinated levodopa analogue 6-[

F]F-L-DOPA (3,4-dihydroxy-6-

F-L-phenylalanine) is a commonly employed radiotracer for PET/CT imaging of multiple oncological and neurological indications. An unusually large number of different radiosyntheses have been published to the point where two different Ph. Eur. monographs exist depending on whether the chemistry relies on electrophilic or nucleophilic radiosubstitution of appropriate chemical precursors. For new PET imaging sites wishing to adopt [

F]FDOPA into clinical practice, selecting the appropriate production process may be difficult and dependent on the clinical needs of the site.

Data from four years of [

F]FDOPA production at three different clinical sites are collected and compared. These three sites, Aarhus University Hospital (AUH), Odense University Hospital (OUH), and Herlev University Hospital (HUH), produce the radiotracer by different radiosynthetic routes with AUH adopting an electrophilic strategy, while OUH and HUH employ two dilinical applications of the tracer discussed here, including dopamine synthesis in striatum of subjects with schizophrenia and congenital hyperinsulinism in infants.

For most sites either of the two nucleophilic substitution strategies should be favored. However, which of the two will depend on whether a given site wishes to optimize the radiochemical yield or the ease of the use.

For most sites either of the two nucleophilic substitution strategies should be favored. However, which of the two will depend on whether a given site wishes to optimize the radiochemical yield or the ease of the use.Desiccation tolerance was a key trait that allowed plants to colonize land. However, little is known about the transition from desiccation tolerant non-vascular plants to desiccation sensitive vascular ones. Ozanimod chemical structure Filmy ferns (Hymenophyllaceae) represent a useful system to investigate how water-stress strategies differ between non-vascular and vascular stages within a single organism because they have vascularized sporophytes and nonvascular gametophytes that are each capable of varying degrees of desiccation tolerance. To explore this, we surveyed sporophytes and gametophytes of 19 species (22 taxa including varieties) of filmy ferns on Moorea (French Polynesia) and used chlorophyll fluorescence to measure desiccation tolerance and light responses. We conducted phylogenetically informed analyses to identify differences in physiology between life stages and growth habits. Gametophytes had similar or less desiccation tolerance (ability to recover from 2 days desiccation at - 86 MPa) and lower photosynthetic optima (maximum electron transport rate of photosystem II and light level at 95% of that rate) than sporophytes. Epiphytes were more tolerant of desiccation than terrestrial species in both life stages. Despite their lack of greater physiological tolerances, gametophytes of several species occurred over a wider elevational range than conspecific sporophytes. Our results demonstrate that filmy fern gametophytes and sporophytes differ in their physiology and niche requirements, and point to the importance of microhabitat in shaping the evolution of water-use strategies in vascular plants.

Alpelisib is newly-available breast cancer agent that targets PIK3 mutations and confers a somewhat unusual adverse event profile. This study focused on older patients (≥ 65years of age) treated outside a clinical trial to gain further experience on how these under-studied patients do with this new agent.

This descriptive, multi-site study relied on medical record review.

Fifty-one older breast cancer patients were started on alpelisib between May 2019 and September 2020. The median age and number of comorbidities at alpelisib initiation was 71years and 4, respectively. Thirty-five patients had stopped alpelisib (median time on drug 2.6months (range < 1, 9.5months)) for the following reasons alpelisib adverse events (n = 15), cancer progression (n = 13), and other/unknown (n = 7). Alpelisib adverse events included hyperglycemia (n = 37), diarrhea (n = 23), rash (n = 19), fatigue (n = 12), and mouth sores (n = 7); (numbers in parentheses indicate the number of patients with at least one such event). Five patients were hospitalized for hyperglycemia. At the time of report, 14 patients were deceased, and median survival had not been reached.

Older patients might derive further benefit from alpelisib if the adverse event profile of this agent, particularly the hyperglycemia, were able to be better managed.

Older patients might derive further benefit from alpelisib if the adverse event profile of this agent, particularly the hyperglycemia, were able to be better managed.

Impaired DNA repair mechanism is one of the cancer hallmarks. Flap Endonuclease 1 (FEN1) is essential for genomic integrity. FEN1 has key roles during base excision repair (BER) and replication. We hypothesised a role for FEN1 in breast cancer pathogenesis. This study aims to assess the role of FEN1 in breast ductal carcinoma in situ (DCIS).

Expression of FEN1 protein was evaluated in a large (n = 1015) well-characterised cohort of DCIS, comprising pure (n = 776) and mixed (DCIS coexists with invasive breast cancer (IBC); n = 239) using immunohistochemistry (IHC).

FEN1 high expression in DCIS was associated with aggressive and high-risk features including higher nuclear grade, larger tumour size, comedo type necrosis, hormonal receptors negativity, higher proliferation index and triple-negative phenotype. DCIS coexisting with invasive BC showed higher FEN1 nuclear expression compared to normal breast tissue and pure DCIS but revealed significantly lower expression when compared to the invasive component. However, FEN1 protein expression in DCIS was not an independent predictor of local recurrence-free interval.

High FEN1 expression is linked to features of aggressive tumour behaviour and may play a role in the direct progression of DCIS to invasive disease. Further studies are warranted to evaluate its mechanistic roles in DCIS progression and prognosis.

High FEN1 expression is linked to features of aggressive tumour behaviour and may play a role in the direct progression of DCIS to invasive disease. Further studies are warranted to evaluate its mechanistic roles in DCIS progression and prognosis.

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