Oncologists' reflections on patient rights and access to compassionate use drugs: A qualitative interview study from an academic cancer center.

The U.S. Food and Drug Administration (FDA) allows patients with serious illnesses to access investigational drugs for "compassionate use" outside of clinical trials through expanded access (EA) Programs.

"I Think It's Been Met With a Shrug:" Oncologists' Views Toward and Experiences With Right-to-Try.

Background: The federal Right-to-Try (RTT) Act created an alternate regulatory pathway for preapproval access to investigational drugs. A few studies have examined the experiences of physicians with the Food and Drug Administration's Expanded Access Programs, but to our knowledge, no study has yet to examine their attitudes and experiences toward RTT.

Methods: This study explored the views of 21 oncologists at a major cancer center with 3 main sites across the United States using semi-structured interviews and qualitative analysis.

Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease.

Background: Senescent cells, which can release factors that cause inflammation and dysfunction, the senescence-associated secretory phenotype (SASP), accumulate with ageing and at etiological sites in multiple chronic diseases. Senolytics, including the combination of Dasatinib and Quercetin (D + Q), selectively eliminate senescent cells by transiently disabling pro-survival networks that defend them against their own apoptotic environment. In the first clinical trial of senolytics, D + Q improved physical function in patients with idiopathic pulmonary fibrosis (IPF), a fatal senescence-associated disease, but to date, no peer-reviewed study has directly demonstrated that senolytics decrease senescent cells in humans.

Fisetin is a senotherapeutic that extends health and lifespan.

Background: Senescence is a tumor suppressor mechanism activated in stressed cells to prevent replication of damaged DNA. Senescent cells have been demonstrated to play a causal role in driving aging and age-related diseases using genetic and pharmacologic approaches. We previously demonstrated that the combination of dasatinib and the flavonoid quercetin is a potent senolytic improving numerous age-related conditions including frailty, osteoporosis and cardiovascular disease.

New agents that target senescent cells: the flavone, fisetin, and the BCL-X inhibitors, A1331852 and A1155463.

Senescent cells accumulate with aging and at sites of pathology in multiple chronic diseases. Senolytics are drugs that selectively promote apoptosis of senescent cells by temporarily disabling the pro-survival pathways that enable senescent cells to resist the pro-apoptotic, pro-inflammatory factors that they themselves secrete. Reducing senescent cell burden by genetic approaches or by administering senolytics delays or alleviates multiple age- and disease-related adverse phenotypes in preclinical models.

High cumulative live births in oocyte donation cycles with cryopreservation of all embryos.

Background: Cryopreservation of all embryos in stimulated IVF cycles is occasionally necessary. Although it is known that frozen embryo transfer results in lower live birth rates per transfer, there is limited information regarding expected cumulative live birth rates for patients who are in this particular scenario.

Methods: The objective was to evaluate long-term outcomes in cycles undergoing pronuclear cryopreservation of all embryos utilizing a retrospective analysis of 154 consecutive recipients from 1995 to 2006.

Ovarian hyperstimulation syndrome: steps to maximize success and minimize effect for assisted reproductive outcome.

Objective: To investigate the strategies used to decrease the risk of ovarian hyperstimulation syndrome (OHSS) and their impact on pregnancy and live birth rates.

Design: Retrospective cohort analysis.

Setting: University hospital.

Frozen-thawed embryo transfer and live birth: Long-term follow-up after one oocyte retrieval.

Frozen-thawed embryos accounted for 39% (249 of 639) of live births from 931 consecutive first oocyte retrievals after median follow-up of 6.5 years with consistent use of pronuclear-stage freezing and cleavage-stage transfer. Survival after thaw was 95% (2,129 of 2,247).

Plasticity in the composition of the light harvesting antenna of higher plants preserves structural integrity and biological function.

Arabidopsis plants in which the major trimeric light harvesting complex (LHCIIb) is eliminated by antisense expression still exhibit the typical macrostructure of photosystem II in the granal membranes. Here the detailed analysis of the composition and the functional state of the light harvesting antennae of both photosystem I and II of these plants is presented. Two new populations of trimers were found, both functional in energy transfer to the PSII reaction center, a homotrimer of CP26 and a heterotrimer of CP26 and Lhcb3.

Differential adaptation of two varieties of common bean to abiotic stress: II. Acclimation of photosynthesis.

The photosynthetic characteristics of two contrasting varieties of common bean (Phaseolus vulgaris) have been determined. These varieties, Arroz and Orfeo, differ in their productivity under stress conditions, resistance to drought stress, and have distinctly different stomatal behaviour. When grown under conditions of high irradiance and high temperature, both varieties displayed evidence of photosynthetic acclimation at the chloroplast level-there was an increase in chlorophyll a/b ratio, a decreased content of Lhcb proteins, and an increased xanthophyll cycle pool size.

Differential adaptation of two varieties of common bean to abiotic stress: I. Effects of drought on yield and photosynthesis.

The yield of 24 commercial varieties and accessions of common bean (Phaseolus vulgaris) has been determined at different sites in Chile and Bolivia. Statistical analysis was performed in order to characterize whether a particular variety was more or less stable in yield under different environmental conditions. Amongst these, two varieties have been identified for more detailed study: one variety has a higher than average yield under unstressed conditions but is strongly affected by stress, and another has a reduced yield under unstressed conditions but is less affected by stress.

Control of the light harvesting function of chloroplast membranes: the LHCII-aggregation model for non-photochemical quenching.

Dissipation of excess excitation energy within the photosystem II light-harvesting antenna (LHCII) by non-photochemical quenching (NPQ) is an important photoprotective process in plants. An update to a hypothesis for the mechanism of NPQ [FEBS Letters 292, 1991] is presented. The impact of recent advances in understanding the structure, organisation and photophysics of LHCII is assessed.

The functional significance of the monomeric and trimeric states of the photosystem II light harvesting complexes.

The main light harvesting complex of photosystem II in plants, LHCII, exists in a trimeric state. To understand the biological significance of trimerization, a comparison has been made been LHCII trimers and LHCII monomers prepared by treatment with phospholipase. The treatment used caused no loss of chlorophyll, but there was a difference in carotenoid composition, together with the previously observed alterations in absorption spectrum.

The effects of manipulating phospholipase C on guard cell ABA-signalling.

Studies using stably transformed tobacco plants containing very low levels of PI-PLC in their guard cells show that this enzyme plays a role in the events associated with the inhibition of stomatal opening by ABA, but not in the cellular reactions that are responsible for ABA-induced stomatal closure. However, Commelina communis guard cells microinjected with the InsP3 antagonist, heparin, fail to close on addition of ABA. There are three possible explanations for this apparent data mismatch.

Absence of the Lhcb1 and Lhcb2 proteins of the light-harvesting complex of photosystem II - effects on photosynthesis, grana stacking and fitness.

We have constructed Arabidopsis thaliana plants that are virtually devoid of the major light-harvesting complex, LHC II. This was accomplished by introducing the Lhcb2.1 coding region in the antisense orientation into the genome by Agrobacterium-mediated transformation.

Thermodynamic investigation into the mechanism of the chlorophyll fluorescence quenching in isolated photosystem II light-harvesting complexes.

Chlorophyll fluorescence quenching can be stimulated in vitro in purified photosystem II antenna complexes. It has been shown to resemble nonphotochemical quenching observed in isolated chloroplasts and leaves in several important respects, providing a model system for study of the mechanism of photoprotective energy dissipation. The effect of temperature on the rate of quenching in trimeric and monomeric antenna complexes revealed the presence of two temperature-dependent processes with different activation energies, one between approximately 15 and 35 degrees C and another between approximately 40 and 60 degrees C.

In vitro reconstitution of the activated zeaxanthin state associated with energy dissipation in plants.

Dissipation of excess light energy in plant photosynthetic membranes plays an important role in the response of plants to the environment, providing short-term balancing between the intensity of sunlight and photosynthetic capacity. The carotenoid zeaxanthin and the photosystem II subunit PsbS play vital roles in this process, but the mechanism of their action is largely unexplained. Here we report that the isolated photosystem II subunit PsbS was able to bind exogenous zeaxanthin, the binding resulting in a strong red shift in the absorption spectrum, and the appearance of characteristic features in the resonance Raman spectrum and a distinct circular dichroism spectrum, indicating pigment-protein, as well as specific pigment-pigment, interaction.