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ObjectiveTo determine whether metformin or lifestyle modification can lower rates of all-cause and cause-specific mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study.Research design and methodsFrom 1996 to 1999, 3,234 adults at high risk for type 2 diabetes were randomized to an intensive lifestyle intervention, masked metformin, or placebo. Placebo and lifestyle interventions stopped in 2001, and a modified lifestyle program was offered to everyone, but unmasked study metformin continued in those originally randomized. Causes of deaths through 31 December 2018 were adjudicated by blinded reviews. All-cause and cause-specific mortality hazard ratios (HRs) were estimated from Cox proportional hazards regression models and Fine-Gray models, respectively.ResultsOver a median of 21 years (interquartile range 20-21), 453 participants died. Cancer was the leading cause of death (n = 170), followed by cardiovascular disease (n = 131). Compared with placebo, metformin did not influence mortality from all causes (HR 0.99 [95% CI 0.79, 1.25]), cancer (HR 1.04 [95% CI 0.72, 1.52]), or cardiovascular disease (HR 1.08 [95% CI 0.70, 1.66]). Similarly, lifestyle modification did not impact all-cause (HR 1.02 [95% CI 0.81, 1.28]), cancer (HR 1.07 [95% CI 0.74, 1.55]), or cardiovascular disease (HR 1.18 [95% CI 0.77, 1.81]) mortality. Analyses adjusted for diabetes status and duration, BMI, cumulative glycemic exposure, and cardiovascular risks yielded results similar to those for all-cause mortality.ConclusionsCancer was the leading cause of mortality among adults at high risk for type 2 diabetes. Although metformin and lifestyle modification prevented diabetes, neither strategy reduced all-cause, cancer, or cardiovascular mortality rates.

Ex-combatants, war victims, and violence-affected community members are typically forced to live together as neighbors in post-conflict settings. Cases all over the world accumulate evidence on the fact that living together after war is a far from a harmonic endeavor, and individuals usually rely on contention mechanisms to keep on with their daily lives while in proximity of former and present-day antagonists. While decades-long academic research has unveiled a series of favorable conditions under which interactions might generate positive effects on intergroup dispositions, they usually prescribe focusing less on touching upon divisive issues, and more on emphasizing in potentially bonding commonalities. By means of a randomized controlled experiment with former war antagonists in Colombia, we set to explore whether avoidance or addressing of the most sensitive issues affecting intergroup relations yield better results in terms of attitude change under favorable conditions. Experimental effects show that perspective-giving protocols are capable of containing polarization tendencies in intergroup discussions even when participants are incentivized to directly address their co-existence problems, while qualitative analysis points out at silences and other avoidance mechanisms as the participants' key strategies to contain conflict when contentious topics flare up during discussions. [ABSTRACT FROM AUTHOR]

Tailoring the electromechanical properties of a material without altering the original composition is an emerging phenomenon for the optimization of functional properties. Post-sintering annealing with varying maximum temperatures, cooling rates, and atmospheres can influence the crystallographic phases, domain structures, conductivity, mechanical properties, and the temperature stability of the electromechanical properties. K1/2Bi1/2TiO3 (KBT) is a high-temperature stable >280 °C A-site complex perovskite piezoelectric and is critical for high-temperature applications. However, the influence of annealing conditions on crystal structure, domain structure, and functional properties is not well-known. This work demonstrates the effect of annealing cooling rate and maximum temperature on the macroscopic electromechanical response as well as the crystal and domain structure. It is shown that the room-temperature state of KBT can be reversibly switched between the ferroelectric and relaxor state, where the slow cooling from 900 °C favors the stabilization of the relaxor state and quenching induces the ferroelectric state. Importantly, the quenched sample showed a stable piezoelectric coefficient up to 368 °C in the depolarization temperature, an increase of 78 °C. The origin of ferroelectric-relaxor state change is proposed to be related to the A-site cation redistribution and the associated change in the crystal structure and domain structure. [ABSTRACT FROM AUTHOR]

The theory that science, technology and innovation (STI) policies in Canada are regionalized due to its networked system is studied. The design of federal countries was observed to entail difficulties in formulating STI policies. The forming of networks as a result of STI policies in Canada, and as an important aspect of regional development and of industrial cluster promotion, is examined.

Na1/2Bi1/2TiO3‐based materials have been earmarked for one of the first large‐volume applications of lead‐free piezoceramics in high‐power ultrasonics. Zn2+‐doping is demonstrated as a viable route to enhance the thermal depolarization temperature and electromechanically harden (1‐y)Na1/2Bi1/2TiO3‐yBaTiO3 (NBT100yBT) with a maximum achievable operating temperature of 150 °C and mechanical quality factor of 627 for 1 mole % Zn2+‐doped NBT6BT. Although quenching from sintering temperatures has been recently touted to enhance TF‐R, with quenching the doped compositions featuring an additional increase in TF‐R by 17 °C, it exhibits negligible effect on the electromechanical properties. The effect is rationalized considering the missing influence on conductivity and therefore, negligible changes in the defect chemistry upon quenching. High‐resolution diffraction indicates that Zn2+‐doped samples favor the tetragonal phase with enhanced lattice distortion, further corroborated by 23Na Nuclear Magnetic Resonance investigations. [ABSTRACT FROM AUTHOR]

Progesterone (P4), a steroid produced during estrous cycles and gestation for maintenance of pregnancy, also plays key roles in breast development to allow lactation post-parturition. Progestins (P4 and related steroids) are also implicated in breast cancer etiology. Hormone replacement therapy containing both estrogen and progestins increases breast cancer incidence while estrogen hormone therapy lowers breast cancer risk. P4 signaling via nuclear P4 receptors (PRs) has been extensively studied in breast cancer, however, progestin signaling via non-classical membrane bound progestin receptors (MPRs and PGRMC1) remains unclear. Moreover, P4 metabolites and synthetic progestins may bind membrane progestin receptors. We hypothesized that PR-negative breast epithelial cells express non-classical progestin receptors, which activate intracellular signaling pathways differently depending on nature of progestin. Therefore, our objectives for the current study were to determine expression of MPRs and PGRMC1 in two PR-negative non-tumorigenic breast epithelial cell lines, assess progestin-mediated signaling and biological functions. We determined five MPR isoforms and PGRMC1 were present in MCF10A cells and all progestin receptors but MPRβ in MCF12A cells. MCF10A and MCF12A cells were treated with P4, select P4 metabolites (5αP and 3αHP), medroxyprogesterone acetate (MPA), or a specific MPR-Agonist (MPR-Ag) and phosphorylation of ERK, p38, JNK, and AKT was characterized following treatment. To our knowledge this is the first report of ERK and JNK activation in MCF10A and MCF12A cells with P4, P4 metabolites, MPA, and MPR-Ag. Activation of ERK and JNK in cells treated with MPR-Ag implicates MPRs may serve as the receptors responsible for their activation. In contrast, p38 activation varied with cell type and with progestin treatment. P4 and MPA promoted AKT phosphorylation in the MCF12A cell line only whereas no activation was observed in MCF10A cells. Interestingly, cellular proliferation increased in MCF10A cells treated with MPA or 5αP, while MPR-Ag tended to slightly decrease proliferation. Collectively, our data highlights the importance of investigating the effects of synthetic progestins in breast cancer biology. Our results add to the understanding that various progestins have on breast epithelial cells and underscores the importance of considering both membrane bound receptors and progestin type in breast cancer development. [ABSTRACT FROM AUTHOR]

The basis of this paper is to go beyond abstract definitions of what a cluster is, and look at a variety of measurable indicators, to see which can demonstrate the presence of a cluster. The example presented is based on the biotechnology industry in Vancouver, Canada. Biotechnology differs from conventional industries, in that there are few tangible goods or services traded, but rather the basis of value creation is primarily the sale or licensing of intangible intellectual property or the (usually pre-revenue) firms themselves. The two main questions we aim to test are (i) is there a biotechnology cluster in Vancouver, and (ii) what are its inputs, outcomes, and impact on the region? We use data provided from local and federal agencies such as LifeSciences British Columbia and Statistics Canada to compare biotechnology R&D activity across regions, and within the local economy. Our findings indicate that there is significant activity around biotechnology R&D and commercialisation in Vancouver, but no guarantee of the longevity of the innovation system.Journal of Commercial Biotechnology (2008) 14, 233–246. doi:10.1057/jcb.2008.16; published online 3 June 2008 [ABSTRACT FROM AUTHOR]

Na1/2Bi1/2TiO3‐based materials have been earmarked for one of the first large‐volume applications of lead‐free piezoceramics in high‐power ultrasonics. Zn2+‐doping is demonstrated as a viable route to enhance the thermal depolarization temperature and electromechanically harden (1‐y)Na1/2Bi1/2TiO3‐yBaTiO3 (NBT100yBT) with a maximum achievable operating temperature of 150 °C and mechanical quality factor of 627 for 1 mole % Zn2+‐doped NBT6BT. Although quenching from sintering temperatures has been recently touted to enhance TF‐R, with quenching the doped compositions featuring an additional increase in TF‐R by 17 °C, it exhibits negligible effect on the electromechanical properties. The effect is rationalized considering the missing influence on conductivity and therefore, negligible changes in the defect chemistry upon quenching. High‐resolution diffraction indicates that Zn2+‐doped samples favor the tetragonal phase with enhanced lattice distortion, further corroborated by 23Na Nuclear Magnetic Resonance investigations. [ABSTRACT FROM AUTHOR]

Date Presented 4/1/2017 This study examined ideational skills and playfulness in children with and without autism spectrum disorder (ASD). Children with ASD had poorer ideational skills than typical peers. No relation was found between ideation and playfulness. Results inform an understanding of ideational skills in children with autism. Primary Author and Speaker: Teresa A. May-Benson Additional Authors and Speakers: Caitlin B. Lauchlan, Monica Nicole Salazar, Hannah Polshuk, Christina Rogers, Sarah Sherman Contributing Authors: Alison Teasdale [ABSTRACT FROM AUTHOR]

Objective: It has been demonstrated in vitro that acetylsalicylic acid (ASA) treatment halves hepatitis C virus (HCV) expression in hepatocarcinoma cells. However, the signaling pathway that promotes this ASA-induced antiviral effect has not yet been identified., Aim: The aim of this work was to identify alterations in the transcriptional profile of Huh-7-HCV-subgenomic replicon cells with vs. without ASA treatment. This comparison sheds light onto the signaling pathways and molecular mechanisms involved in the antiviral effects of ASA., Methods: Human hepatocellular carcinoma (Huh-7) cells that express non-structural HCV proteins (Huh-7-HCV-replicon cells) were exposed to 4 mM ASA for 0, 24, 48, and 72 hours. Total RNA was isolated, and cDNA was synthesized. Transcripts were then tagged with biotin and purified. Thereafter, they were fragmented and hybridized on HG-U133 Plus 2 Gene Expression chips. Hybridization signals were captured using a GeneChip 3000 7G Scanner and analyzed via Expression Console and dChip Software., Results: When exposed to ASA, hepatocarcinoma cells with non-structural HCV proteins were found to differentially regulate genes with oxidative roles in the cell. The most upregulated genes were interleukin 8 (IL-8), cytochrome P450 (CYP450), and metallothioneins (MTs), while the most downregulated genes were ribonucleotide reductases (RRs)., Conclusion: These results show that ASA modulates the expression of genes with antioxidant functions. This suggests that ASA induces a remodeling of the antioxidant microenvironment, which may in turn interfere with the replication of HCV., (© 2022 by the Association of Clinical Scientists, Inc.)

Purpose: Metformin has been widely used for the treatment of Type 2 Diabetes Mellitus (T2DM), hyperglycemia and polycystic ovarian syndrome. Recent studies have suggested the potential of this substance as a cancer chemopreventive agent. We evaluated the antitumoral effect of iRNA-PFK-1 and the combined therapy iRNA-PFK-1 + metformin in RKO p53-positive cells., Methods: mRNA levels of tumor suppressor genes AMPK, APC, and c-MYC, KRAS oncogenes were measured by qRT-PCR in RKO cells treated with 25 µM metformin alone or combined with iRNA-PFK-1, to evaluate the effect of both treatments., Results: At 72 h after treatment with either 25 µM metformin, 150 nM iRNA-PFK-1, or the combined treatment, the transcriptional levels of these biomarkers were decreased by ~73% (p˂0.05), ~99.9%, (p˂0.01), and ~76% (p˂0.05), respectively., Conclusion: These in vitro results support the potential therapeutic role of metformin and PFK-1 in the treatment of colon cancer via down-modulation of the expression of several important cancer biomarkers.