<p>Novel
trisubstituted ethylenes, ring-disubstituted isopropyl
2-cyano-3-phenyl-2-propenoates, RPhCH=C(CN)CO<sub>2</sub>CH(CH<sub>3</sub>)<sub>2
</sub>(where R is 2-bromo-5-methoxy, 3-bromo-4-methoxy, 5-bromo-2-methoxy, 2-chloro-3-methoxy,
3-chloro-4-methoxy, 2-chloro-6-methyl, 2-fluoro-6-methyl, 3-fluoro-2-methyl, 3-fluoro-4-methyl,
4-fluoro-2-methyl, 4-fluoro-3-methyl) were
prepared and copolymerized with styrene. The monomers were synthesized by the
piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes
and isopropyl cyanoacetate and characterized by CHN elemental analysis, IR, <sup>1</sup>H-
and <sup>13</sup>C-NMR. All the ethylenes were copolymerized with styrene in
solution with radical initiation (ABCN) at 70°C. The composition of the copolymers was
calculated from nitrogen analysis, and the structures were analyzed by IR, <sup>1</sup>H
and <sup>13</sup>C-NMR, GPC, DSC, and TGA. Decomposition of the copolymers in
nitrogen occurred in two steps, first in the 200-500ºC range with residue (1-8%
wt.), which then decomposed in the 500-800ºC range.</p>
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<p>Novel
trisubstituted ethylenes, ring-disubstituted isopropyl
2-cyano-3-phenyl-2-propenoates, RPhCH=C(CN)CO<sub>2</sub>CH(CH<sub>3</sub>)<sub>2
</sub>(where R is 2-bromo-5-methoxy, 3-bromo-4-methoxy, 5-bromo-2-methoxy, 2-chloro-3-methoxy,
3-chloro-4-methoxy, 2-chloro-6-methyl, 2-fluoro-6-methyl, 3-fluoro-2-methyl, 3-fluoro-4-methyl,
4-fluoro-2-methyl, 4-fluoro-3-methyl) were
prepared and copolymerized with styrene. The monomers were synthesized by the
piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes
and isopropyl cyanoacetate and characterized by CHN elemental analysis, IR, <sup>1</sup>H-
and <sup>13</sup>C-NMR. All the ethylenes were copolymerized with styrene in
solution with radical initiation (ABCN) at 70°C. The composition of the copolymers was
calculated from nitrogen analysis, and the structures were analyzed by IR, <sup>1</sup>H
and <sup>13</sup>C-NMR, GPC, DSC, and TGA. Decomposition of the copolymers in
nitrogen occurred in two steps, first in the 200-500ºC range with residue (1-8%
wt.), which then decomposed in the 500-800ºC range.</p>
(1) Background: Inflammation is associated with depressive illness and treatment resistance. This study assessed a novel inflammatory index, the Systemic Immune-Inflammation Index (SII), in patients diagnosed with treatment-resistant bipolar depression (TRBDD) before and after treatment with escitalopram (ESC) and celecoxib (CBX) add-on or ESC and placebo (PBO), and compared them to healthy control (HC) subjects. (2) Methods: This is a secondary biological analysis from a double-blind randomized placebo-controlled trial of CBX augmentation in TRBDD. Our subsample with available complete blood count (CBC) data included 52 TRBDD subjects, randomized into an ESC + CBX, (n = 29), an ESC + PBO arm (n = 23), and an HC group (n = 32). SII was calculated from the CBC with differential (SII = platelets x neutrophils/lymphocytes) at baseline and end of treatment (8 weeks). Blood inflammation biomarkers, growth factors, and kynurenine metabolites were determined at both timepoints. Depressive symptom severity was the primary outcome, using the HAMD-17 rating scale score to quantitate treatment response and remission rates. (3) Results: Baseline SII did not discriminate TRBDD from HC, nor was it associated with HAMD-17 score at any timepoint, although it was significantly associated with lower baseline VEGF (p = 0.011) and higher week 8 levels of IL1-β (p = 0.03) and CRP (p = 0.048). Post-treatment HAMD-17 was not independently predicted using baseline SII unless an interaction with age was present (p = 0.003 was included), even after relevant adjustments. A similar effect was seen with baseline neutrophils. (4) Conclusions: While SII was not an independent predictor of treatment outcome, elevated baseline SII was a predictor of poor treatment response amongst older patients with TRBDD.
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