Controlled Polymer Synthesis Toward Green Chemistry: Deep Insights into Atom Transfer Radical Polymerization in Biobased Substitutes for Polar Aprotic Solvents.

Cyrene (dihydrolevoglucosenone) and its derivative Cygnet 0.0, recognized as eco-friendly alternatives to polar aprotic solvents, were utilized in atom transfer radical polymerization (ATRP) of a wide range of both hydrophobic and hydrophilic (meth)acrylates. The detailed kinetics study and electrochemical experiments of the catalytic complex in these solvents reveal the opportunities and limitations of their use in controlled radical polymerization. Both solvents produce precisely controlled polymers using supplemental activator and reducing agent (SARA) ATRP. They offer an efficient reaction medium for crafting well-defined branched architectures from naturally derived cores such as riboflavin, ß-cyclodextrin, and troxerutin, thereby significantly expanding the application scope of these solvents. Notably, Cygnet 0.0 significantly reduces side reactions between the solvent and the catalyst compared to Cyrene, allowing the catalyst complex to be used at a reduced concentration down to 75 ppm. The effective mass yield values achieved in Cyrene and Cygnet 0.0 underscore a substantial advantage of these solvents over DMF in generating processes that adhere to the principles of green chemistry. Furthermore, the copper residue in the final polymers was several hundred times lower than the permissible daily exposure to orally administered copper in pharmaceuticals. As a result, the resulting polymeric materials hold immense potential for various applications, including the pharmaceutical industry.

Common atherosclerosis genetic risk factors and subclinical atherosclerosis in rheumatoid arthritis: the relevance of disease duration.

Rheumatoid arthritis (RA) is a common systemic autoimmune disease characterized by increased cardiovascular morbidity. Several previous studies assessed associations between common atherosclerotic genetic risk factors and subclinical atherosclerosis (SA) in RA patients, yet most of them gave negative results. We undertook a cross-sectional study to evaluate the association between previously reported SNPs and subclinical atherosclerosis in a cohort of Polish RA patients. 29 SNPs associated with atherosclerosis in general population were genotyped in 289 RA patients: 116 patients with SA (increased carotid intima-media thickness and/or presence of carotid plaque) and 173 patients without SA. To assess the cumulative effect of SNPs we calculated 3 weighted genetic risk scores: GRSIMT, GRSCP and GRSCAD, comprising intima-media thickness-associated SNPs, carotid plaque-associated SNPs and coronary artery disease-associated SNPs, respectively. None of the SNPs showed a significant association with SA. However, we found an association between SA and GRSIMT. Interestingly, this association was limited to patients with short disease duration (P = 0.00004 vs. P > 0.5, for comparison of GRSIMT among patients within the 1st quartile of disease duration vs. others, respectively). Patients within the 1st quartile of disease duration were more frequently disease modifying anti-rheumatic drugs (DMARDs)-naïve and less frequently treated with biologics. Our study suggests that in patients with early RA subclinical atherosclerosis may be driven by similar genetic factors as in general population, while in long-lasting disease, the role common genetic risk factors may decrease. Possibly, this effect may be due to the influence of DMARDs.

Mild to moderate psoriasis is associated with oxidative stress, subclinical atherosclerosis, and endothelial dysfunction.

Introduction Severe psoriasis is a chronic systemic immune­mediated disease associated with increased cardiovascular (CV) risk and several comorbidities. Objectives Our aim was to assess vascular indices and selected serum biomarkers of increased CV risk in patients with nonsevere psoriasis. Patients and methods The study group included 80 patients with mild or moderate psoriasis (mean [SD] psoriasis area severity index, 18.6 [10.5]), and the control group included 39 individuals matched forage and body mass index. All patients underwent a comprehensive clinical assessment with aplanation tonometry (pulse wave velocity [PWV]), and the following ultrasound indices were measured: flowmediated dilation (FMD) and carotid intima­media thickness (IMT). Moreover, the following biomarkers were assessed in all individuals: osteoprotegerin, advanced oxidation protein products (AOPPs), visfatin, and nesfatin. Results Patients with nonsevere psoriasis had increased carotid IMT (mean [SD], 1027 [35] µm vs 587 [12] µm; P <0.05), impaired FMD (mean [SD], 16.3% [10.7%] vs 32.1% [13.7%]; P <0.001), and increased serum levels of AOPPs (mean [SD], 218.9 [44.6] µmol vs 162.1 [9.9] µmol; P <0.001) and visfatin (mean [SD], 13.1 [16.7] ng/ml vs 3.43 [1] ng/ml; P <0.001) compared with the control group. There were no significant differences in the serum levels of osteoprotegerin, nesfatin, and PWV. Oxidative stress (AOPP) was significantly associated with IMT (r = 0.3), FMD (r = -0.25), and visfatin (r = 0.6). Conclusions Our study suggests increased CV risk in patients with mild to m oderate psoriasis.

The association between 38 previously reported polymorphisms and psoriasis in a Polish population: High predicative accuracy of a genetic risk score combining 16 loci.

OBJECTIVES: To confirm the association of previously discovered psoriasis (Ps) risk loci with the disease in a Polish population and to create predictive models based on the combination of these single nucleotide polymorphisms (SNPs). MATERIAL AND METHODS: Thirty-eight SNPs were genotyped in 480 Ps patients and 490 controls. Alleles distributions were compared between patients and controls, as well as between different Ps sub-phenotypes. The genetic risk score (GRS) was calculated to assess the cumulative risk conferred by multiple loci. RESULTS: We confirmed associations of several loci with Ps: HLA-C, REL, IL12B, TRIM39/RPP21, POU5F1, MICA. The analysis of ROC curves showed that GRS combining 16 SNPs at least nominally (uncorrected P<0.05) associated with Ps (GRS-N) had significantly better discriminative power than GRS combining SNPs associated with Ps after the Bonferroni correction (AUC 0.776 vs. 0.750, P = 1 x 10-4) or HLA-C (AUC 0.776 vs. 0.694, P<1 x 10-5). On the other hand, adding additional SNPs to the model did not improve its discriminatory ability (AUC 0.782 for GRS combining all SNPs, P>0.05). In order to assess the total risk conferred by GRS-N, we calculated ORs according to GRS-N quartile - the Ps OR for top vs. bottom GRS-N quartiles was 12.29 (P<1 x 10-6). The analysis of different Ps sub-phenotypes showed an association of GRS-N with age of onset and family history of Ps. CONCLUSIONS: We confirmed the association of Ps with several previously identified genetic risk factors in a Polish population. We found that a GRS combining 16 SNPs at least nominally associated with Ps had a significantly better discriminatory ability than HLA-C or GRS combining SNPs associated with Ps after the Bonferroni correction. In contrast, adding additional SNPs to GRS did not increase significantly the discriminative power.

Carotid intima-media thickness in patients with mild or moderate psoriasis.

INTRODUCTION: Psoriasis is a chronic inflammatory disease associated with a significantly higher morbidity and various comorbidities (obesity, metabolic syndrome, diabetes). Previous studies focused mainly on patients with severe psoriasis who were found to have increased markers of early atherosclerosis, higher intima-media thickness (IMT) values. AIM: To evaluate the association between the severity or duration of psoriasis and carotid IMT in patients with mild and moderate psoriasis. MATERIAL AND METHODS: We studied seventy four patients with mild and moderate psoriasis. Clinical assessment and common carotid artery (CCA) IMT measurements were performed in all patients. RESULTS: The mean CCA IMT value was 1.03 ±0.37 mm, mean PASI score (psoriasis area severity index) was 18.6 ±10.5. There was a significant association between PASI score and IMT values (r = 0.33; p = 0.007) adjusted for age, psoriasis duration, blood pressure and smoking. However, we found no correlations between carotid IMT and disease duration or other clinical variables. CONCLUSIONS: The severity of psoriasis is associated with carotid IMT even in patients with mild and moderate psoriasis.

Long-term follow-up after radio-frequency catheter-based denervation in patients with resistant hypertension.

UNLABELLED: The aim of this single-center study was to asses the long-term clinical data of patients with resistant hypertension who underwent radiofrequency renal denervation (RND). METHODS: Out of 86 patients with resistant-hypertension, 15 pts fulfilled the study criteria for performing RND using Simplicity system by Medtronic. RESULTS: Baseline office systolic BP was 204±32.7 and diastolic BP 107.7±15.1mmHg. Baseline 24h ambulatory systolic BP was 151.8±13.9 and diastolic BP 86.8±13.8mmHg. Patients were treated with an average of 5 antihypertensive agents in maximally tolerated doses (including diuretic) during the whole trial and were followed up at 1,6,24month after RND. At every appointment an echocardiography, blood test, and blood pressure (office and ABMP) measurements were performed. The mean reduction in office systolic (SBP) and diastolic (DBP) blood pressure were the following: There were no procedural complications. All denervations were performed by experienced operator. CONCLUSIONS: We regard RND as a safe and effective procedure in resistant hypertension, although more studies and trials are needed to find the most adequate model of a patient that would be a good responder to RND.

Spindle assembly checkpoint-related failure perturbs early embryonic divisions and reduces reproductive performance of LT/Sv mice.

The phenotype of the LT/Sv strain of mice is manifested by abnormalities in oocyte meiotic cell-cycle, spontaneous parthenogenetic activation, teratomas formation, and frequent occurrence of embryonic triploidy. These abnormalities lead to the low rate of reproductive success. Recently, metaphase I arrest of LT/Sv oocytes has been attributed to the inability to timely inactivate the spindle assembly checkpoint (SAC). As differences in meiotic and mitotic SAC functioning were described, it remains obscure whether this abnormality is limited to the meiosis or also impinges on the mitotic divisions of LT/Sv embryos. Here, we show that a failure to inactivate SAC affects mitoses during preimplantation development of LT/Sv embryos. This is manifested by the prolonged localization of MAD2L1 on kinetochores of mitotic chromosomes and abnormally lengthened early embryonic M-phases. Moreover, LT/Sv embryos exhibit elevated frequency of abnormal chromosome separation during the first mitotic division. These abnormalities participate in severe impairment of preimplantation development and significantly decrease the reproductive success of this strain of mice. Thus, the common meiosis and mitosis SAC-related failure participates in a complex LT/Sv phenotype.

Accumulation and dynamics of proteins of the MCM family during mouse oogenesis and the first embryonic cell cycle.

We describe the localization of three proteins of the minichromosome maintenance (MCM) family, Mcm2, -6 and -7 in mouse ovarian oocytes. We showed that Mcm proteins are stored in two forms: soluble and insoluble. Soluble Mcm2, -6 and -7 were uniformly distributed in the nuclei of ovarian oocytes. Insoluble Mcm2 and Mcm7 (but not Mcm6) were detected in the nuclei of resting, growing and fully-grown transcribing oocytes. In transcriptionally inactive fully-grown oocytes, Mcm2 underwent redistribution and Mcm7 disappeared. A similar effect was observed when transcription in growing oocytes was inhibited with alpha-amanitin. We postulate that in mouse oogenesis, the insoluble Mcm proteins are engaged in processes related to regulation of transcription and/or chromatin organization. In oocytes preparing for meiotic maturation, aggregates of the insoluble form of Mcm2 fragmented, dispersed and ultimately disappeared from the nuclei. Numerous Mcm2-positive deposits were observed in the cytoplasm of maturing oocytes. In the one-cell embryo, insoluble Mcm2 appeared in the G1 nucleus, persisted in the S phase and was undetectable in the G2 nucleus. Such behavior of Mcm2 supports its involvement in chromatin licensing in the first embryonic cell cycle.

EMG and MMG of synergists and antagonists during relaxation at three joint angles.

The aim of the study was to estimate the influence of force changes during relaxation from maximal voluntary contraction (MVC) of elbow flexors on electrical (EMG) and mechanical (MMG) activity of synergists and antagonists at different joint angles. Repeated studies were conducted on 22 young female students to estimate the EMG and MMG activity of the biceps brachii (BB), brachioradialis (BR), and triceps brachii (TB) muscles during relaxation from MVC at an optimal angle (the angle at which a subject achieved MVC=Lo), as well as at angles that were smaller (Ls=Lo-30 degrees ) and bigger (Ll=Lo+30 degrees ). Four testing sessions consisted of 2-s or 3-s MVC at each angle with simultaneous recording of EMG and MMG signals from BB, BR, and TB muscles. The EMG/MMG probes were used to record EMG and MMG signals. The results showed that the slow relaxation rate was related to a percentage decrease of the EMG amplitude (as measured by root mean square; EMG RMS) of the synergists, while the fast relaxation was related to the EMG RMS of the antagonist, independent of the joint angle. The MMG amplitude (MMG RMS) increased gradually during slow and fast relaxation (compared to the MMG RMS at MVC), indicating a bigger muscle oscillation during relaxation; the changes were related to the muscle tested and joint angle. It was found that, during the slow relaxation, the MMG RMS reflects the force amplitude changes in the BB muscle and the velocity of force changes in the BB and TB muscle (but not in the BR). During the fast relaxation, the MMG amplitude reflects a change in muscle force in the TB and BB muscles (but not in the BR), and the velocity of force changes in the synergists (not in the antagonist). The different contribution of the force and velocity of force changes during slow and fast relaxation to the MMG signal in the three muscle tested can be related to the different deactivation time of each muscle. In conclusion, the present results indicate that MMG recordings might be useful to measure the fast relaxation of individual muscle during voluntary contraction, but this needs be tested on isolated muscle.