Holmesfrost0531

Focal seizures represent the most common seizure type and focal epilepsies the most common epilepsy type. Anti-seizure medications (ASMs) still represent the main form of treatment for epilepsy.

The aim of this review article is to provide an overview of available evidence about current and upcoming pharmacological options and strategies for adults with focal epilepsy focusing on the last 5years.

Seventeen drugs are currently approved for the treatment of focal seizures including cenobamate as the very latest option. Ten of these drugs are also licensed for monotherapy. Level A evidence for initial monotherapy is available for seven drugs with no robust data supporting that one drug is superior to the other. Safety, tolerability as well as pharmacoeconomic reasons would then drive treatment decisions. Data on adjunctive treatment are available for 13 ASMs showing again no obvious difference in terms of efficacy. Evidence on specific drug combinations is almost non-existent and the final decision of comb drugs and the observation period is often too short.

Saxagliptin, a member of the dipeptidyl peptidase-4 inhibitor (DPP-4i) class of drugs, was approved by the FDA for the treatment of type 2 diabetes (T2D) in 2009, and has been in clinical use for more than a decade. Since the drug was first launched, much real-world evidence has also been accumulated. The efficacy and safety of saxagliptin, especially its cardiovascular safety, are of particular interest.

This review provides an overview of the safety and efficacy of saxagliptin based on observational studies, pharmacovigilance, and meta-analyses. In addition, with the findings of recent cardiovascular outcome trials (CVOTs), the authors discuss, herein, the efficacious use of saxagliptin.

Saxagliptin exhibits a moderate glucose-lowering effect and is well tolerated by patients with T2D. this website SAVOR-TIMI 53, a CVOT of saxagliptin, reported neutral effects of saxagliptin in respect of the cardiovascular outcomes, but did raise a concern about the risk of heart failure. Conversely, recent CVOTs on sodium-glucose co-transporter-2 inhibitors (SGLT2i) have shown a favorably reduced risk of heart failure with these drugs. Also, DPP-4is decrease the serum glucagon level, whereas the SGLT2is increase it. Given the characteristics of the two classes of drugs, combined therapy with the two might be a promising option.

Saxagliptin exhibits a moderate glucose-lowering effect and is well tolerated by patients with T2D. SAVOR-TIMI 53, a CVOT of saxagliptin, reported neutral effects of saxagliptin in respect of the cardiovascular outcomes, but did raise a concern about the risk of heart failure. Conversely, recent CVOTs on sodium-glucose co-transporter-2 inhibitors (SGLT2i) have shown a favorably reduced risk of heart failure with these drugs. Also, DPP-4is decrease the serum glucagon level, whereas the SGLT2is increase it. Given the characteristics of the two classes of drugs, combined therapy with the two might be a promising option.

Aptamers provide exciting opportunities for the development of specific and targeted therapeutic approaches.

In this review, the authors discuss different therapeutic options available with nucleic acids, including aptamers, focussing on similarities and differences between them. The authors concentrate on case studies with specific aptamers, which exemplify their distinct advantages. The reasons for failure, wherever available, are deliberated upon. Attempts to accelerate the

selection process have been discussed. Challenges with aptamers in terms of their specificity and targeted delivery and strategies to overcome these are described. Examples of precise regulation of systemic half-life of aptamers using antidotes are discussed.

Despite their nontoxic nature, a variety of reasons limit the therapeutic potential of aptamers in the clinic. The analysis of adverse effects observed with the pegnivacogin/anivamersen pair has highlighted the need to screen for preexisting PEG antibodies in any clinical y efficacious molecules.

Uveitis is considered the most frequent extra-articular manifestation of Ankylosing Spondylitis (AS). Genetic factors play an important role in the pathogenesis of AS with uveitis. In this study, we investigated susceptibility genes of AS concomitant with uveitis.

First, 9p21-24 was selected as the region of susceptibility genes. Second, several candidate genes were selected from this region by bioinformatics analysis. Thirdly, a two-stage case control study was used to verify these candidate genes. The first stage included 50 AS with uveitis, 50 AS without uveitis, and 145 healthy controls. The qPCR+direct sequencing and cloning sequencing were used to identify SNPs in this stage. The second stage included 245 AS with uveitis, 360 AS without uveitis, and 530 healthy controls.

IFNA1, IFNB1, IFNA8, and IFNA13 were selected as candidate genes. In the first stage, it was found that the frequency of IFNA1 rs28383797 (G allele) and IFNA13 rs653778 (T allele) in AS with uveitis was higher than that in AS without uveitis and healthy controls. In the second stage, more samples were used to verify the two SNPs. After comprehensive data analysis in the two stages, the frequency of rs28383797 G allele and rs653778 T allele in AS with uveitis was significantly higher than that in AS without uveitis (

=1.9×10

, OR=2.161, 95%CI=1.609-2.902 and

=1.5×10

, OR=2.028, 95%CI=1.610-2.554) and healthy controls.

Rs653778 (T allele) of IFNA13 and rs28383797 (G allele) of IFNA1 were associated with AS concomitant uveitis, and may act as the susceptibility genes of AS with uveitis in the Chinese population.

Rs653778 (T allele) of IFNA13 and rs28383797 (G allele) of IFNA1 were associated with AS concomitant uveitis, and may act as the susceptibility genes of AS with uveitis in the Chinese population.The pineal gland, one of the three equivalent avian biological clock structures, is also the site of intensive neurosteroid synthesis (7α-hydroxypregnenolone and allopregnanolone). Pineal neurosteroid biosynthesis involves six enzymes cytochrome P450 side-chain cleavage - Cyp11a1 encoded, cytochrome P4507α - Cyp7b1, 3β-hydroxysteroid dehydrogenase - Hsd3b2, 5α-reductase - Srd5a1, 3α-hydroxysteroid dehydrogenase - Akr1d1, and 5β-reductase - Srd5a3. Regulation of neurosteroid biosynthesis is not fully understood; although it is known that the E4BP4 transcription factor induces activation of biosynthetic cholesterol genes, which are the targets for SREBP (element-binding protein transcription factor). SREBP principal activity in the pineal gland is suppression and inhibition of the Period2 canonical clock gene, suggesting our hypothesis that genes encoding enzymes involved in neurosteroidogenesis are under circadian clock control and are the Clock Control Genes (CCGs). Therefore, through investigation of daily changes in Cyp11a1, Cyp7b1, Hsd3b2, Akr1d1, Srd5a1, and Srd5a3, pineal genes were tested in vivo and in vitro, in cultured pinealocytes.