Graycrowley3932

Introduction Dual antiplatelet therapy (DAPT) is required for coronary artery disease treated with drug-eluting stents (DES) implantation. Shortening DAPT duration would be beneficial for patients with high bleeding risk.Areas covered Early healing patterns, especially stent strut coverage, assessed by optical coherence tomography (OCT) as a surrogate of neointima have been investigated to make decisions on whether short DAPT would be a safe alternative. This review evaluates the OCT evidence (i.e. neointimal coverage of stent struts within 3 months) for shortening DAPT duration after DES implantation.Expert commentary Shortening DAPT (i.e. within 3 months) duration after DES implantation might reduce complications including bleeding without increasing stent thrombosis. However, the optimal duration of DAPT after DES implantation is under discussion. Long-term assessment of short DAPT is required for the decision of the new guidelines regarding the recommended duration of DAPT.Background/objectives This study aims to analyze the positive outcomes observed in cardiovascular outcomes trials conducted with sodium-glucose co-transporter inhibitors and determine their statistical and clinical significance.Methods A literature search conducted using the Cochrane library resulted in five citations - randomized controlled trials (RCTs), identified for analysis. Positive cardio-renal outcomes from the five RCTs were analyzed in accordance with a pre-defined strategy which included the hierarchical flow chart, presence of a persuasive p-value (p  less then  0.001), and number needed to treat (NNT) estimation calculated from the absolute risk reduction (ARR) reported.Results Only four instances fulfilled these stringent criteria - reduction of cardiovascular (CV) death with empagliflozin in T2DM patients with established atherosclerotic cardiovascular disease (eASCVD) (p  less then  0.001; NNT 45), reduction in cardiorenal outcomes with canagliflozin in a pooled T2DM population with macroalbuminuria (p  less then  0.00001; NNT 22), as well as reduction in the composite of CV death or hospitalization for heart failure (hHF) (p  less then  0.001; NNT 30) and also reduction in hHF or CV death with dapagliflozin in T2DM with heart failure with reduced ejection fraction (HFrEF) (p  less then  0.001; NNT 21).Conclusions Statistically positive outcome results must be interpreted in the context of associated clinical benefits and not in isolation.Introduction Pharmaceutical research and development (R&D) is costly and only a minority of patients can access innovative medicines due to affordability constraints. Value-added medicines (VAMs) can offer potential benefits at significantly lower R&D costs.Areas covered VAMs may address different health care needs and problems, including off-label use of medicines, poor patient adherence, problems related to polypharmacy, need for home and/or personalized health care services. However, several barriers prevent societies from maximizing the benefits of incremental innovation related to VAMs. Generic manufacturers have limited budget and experience to demonstrate the value of new VAMs. Current market exclusivity options do not efficiently exclude freeridership and do not guarantee a return on investment for VAM innovators. Value propositions of VAMs are limitedly consistent with current HTA frameworks, consequently, incremental innovation is not acknowledged, nor rewarded with differential pricing by payers. Moreover, VAMs are often perceived solely as generic medicines by prescribers.Expert opinion Current practices may need to be reconsidered to exploit the full societal benefit of VAMs, including more efficient policies to guarantee market exclusivity for incremental innovation, acknowledgment of a fair price premium based on a specific value framework and the acceptance of low-cost evidence generation methods.The pathogenesis of systemic lupus erythematosus (SLE) is characterised by the hyper-activation of immunologic pathways related to the antiviral response. beta-catenin signaling Exogenous and endogenous retroviruses, by integrating their DNA templates in the host cell genome, may epigenetically control the transcription of genes involved in the immune response. Furthermore, their nucleic acids or neo-synthesized proteins could stimulate the sensor molecules placed upstream the inflammatory cascade. Exogenous retroviruses, like human immunodeficiency virus, have been associated to SLE-like manifestations or to a fair SLE diagnosis. In addition, there is some evidence confirming a pathogenic role of human endogenous retroviruses in SLE. In line with these data, the use of antiretroviral agents could represent an attractive opportunity in the future therapeutic algorithms of this disease, but studies are still missing.N6-methyladenosine (m6A) RNA methylation has become a progressively popular area of molecular research since the discovery of its potentially essential regulatory role amongst eukaryotes. m6A marks are observed in the 5'UTR, 3'UTR and coding regions of eukaryotes and its mediation has been associated with various human diseases, RNA stability and translational efficiency. To understand the implications of m6A methylation in molecular governance, its functionality and mechanism must be initially understood. m6A regulation through its readers, writers and erasers as well as an insight into the potential "cross-talk" occurring between m6A and previously well documented regulatory molecular mechanisms have been characterized. The majority of research to date has been limited to few species and has yet to explore the species- and tissue specific nature or mechanistic plasticity of m6A regulation. There is still a tremendous gap in our knowledge surrounding the mechanism and functionality of m6A RNA methylation. Here we review the formation, removal, and decoding of m6A amongst animals, yeast, and plants while noting potential "cross-talk" between various mechanisms and highlighting potential areas of future research.Introduction Palmoplantar pustulosis, or pustulosis palmaris et plantaris (PPP), is a chronic, recurrent inflammatory skin disease that is sometimes unresponsive to conventional therapy. The anti-interleukin 23 antibody guselkumab is effective for treating PPP.Areas covered This review details the current understanding of PPP and discusses why guselkumab may be effective. Guselkumab is only approved for the treatment of PPP in Japan. In the United States, Canada, the European Union, and several other countries, it is approved for the treatment of moderate-to-severe plaque psoriasis, but not for PPP. Furthermore, guselkumab was approved only 1 year ago; its efficacy will be proven only by phase 2 and 3 clinical trials.Expert opinion The first double-blinded randomized placebo-controlled trial (RCT) of guselkumab for PPP has been completed. The drug was effective, and guselkumab could be used as a new agent for PPP treatment, in addition to several conventional therapeutics. However, several issues remain. For example, there is no mouse model of PPP, so careful observation of human PPP patients and establishment of a good experimental PPP model are essential.Orthosiphon stamineus (O.S) is widely consumed for its medidcinal value including anti-inflammatory, anti-infective, and diuretic properties. The present study evaluates the cytoprotective, anti-mutagenic, and anticlastogenic efficacies of standardized extract of Orthosiphon stamineus. Normal liver cell line (WRL68) exposed to hydrogen peroxide and serum-deprived media as insults to evaluate cytoprotective and glutathione activation activities of (Et. O. s). Salmonella typhimurium TA98 and TA100 exposed to different concentrations of (Et. O. s). The influence of Et. O. s on mitotic, replicative indices as well as chromosomal aberration (CA) and sister chromatid exchange (SCE) induced in human peripheral blood lymphocytes by mitomycin C (MMC). The Et. O.s proved to be a potent scavenger for hydrogen peroxide and other free radicals in serum-depraved media, which showed to stimulate glutathione production in liver cells line. Moreover, it did not induce mutations in S. typhimurium subspecies TA98 and TA100. The standardized extract exhibited powerful antimutagenic activities as verified against both 2-nitrofluorene and sodium azide in S. typhimurium TA98 and TA100 cells, respectively. Cytogenetic tests showed high concentrations of Et. O. s to reduce the values of mitotic and replicative indices without any accompanying side effects, such as chromosomal abnormalities or SCE. To ameliorate MMC effects, pretreatment with the extract proofed to be efficient protocol. These data suggests that O. stamineus extract could be useful as cytoprotective, antimutagenic, and anticlastogenic efficacies, which owes to its potent chemoprevention, antioxidant, and glutathione activation properties.Novel 3(2H)-pyridazinone derivatives were designed, synthesised in satisfactory yields and evaluated in different experimental assays to assess their preliminary toxicity in vivo and anti-proliferative effects against HCT116 cell lines in vitro. Artemia salina lethality test provided LC50 values >100 µg/mL for all compounds. Successive assays revealed that some compounds were endowed with a promising anti-proliferative effect against HCT116 cells, alone or stimulated by serotonin as a pro-inflammatory factor in order to mimick an inflamed model in vivo of cancer cell microenvironment. Moreover, the kinurenic acid level after treatment with these newly synthesised compounds was monitored as a marker of anti-proliferation in colon carcinoma models. The IC50 values obtained for the best-in-class compounds were comparable to that of daunorubicin as a reference drug. Conversely, these compounds were not able to counteract the spontaneous migration of human cancer HCT116 cell line in the wound healing paradigm.Reactive Skin Decontamination Lotion (RSDL®) is an FDA-approved skin decontamination kit carried by service members for removal and neutralisation of vesicants and nerve agents. The RSDL kit, comprised of a lotion-impregnated sponge, was shown to be the superior medical decontamination device for chemical warfare agent (CWA) exposure on intact skin. In the event of a chemical exposure situation (i.e. terrorism, battlefield) physical injuries are probable, and preservation of life will outweigh the risk associated with application of RSDL to compromised skin. The purpose of this study was to quantify the rate and quality of wound healing in epidermal skin wounds treated with RSDL in a porcine model. Degree of wound healing was assessed using bioengineering methods to include ballistometry, colorimetry, evaporimetry, and high-frequency ultrasonography. Clinical observation, histopathology and immunohistochemistry were also utilised. All pigs received four bilateral superficial abdominal wounds via a pneumatic dermatome on their ventral abdomen, then were treated with the following dressings over a seven-day period RSDL sponge, petroleum based Xeroform® gauze, 3 M™ Tegaderm™ Film, and 3 M™ Tegaderm™ Foam. Two additional non-wounded sites on the flank were used as controls. Two groups of pigs were then evaluated for a 21- or 56-day time period, representing short- and long-term wound-healing progression. Our findings indicated RSDL had a negative impact on wound-healing progression at both 21 and 56 days post-injury. Wounds receiving RSDL demonstrated a decreased skin elasticity, significant transepidermal water loss, and altered skin colouration and thickness. In addition, the rate of wound healing was delayed, and return to a functional skin barrier was altered when compared to non-RSDL-treated wounds. In conclusion, wound management care and clinical therapeutic intervention plans should be established to account for a prolonged duration of healing in patients with RSDL-contaminated wounds.