The race for clinical trials on Omicron-based COVID-19 vaccine candidates: Updates from global databases.

The coronavirus disease 2019 (COVID-19) has caused more than 6.5 million deaths globally as of June 10, 2022. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) has the greatest transmission rate and can cause hospitalization in vaccinated individuals. It has been the most distinct SARS-CoV-2 variant of concern to date. The existing inactivated vaccines made with the wild-type strain are less efficient to prevent disease and/or hospitalization associated with the Omicron variant, even after a booster dose. Hence, it is crucial to develop new vaccines that are effective against this variant. The objective of this study was to summarize the data on existing clinical trials for new COVID-19 vaccines formulated against Omicron variant. Clinical trials from the international clinical trials registry platforms were searched and analyzed. As of June 10, 2022, a total of 15 clinical trials are available consisting of six and nine clinical trials of inactivated and messenger RNA (mRNA)-based vaccine candidates containing the Omicron variant, respectively. Those trials are evaluating four inactivated and four mRNA-based vaccine candidates. Although Omicron-specific vaccines are highly desired, their development is challenging since the SARS-CoV-2 variant formation is still unpredictable. Although two vaccines from Pfizer and Moderna have been approved for emergency use in the US and the UK for Omicron variant, the Asian pharmaceutical companies such as CNBG (Sinopharm), Sinovac, and Shifa Pharmed also have Phase 3 clinical trials under development and almost all clinical trials are expected to be completed in 2023. These results should help guide academics and policymakers in the COVID-19 vaccine field regarding investments in updated booster doses against the SARS-CoV-2 Omicron variant.

Propuesta algoritmo de cribado para alteraciones morfológicas de la Próstata. Revisión de la evidencia actual / Proposed screening algorithm for morphological alterations of the Prostate. Review of current evidence

Las alteraciones morfológicas de la próstata, por las que se realiza cribado son la hiperplasia prostática benigna (HPB) y el cáncer de próstata (CaP). La HPB es el tumor benigno más frecuente en varones mayores de 50 años, se caracteriza por el aumento del volumen de la glándula y usualmente acompañado de síntomas urinarios. El CaP es la segunda causa de muerte relacionada con cáncer en Estados Unidos y Europa en mayores de 70 años, su incidencia por debajo de los 50 es rara. El cribado o pruebas de detección, tiene como meta el hallar el cáncer antes de la aparición de síntomas, el cribado no se realiza en pacientes por sospechar que tienen cáncer, sino como un método de pesquisa. El objetivo de este artículo, es efectuar una revisión a los referentes teóricos, y proponer un nuevo algoritmo diagnóstico de alteraciones morfológicas de la próstata, basado en la evidencia.

Morphological alterations of the prostate, for which screening is performed include benign prostatic hyperplasia (BPH) and prostate cancer (PCa). BPH is the most common in men over 50 years benign tumor, is characterized by the increase in the volume of the gland and usually accompanied by urinary symptoms. PCa is the second leading cause of cancer-related death in the United States and Europe in over 70 years, the incidence below 50 is rare. Screening or testing, aims the finding cancer before the onset of symptoms, screening is not performed in patients with suspected cancer, but as a method of investigation. The purpose of this article is to review the theoretical framework and propose a new diagnostic algorithm of morphological alterations of the prostate, based on evidence.

[The mechanism of antiarrhythmic action of the endogenous ORL1 receptor agonist nociceptin]. / K mekhanizmu aniaritmicheskogo deistviia éndogennogo agonista ORL! retseptorov Notsitseptina.

Prophylactic intravenous (i.v.) injections of a selective agonist of ORL1 receptors nociceptin (orphanin FQ) in a dose of 0.4 mg/kg prevented the development of aconitine-induced arrhythmia in rats narcotized with diethyl ether or chloralose. Pretreatment with L-NAME (50 mg/kg) completely abolished this effect of orphanin FQ, while the pretreatment with indomethacin (10 mg/kg) only attenuated the agonist effect, rather than abolished it completely. At the same time, pretreatment with hexamethonium (10 mg/kg) or glibenclamide (3 mg/kg) had no effect on the nociceptin-dependent cardiac tolerance to the arrhythmogenic action of aconitine. Intracerebroventricular (i.c.v.) infusion of orphanin FQ (36 microg) also prevented the onset of aconitine-induced arrhythmia, but this effect was completely abolished by hexamethonium. It is concluded that the antiarrhythmic action of nociceptin with respect to aconitine-induced arrhythmia upon i.v. and i.c.v. administration is explained by different mechanisms. In the former case, the effect of orphanin FQ is related to the activation of NO synthase and cyclooxygenase, while the central action involves the vegetative nervous system.

[Role of ORL1 receptors in the regulation of cardiac resistance to arrhythmogenic effects ]. / O znachenii ORL1-retseptorov v reguliatsii ustoichivosti serdtsa k aritmogennym vozdeistviiam.

It has been found that intravenous administration of nociceptin (0.4 mg/kg) prevents development of aconitine-induced arrhythmias but has no effect on the incidence of occlusion, reperfusion, CaCl2-induced arrhythmias, and exacerbates epinephrine-evoked dysrhythmias. Pretreatment with hexamethonium, atropine, guanethidine and naloxone did not abolish the arrhythmic effect of nociceptin. Intracerebroventricular infusion of orphanin FQ was shown to increase cardiac tolerance of arrhythmogenic influence of aconitine, but this effect is completely abolished by hexamethonium administration. It has been suggested that stimulation of both central and peripheral ORL1 receptors increases cardiac resistance against arrhythmogenic effect of aconitine via different mechanisms.

Characterisation and comparison of novel ligands for the nociceptin/orphanin FQ receptor.

Studies of nociceptin/orphanin FQ (NC) have been hampered by the paucity of available ligands with activity at the nociceptin receptor (NCR). In this study we have compared the agonist profile of NC and a novel NCR agonist, Ro65-6570, in a series of radioligand binding studies and effects on forskolin-stimulated cAMP formation in Chinese hamster ovary (CHO) cells expressing the recombinant human NCR (CHOhNCR). In addition, we report the effects of three antagonists, [Nphe1]NC(1-13)NH2, J-113397 and III-BTD, on these responses. In radioligand binding studies Ro65-6570, [Nphe1]NC(1-13)NH2, J-113397 and III-BTD displaced [3H]NC with similar pKi values (8.4-8.8). This compares with a pK(D) of 10.2 for NC in a direct saturation experiment. [Nphe1]NC(1-13)NH2 and J-113397 showed at least 100-fold selectivity over classical opioid receptors. Both NC and Ro65-6570 produced a concentration-dependent inhibition of cAMP formation with pEC50 values of 9.56+/-0.06 and 8.68+/-0.04, respectively. Maximum inhibition achieved was 100%. [Nphe1]NC(1-13)NH2, J-113397 and III-BTD produced a parallel rightward shift in the concentration-response curves to both NC and Ro65-6570 with pK(B) values of approximately 6.5, approximately 7.5 and approximately 7.7, respectively. Importantly, all three antagonists were devoid of residual agonist activity. Collectively, these data indicate the value of Ro65-6570, [Nphe1]NC(1-13)NH2, J-113397 and III-BTD in studies of the physiological role played by NC. However, due to the relatively poor selectivity of Ro65-6570 and III-BTD caution should be exercised when using tissues that co-express micro-opioid receptors.