Many vaccine rationing guidelines urge planners to recognize, and ideally reduce, inequities. In the United States, allocation frameworks are determined by each of the Centers for Disease Control and Prevention's 64 jurisdictions (50 states, the District of Columbia, five cities and eight territories). In this study, we analyzed vaccine allocation plans published by 8 November 2020, tracking updates through to 30 March 2021. We evaluated whether jurisdictions adopted proposals to reduce inequity using disadvantage indices and related place-based measures. By 30 March 2021, 14 jurisdictions had prioritized specific zip codes in combination with metrics such as COVID-19 incidence, and 37 jurisdictions (including 34 states) had adopted disadvantage indices, compared to 19 jurisdictions in November 2020. Uptake of indices doubled from 7 to 14 among the jurisdictions with the largest shares of disadvantaged communities. Five applications were distinguished (1) prioritizing disadvantaged groups through increased shares of vaccines or vaccination appointments; (2) defining priority groups or areas; (3) tailoring outreach and communication; (4) planning the location of dispensing sites; and (5) monitoring receipt. To ensure that equity features centrally in allocation plans, policymakers at the federal, state and local levels should universalize the uptake of disadvantage indices and related place-based measures.Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are being deployed, but the global need greatly exceeds the supply, and different formulations might be required for specific populations. Here we report Day 42 interim safety and immunogenicity data from an observer-blinded, dose escalation, randomized controlled study of a virus-like particle vaccine candidate produced in plants that displays the SARS-CoV-2 spike glycoprotein (CoVLP NCT04450004 ). The co-primary outcomes were the short-term tolerability/safety and immunogenicity of CoVLP formulations assessed by neutralizing antibody (NAb) and cellular responses. Secondary outcomes in this ongoing study include safety and immunogenicity assessments up to 12 months after vaccination. Adults (18-55 years, n = 180) were randomized at two sites in Quebec, Canada, to receive two intramuscular doses of CoVLP (3.75 μg, 7.5 μg, and 15 μg) 21 d apart, alone or adjuvanted with AS03 or CpG1018. All formulations were well tolerated, and adverse events after vaccination were generally mild to moderate, transient and highest in the adjuvanted groups. There was no CoVLP dose effect on serum NAbs, but titers increased significantly with both adjuvants. After the second dose, NAbs in the CoVLP + AS03 groups were more than tenfold higher than titers in Coronavirus 2019 convalescent sera. Both spike protein-specific interferon-γ and interleukin-4 cellular responses were also induced.  https://www.selleckchem.com/products/bgb-290.html  This pre-specified interim analysis supports further evaluation of the CoVLP vaccine candidate.The basic function of β-arrestin 2 (Arrb2) is to negatively regulate the G-protein-coupled receptor signaling pathway through facilitating receptor desensitization and internalization. Arrb2 has also been reported to play various roles in cancer pathology including the proliferation, migration, invasion, metastasis, and apoptosis of solid tumors. However, the molecular mechanisms underlying the tumorigenic capacities of Arrb2 have not been elucidated. Here, we show a novel function of Arrb2 Arrb2 facilitates the degradation of HIF-1α, which is a master regulator of oxygen homeostasis. We also demonstrate that Arrb2 interacts with HIF-1α and stimulates ubiquitin-mediated 26S proteasomal degradation of HIF-1α by recruiting PHD2 and pVHL. Overexpression of Arrb2 in human glioblastoma cells suppresses HIF-1α signaling, tumor growth, and angiogenesis. Consistent with this antitumorigenic effect of Arrb2, low Arrb2 expression levels correlate with high HIF-1α expression and poor glioblastoma patient survival. These results collectively reveal a novel function of Arrb2 in the oxygen-sensing mechanism that directly regulates HIF-1α stability in human cancers and suggest Arrb2 as a new potential therapeutic target for glioblastoma.Low-intensity shockwave therapy (LiST) is an effective treatment for pain reduction in patients with Peyronie's disease (PD). We aimed to report the long-term results of a previously published randomized, sham-controlled trial on LiST for PD management. For the initial study, 102 patients with stable PD were randomly assigned to six sessions of LiST (n = 51) or sham (n = 51) therapy. All participants were subsequently contacted for an additional evaluation at 3 years after completion of the initial treatment and 63 of them (LiST = 34 and sham therapy = 29) presented for the evaluation. Among them, improvement of pain was reported in 23 participants (LiST = 16, sham = 7, p = 0.005) at 4 weeks and in 22 (LiST = 15, sham = 7, p = 0.031) at 3 years. We detected a mean difference of 2.2 points (95%CI 0.9-3.5, p = 0.002) in the visual analog pain scale at 4 weeks and a mean difference of 2.5 points (95%CI 1-4, p = 0.002) at 3 years between the two groups. No treatment-related complications occurred during the sessions or the follow-up period. Regarding the improvement of penile curvature or sexual function, no significant differences between the two groups were observed. Overall, LiST constitutes a safe and effective therapeutic approach for pain management both in the short- and long term.Frenuloplasty is a common surgical procedure performed on an outpatient basis either for the treatment of frenulum breve alone or as an additional intervention in patients undergoing circumcision. We aimed to provide tips and tricks on performing frenuloplasty, either alone or in combination with circumcision, and to generate a comprehensive review of the available literature on the matter. We suggest that the frenulum should be divided with a scalpel without the use of diathermy and reapproximated with interrupted 4-0 absorbable sutures. Moreover, the frenular artery should be maintained and any injury of the glans must be avoided to ensure optimal functional outcomes. After the procedure, a paraffin gauze filled with antibiotic paste followed by a light compression dressing for one day should be placed to maximize cosmetic results. Regarding the available literature, several methods of frenuloplasty have been described, varying from simple division of the frenulum to more sophisticated grafting or plasty techniques.