Robust antibody response after a third BNT162b2 vaccine compared to the second among immunocompromised and healthy individuals,a prospective longitudinal cohort study

PurposeAs protection from COVID-19 following two doses of the BNT162b2 vaccine showed a time dependent waning, a third (booster) dose was administrated. This study aims to compare the antibody response following the third dose versus the second and to evaluate post-booster seroconversion.MethodsA prospective observational study conducted in Maccabi Healthcare Services. Serial SARS-CoV-2 Spike IgG tests, 1,2,3 and 6 months following the second vaccine dose and one month following the third were obtained. Neutralizing antibody levels were measured in a subset of participants. Per individual SARS-CoV-2 Spike IgG titer ratios were calculated one month after the booster administration compared to titers one month following the second dose and prior to booster.ResultsAmong 110 participants, 56 (51%) were women. Mean age was 61.7 ± 1.9 years and 66 (60%) were immunocompromised. One month after third dose, IgG titers were induced 7.83 (95 %CI 5.25–11.67) folds and 2.40 (95 %CI 1.90–3.03) folds compared to one month after the second, in the immunocompromised and immunocompetent groups, respectively. Of the 17 immunocompromised participants who were seronegative after the second dose, 4 (24%) became seropositive following the third. Comparing the titers prior to the third dose, an increase of 50.7 (95 %CI 32.5–79.1) fold in the immunocompromised group and 25.7 (95 %CI 19.1–34.7) fold in and immunocompetent group, was observed.ConclusionA third BNT162b2 vaccine elicited robust humoral response, superior to the response observed following the second, among immunocompetent and immunocompromised individuals.     

Sofosbuvir-velpatasvir en pacientes mexicanos con hepatitis C: una revisión retrospectiva

IntroductionThe sofosbuvir-velpatasvir (SOF/VEL) combination is a direct-acting antiviral therapy that is authorized and available in Mexico, making the performance of a real-world multicenter study that evaluates the sustained virologic response at 12 weeks post-treatment a relevant undertaking.MethodsA retrospective review of the case records of 241 patients seen at 20 hospitals in Mexico was conducted to assess hepatitis C treatment with the SOF/VEL combination (n = 231) and the sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) combination (n = 10). The primary efficacy endpoint was the percentage of patients that achieved SVR at 12 weeks after the end of treatment.ResultsOverall SVR was 98.8% (95% CI 97.35-100%). Only three patients did not achieve SVR, two of whom had cirrhosis and a history of previous treatment with peg-IFN. Of the subgroups analyzed, all the patients with HIV coinfection, three patients with genotype 3, and the patients treated with the SOF/VEL/RBV combination achieved SVR. The subgroups with the lower success rates were patients that were treatment-experienced (96.8%) and patients with F1 fibrosis (95.5%). The most frequent adverse events were fatigue, headache, and insomnia. No serious adverse events were reported.ConclusionTreatments with SOF/VEL and SOF/VEL/RBV were highly safe and effective, results coinciding with those of other international real-world studies.     

Single-dose replicating poxvirus vector-based RBD vaccine drives robust humoral and T cell immune response against SARS-CoV-2 infection

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Evaluation of prime and prime-boost immunization strategies in BALB/c mice inoculated with Leishmania infantum transfected with toxic plasmids

The etiologic agents of visceral leishmaniasis are Leishmania infantum and Leishmania donovani. Despite the variety of drugs available to treat leishmaniasis, most lead to serious adverse effects, and resistance to these drugs has been reported. Currently, no leishmaniasis vaccine is available for humans. That is why the group developed transgenic L. infantum promastigote lines, which express toxic proteins after differentiation into amastigotes. That is why group developed the pFL-AMA plasmid and transfected it into L. Infantum promastigotes. This plasmid was expressed only in the amastigote form of the parasite. Sequences encoding toxic proteins (active bovine trypsin and egg avidin) were inserted in this plasmid, and the transfected parasites died after the differentiation process. In this study, two immunization protocols were performed in BALB/c mice: prime and prime-boost immunization prior to challenge with the wild-type L. infantum (WT). The parasite burdens in the spleen, liver, and bone marrow were evaluated to verify immunological protection. Histopathological analysis of the spleen and liver and the humoral immune response were also performed. The data showed that the parasite burden was reduced in prime-boosted mice in the spleen, liver, and bone marrow, indicating that mice immunized with two doses of the transfected parasites were satisfactorily protected. High levels of IgG, IgG1, and IgG2a antibodies were observed, as well as the presence of anti-inflammatory cytokine Interleukine-10 and pro-inflammatory cytokine Tumor Necrosis Factor-α (TNF-α) and Interferon-γ (IFN – γ) suggesting a Th1/Th2 mix response, in addition to the presence of multinucleated giant cells in the spleen and lymphocyte infiltration in the liver. Therefore, L. infantum transfected with a toxic plasmid is an excellent vaccine candidate against visceral leishmaniasis and the application of a boost before the challenge promotes greater protection against WT L. infantum infection.     

DNA损伤应答缺陷作为乳腺癌治疗靶点的研究进展

DNA损伤应答（DNA damage response,DDR）缺陷是近年来乳腺癌治疗研究的热门靶点之一。DDR通路负责DNA损伤后的识别、信号转导和修复,其功能异常可导致细胞的凋亡或基因组不稳定性的增加。目前进入临床研究阶段的乳腺癌DDR靶向药物主要包括多聚腺苷二磷酸核糖聚合酶[poly (ADP-ribose) polymerase,PARP]抑制剂、ATM抑制剂、CHEK1抑制剂、ATR抑制剂及WEE1抑制剂等。主要从DDR缺陷的概念、以DDR作为靶点的基本原理、DDR各类靶向药物的临床研究现状及其在临床应用中的难点与挑战等方面展开综述。     

Pan-cancer proteomic map of 949 human cell lines

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Return to sport and beyond following intramuscular tendon hamstring injury: A case report of an English Premier League football player

BackgroundHamstring strain injuries are the most common type of injury in elite football and are associated with a high risk of reinjury, particularly those involving the intramuscular tendon (IMT). Limited information is available regarding the rehabilitation and return to sport (RTS) processes following such injuries. This case study describes the clinical presentation of an elite football player following IMT hamstring injury, their on- and off-pitch rehabilitation alongside performance monitoring throughout RTS and beyond.Case scenarioAn elite football player suffered a grade 2c hamstring injury during an English Premier League (EPL) match. The player underwent early post-injury management, alongside progressive off-pitch physical preparation. The ‘control-chaos continuum’ was used as a framework for on-pitch rehabilitation to prepare the player for a return to full team training and competition. Objective and subjective markers of the player's response to progressive on- and off-pitch loading were monitored throughout RTS and beyond.OutcomesThe player returned to on-pitch rehabilitation after 11 days, to full team training having achieved weekly pre-injury chronic running load outputs after 35 days and played in the EPL 40 days post-injury. The player did not suffer reinjury for the rest of the EPL season.ConclusionAn understanding the unique structural and mechanical properties of the IMT, alongside expected RTS timeframes are important to inform rehabilitation and decision-making processes post-injury. Performance and frequent load-response monitoring throughout RTS and beyond, in conjunction with practitioner experience and effective communication are critical in facilitating effective RTS and reduce risk of reinjury following IMT injury.