Impact of SARS‐CoV‐2 Mu variant on vaccine effectiveness: a comparative genomics study at the peak of the third wave

alexandrossfakianakis shared this article with you from Inoreader Impact of SARS‐CoV‐2 Mu variant on vaccine effectiveness: a comparative genomics study at the peak of the third wave in Bogota, Colombia Via Journal of Medical Virology Abstract We assessed the circulation of SARS-CoV-2 variants amongst vaccinated military personnel in Bogotá, Colombia to evaluate the mutations of certain variants and their potential for breakthrough infection in vaccinated subjects. We observed that in vaccinated individuals the most frequent infecting lineage was Mu (B.1.621 and B.1.621.1). The above possibly associated with specific mutations that confers it with vaccine-induced immune escape ability. Our findings highlight the importance of how genomic tracking coupled with epidemiological surveillance can assist in the study of novel emerging variants (e.g. Omicron) and their impact on vaccination efforts worldwide. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cell pyroptosis in picornavirus and its potential for treating viral infection

alexandrossfakianakis shared this article with you from Inoreader Cell pyroptosis in picornavirus and its potential for treating viral infection Via Journal of Medical Virology Abstract Cell pyroptosis has received increased attention due to the associations between innate immunity and disease, and it has become a major focal point recently due to in-depth studies of cancer. With increased research on pyroptosis, scientists have discovered that it has an essential role in viral infections, especially in the occurrence and development of some picornavirus infections. Many picornaviruses, including Coxsackievirus, a71 enterovirus, human rhinovirus, encephalomyocarditis virus, and foot-and-mouth disease virus induce pyroptosis to varying degrees. This review summarized the mechanisms by which these viruses induce cell pyroptosis, which can be an effective defense against pathogen infection. However, excessive inflammasome activation or pyroptosis also can damage the host's health or aggravate disease progression. Careful approaches that acknowledge this dual effect will aid in the exploration of picornavirus infections and the mechanisms that produce the inflammatory response. This information will promote the development of drugs that can inhibit cell pyroptosis and provide new avenues for future clinical treatment. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

T cell responses to SARS‐CoV‐2 Omicron spike epitopes with mutations after the third booster dose of an inactivated vaccine

alexandrossfakianakis shared this article with you from Inoreader T cell responses to SARS‐CoV‐2 Omicron spike epitopes with mutations after the third booster dose of an inactivated vaccine Via Journal of Medical Virology Abstract The rapidly spreading SARS-CoV-2 Omicron variant contains more than 30 mutations that mediate escape from antibody responses elicited by prior infection or current vaccines. Fortunately, T cell responses are highly conserved in most individuals, but the impacts of mutations are not clear. Here, we showed that the T cell responses of individuals who underwent booster vaccination with CoronaVac were largely protective against the SARS-CoV-2 Omicron spike protein. To specifically estimate the impact of Omicron mutations on vaccinated participants, 16 peptides derived from the spike protein of the ancestral virus or Omicron strain with mutations were used to stimulate peripheral blood mononuclear cells (PBMCs) from the volunteers. Compared with the administration of two doses of vaccine, booster vaccination substantially enhanced T cell activation in response to both the ancestral and Omicron epitopes, although the enhancement was slightly weakened by the Omicro n mutations. Then, the peptides derived from these spike proteins were used separately to stimulate PBMCs. Interestingly, compared with the ancestral peptides, only the peptides with the G339D or N440K mutation were detected to significantly destabilize the T cell response. Although more participants need to be evaluated to confirm this conclusion, our study nonetheless estimates the impacts of mutations on T cell responses to the SARS-CoV-2 Omicron variant. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Coinfection of leptospirosis and Coronavirus disease 2019: a retrospective case series from a coastal region in South India

alexandrossfakianakis shared this article with you from Inoreader Coinfection of leptospirosis and Coronavirus disease 2019: a retrospective case series from a coastal region in South India Via Journal of Medical Virology Abstract Introduction During the monsoon season of 2020, the coastal areas of South India were endemic to both Leptospirosis and COVID-19. This study aimed to investigate the clinical features and outcomes of patients infected with both infections. Methodology A retrospective review of charts of all patients with COVID-19 who were also diagnosed with leptospirosis by IgM ELISA was undertaken. The clinical features, laboratory report, treatment details and outcomes of all the included patients were recorded. The collected data were summarised as the frequency with percentage for categorical data and the mean or median for continuous data. Results Twenty four cases of coinfections were admitted between July and November 2020. Most of these patients were categorised as severe COVID-19 (n=15, 62.5%). Acute Kidney Injury was seen in 79.2% (n=19) patients, while raised bilirubin was present in 79.2% (n=19) of the patients. All patients had raised CRP, while al l but one had raised procalcitonin. Thrombocytopenia, leucocytosis and leukocytopenia were seen in 91.7% (n=22), 45.8% (n=11) and 12.5% (n=3) of the patients. The median duration of hospital stay was 11 (8.25-15) days. A total of 79.2% (n=19) of the patients improved and were discharged, while 20.8% (n=5) died during the hospital stay. Conclusion Patients with fever and atypical manifestations such as hepatic dysfunction, renal dysfunction, and thrombocytopenia should be evaluated for leptospirosis even if they are COVID positive. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Low Body Mass Index at Treatment Initiation and Rifampicin-Resistant Tuberculosis Treatment Outcomes: An Individual Participant Data Meta-Analysis

alexandrossfakianakis shared this article with you from Inoreader Low Body Mass Index at Treatment Initiation and Rifampicin-Resistant Tuberculosis Treatment Outcomes: An Individual Participant Data Meta-Analysis Via Clinical Infectious Diseases Advance Access Abstract Background The impact of low body-mass-index at treatment initiation on rifampicin-resistant tuberculosis treatment outcomes is uncertain. We evaluated the association between body-mass-index at rifampicin-resistant tuberculosis treatment initiation and end-of-treatment outcomes, and its modifying factors. Methods We did an individual participant data meta-analysis of adults ≥18 years with rifampicin-resistant tuberculosis whose body-mass-index was documented at treatment initiation. We compared odds of any unfavorable treatment outcome, mortality, or failure/recurrence between patients who were underweight (body-mass-index <18.5 kg/m2) and not underweight. Adjusted odds ratios and 95%CI were estimated using logistic regression, with matching on demographic, clinical, and treatment-related factors. We evaluated effect modification by HIV-infection and other variables using likelihood ratio tests. In secondary an alysis, we estimated cumulative incidence of mortality during treatment, stratified by HIV-infection. Results Overall, 5148 patients were included; 1702 (33%) were underweight at treatment initiation. The median (IQR) age was 37 years (29 to 47) and 455 (9%) were living with HIV. Compared to non-underweight patients, the adjusted odds ratio among underweight patients was 1.7 (95%CI 1.4-1.9) for any unfavorable outcome, 3.1 (2.4-3.9) for death, and 1.6 (1.2-2.0) for failure/recurrence. Significant effect modification was observed for WHO region where the participant was treated. Among patients without HIV, cumulative incidence of 24-month mortality 14.8% (95%CI 12.7%-17.3%) for underweight and 5.6% (4.5%-7.0%) for not underweight patients. Among patients living with HIV, corresponding values were 33.0% (25.6%-42.6%) and 20.9% (14.1%-27.6%). Conclusions Low body-mass-index at treatment initiation for rifampicin-resistant tuberculosis is associated with increased odds of unfavorable treatment outcome, particularly mortality. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Characterizing HIV-preventive, plasma tenofovir concentrations. A pooled participant-level data analysis from HIV pre-exposure prophylaxis (PrEP) clinical trials.

alexandrossfakianakis shared this article with you from Inoreader Characterizing HIV-preventive, plasma tenofovir concentrations. A pooled participant-level data analysis from HIV pre-exposure prophylaxis (PrEP) clinical trials. Via Clinical Infectious Diseases Advance Access Abstract Background Daily dosing of tenofovir disoproxil fumarate (TDF), with or without emtricitabine (FTC), has high efficacy in preventing HIV infection when individuals are adherent. The target protective plasma concentration of tenofovir (TFV), however, is not fully understood. The aim of this study is to estimate the protective TFV plasma concentration. Methods Participant data from TFV-based daily oral and topical active arms of phase III trials (iPrEx, VOICE and Partners PrEP) were pooled (n = 2,950). Individual specific risk scores (low and high risk) of acquiring HIV, based on an earlier placebo analysis, were created. Longitudinal TFV pharmacokinetics (PK), HIV outcome, individual risk scores and the effect of sex at birth data were integrated and analyzed using non-linear mixed effects models (NONMEM). Results Around 50% of the individuals were estimated to be adherent, which differed from self-reported adherenc e (∼90%) and large variation between longitudinal adherence patterns were identified. Following oral administration, the estimated protective TFV trough concentration was substantially higher in high risk females (45.8 ng/mL) compared to high risk males (16.1 ng/mL) and to low risk individuals (∼7.5 ng/mL). Dosing simulations indicated that high risk women require full adherence to maintain protective levels. Conclusions Using the largest PK-HIV outcome database to date, we developed a population adherence-PK-risk-outcome model. Our results indicate that high risk females need higher levels of plasma TFV to achieve HIV protection compared to males. HIV protection exceeds 90% in all populations if daily adherence is achieved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effectiveness of mRNA-based vaccines during the emergence of SARS-CoV-2 Omicron variant

alexandrossfakianakis shared this article with you from Inoreader Effectiveness of mRNA-based vaccines during the emergence of SARS-CoV-2 Omicron variant Via Clinical Infectious Diseases Advance Access Abstract Background We evaluated effectiveness of mRNA-based vaccines following emergence of SARS-CoV-2 Omicron variant. Methods Recipients of a third dose of BNT162b2 or mRNA-1273 ≥ 180 days after the primary series were matched to primary series recipients and unvaccinated persons. Participants were followed from December 1, 2021 to March 12, 2022. Outcomes were documented SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 death. Effectiveness was calculated from 100-day risks estimated with the Kaplan-Meier estimator. Results BNT162b2 and mRNA-1273 groups respectively included 221,267 and 187,507 third dose recipients matched to equal numbers of primary series recipients and unvaccinated persons. Compared to no vaccination, effectiveness of a third dose of BNT162b2 was 47.8% (95% confidence interval [CI]: 45.2-50.3), 81.8% (95% CI 79.2-84.2), and 89.6% (95% CI 85.0-93.6) against documented infection, hospitalizat ion, and death, respectively. Effectiveness of a third dose of BNT162b2 compared to the primary series was 30.1% (95% CI 26.2-33.7), 61.4% (95% CI 55.0-67.1), and 78.8% (95% CI 67.9-87.5) against documented infection, hospitalization, and death, respectively.Effectiveness of a third dose of mRNA-1273 compared to no vaccination was 61.9% (95% CI 59.4-64.4), 87.9% (95% CI 85.3-90.2), and 91.4% (95% CI 86.4-95.6) against documented infection, hospitalization, and death, respectively. Effectiveness of a third dose of mRNA-1273 compared to the primary series was 37.1% (95% CI 32.2-41.7), 63.5% (95% CI 53.7-71.6), and 75.0% (95% CI 55.4-88.0) against documented infection, hospitalization, and death, respectively. Conclusions BNT162b2 and mRNA-1273 were effective against COVID-19 following emergence of Omicron variant. A third dose provided additional protection over the primary series. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Research Review: Do antibullying interventions reduce internalizing symptoms? A systematic review, meta‐analysis, and meta‐regression exploring intervention components, moderators, and mechanisms

alexandrossfakianakis shared this article with you from Inoreader Research Review: Do antibullying interventions reduce internalizing symptoms? A systematic review, meta‐analysis, and meta‐regression exploring intervention components, moderators, and mechanisms Via Journal of Child Psychology and Psychiatry Background Effective antibullying interventions may reduce the impact of bullying on young people's mental health. Nevertheless, little is known about their effectiveness in reducing internalizing symptoms such as anxiety or depression, and what factors may influence intervention effects. The aim of this systematic review, meta-analysis, and metaregression is to assess the effects of school-based antibullying interventions on children's and adolescent's internalizing symptoms. The secondary aims are to explore potential moderators, intervention components, and reductions in bullying as mediators of intervention effects on internalizing symptoms. Methods We searched nine databases: PsycINFO, Web of Science, ERIC, SCOPUS, CINAHL, Medline, Embase, ProQuest, and Cochrane Library, and performed an author search of included studies in English from January 1983 to April 2021. We included studies that evaluated school-based antibullying interventions using controlled designs and reporting on both bullying and internalizing outcomes. Random-effects and metaregression models were used to derive Hedges g values with pooled 95% CIs as estimates of effect size and to test associations between moderator variables and effect size estimates. Path analysis was used to test potential mediation using effect size measures of victimization, perpetration, and internalizing outcomes. Quality and risk of bias were assessed using Cochrane collaboration tools. Results This review included 22 studies with 58,091 participants in the meta-analysis. Antibullying interventions had a very small effect in reducing overall internalizing symptoms (ES, 0.06; 95% CI, 0.0284 to 0.1005), anxiety (ES, 0.08; 95% CI, 0.011 to 0.158), and depression (ES, 0.06; 95% CI, 0.014 to 0.107) at postintervention. The reduction in internalizing symptoms did not vary significantly across geographic location, grade level, program duration, and intensity. The intervention component 'working with peers' was associated with a significant reduction, and 'using CBT techniques' was associated with a significant increase in internalizing outcomes. Bullying victimization and perpetration did not mediate the relationship between intervention condition and internalizing outcomes. Conclusions Antibullying interventions have a small impact on reducing internalizing symptoms. Ongoing development of antibullying interventions should address how best to maximize their impact on internalizing symptoms to safeguard young people from the damaging mental health outcomes of bullying. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Rab22a promotes the proliferation, migration, and invasion of lung adenocarcinoma via up-regulating PI3K/Akt/mTOR signaling pathway

alexandrossfakianakis shared this article with you from Inoreader Rab22a promotes the proliferation, migration, and invasion of lung adenocarcinoma via up-regulating PI3K/Akt/mTOR signaling pathway Via ScienceDirect Publication: Experimental Cell Research Publication date: Available online 27 April 2022 Source: Experimental Cell Research Author(s): Jinping Wang, Xue Luo, Jinxi Lu, Xi Wang, Yuan Miao, Qingchang Li, Liang Wang View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cytokine profile and cholesterol levels in patients with Niemann-Pick type C disease presenting neurological symptoms: The in vivo effect of miglustat and the in vitro effect of N-acetylcysteine and Coenzyme Q10

alexandrossfakianakis shared this article with you from Inoreader Cytokine profile and cholesterol levels in patients with Niemann-Pick type C disease presenting neurological symptoms: The <em>in vivo</em> effect of miglustat and the <em>in vitro</em> effect of N-acetylcysteine and Coenzyme Q10 Via ScienceDirect Publication: Experimental Cell Research Publication date: Available online 27 April 2022 Source: Experimental Cell Research Author(s): Tatiane G. Hammerschmidt, Bruna Donida, Jéssica L. Faverzani, Alana P. Moura, Bianca G. dos Reis, Andryele Z. Machado, Rejane G. Kessler, Fernanda M. Sebastião, Luiza S. Reinhardt, Dinara J. Moura, Carmen R. Vargas View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The intrinsic and microenvironmental features of diffuse midline glioma; implications for the development of effective immunotherapeutic treatment strategies

alexandrossfakianakis shared this article with you from Inoreader The intrinsic and microenvironmental features of diffuse midline glioma; implications for the development of effective immunotherapeutic treatment strategies Via Neuro-Oncology Advance Access Abstract Diffuse midline glioma (DMG), including those of the brainstem (diffuse intrinsic pontine glioma), are pediatric tumors of the central nervous system (CNS). Recognized as the most lethal of all childhood cancers, palliative radiotherapy remains the only proven treatment option, however, even for those that respond, survival is only temporarily extended. DMG harbor an immunologically 'cold' tumor microenvironment (TME) with few infiltrating immune cells. The mechanisms underpinning the cold TME are not well understood. Low expression levels of immune checkpoint proteins, including PD-1, PD-L1 and CTLA-4, are recurring features of DMG and likely contribute to the lack of response to immune checkpoint inhibitors (ICIs). The unique epigenetic signatures (including stem cell-like methylation patterns), a low tumor mutational burden, and recurring somatic mutations (H3K27M, TP53, ACVR1, MYC and PIK3CA), possibly play a role in the reduced efficacy of traditional immunotherapies. Therefore, to circumvent the lack of efficacy thus far seen for the use of ICIs, adoptive cell transfer (including chimeric antigen receptor T cells) and the use of oncolytic viruses, are currently being evaluated for the treatment of DMG. It remains an absolute imperative that we improve our understanding of DMG's intrinsic and TME features if patients are to realize the potential benefits offered by these sophisticated treatments. Herein, we summarize the limitations of immunotherapeutic approaches, highlight the emerging safety and clinical efficacy shown for sophisticated cell-based therapies, as well as the evolving knowledge underpinning the DMG-immune axis, to guide in the development of immunotherapies that we hope will improve outcomes. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Tetrahedral framework nucleic acid carrying angiogenic peptide prevents bisphosphonate-related osteonecrosis of the jaw by promoting angiogenesis

alexandrossfakianakis shared this article with you from Inoreader Tetrahedral framework nucleic acid carrying angiogenic peptide prevents bisphosphonate-related osteonecrosis of the jaw by promoting angiogenesis Via International Journal of Oral Science - Issue International Journal of Oral Science, Published online: 27 April 2022; doi:10.1038/s41368-022-00171-7 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.