FKA‐A NPs enhances PTX‐A NPs efficacy to suppress ovarian cancer via regulating Skp2/YAP pathway

alexandrossfakianakis shared this article with you from Inoreader FKA‐A NPs enhances PTX‐A NPs efficacy to suppress ovarian cancer via regulating Skp2/YAP pathway via Fundamental & Clinical Pharmacology Abstract Recurrence and distant metastasis after paclitaxel (PTX)-based chemotherapy in ovarian cancer (OC) patients remains a clinical obstacle. Flavokawain A (FKA) is a novel chalcone from kava plant which can induce G2/M arrest and inhibit invasion and metastasis in different tumor cells. In this study, we examined the effects and the molecular mechanism of sodium aescinate (Aes)-stabilized nanoparticles FKA-A NPs in enhancing the efficacy of PTX-A NPs in vitro and in vivo. We showed that FKA-A NPs combined with PTX-A NPs notably inhibited the proliferation, migration and reduced the expression of EMT-related markers in OCs. YAP nuclear translocation and its downstream signaling pathway was remarkably activated after PTX-A NPs treatment in OCs. FKA-A NPs obviously inhibited YAP nuclear translocation and reduced the transcriptional activity of YAP target genes. Simultaneously, FKA-A NPs dose- and time-dependently inhibited Skp2 expression in A2780 and Skov3 cells. In contra st, overexpression of Skp2 significantly attenuated the inhibition of FKA-A NPs on YAP nuclear translocation. In OC homograft mice, treatment with FKA-A NPs and PTX-A NPs significantly suppressed the growth of homograft tumor compared with PTX-A NPs, but did not decrease mice's body weight. In summary, we demonstrate that FKA-A NPs enhance the efficacy of PTX-A NPs against OCs in vitro and in vivo via reducing Skp2 expression, thus suppressing YAP nuclear translocation and activity of its target genes. View on Web

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Curcumin reduces inflammation in rat apical periodontitis

alexandrossfakianakis shared this article with you from Inoreader Curcumin reduces inflammation in rat apical periodontitis via International Endodontic Journal Abstract Aim To evaluate the effect of systemic curcumin administration on the severity of apical periodontitis (AP). Methodology Forty male Wistar rats weighing 250-280g each, age 2.5 months, were distributed into four groups (n=10): control untreated rats (C), control rats treated with curcumin (CUR), rats with pulp exposure-induced apical periodontitis (AP), and rats with pulp exposure-induced apical periodontitis treated with curcumin (AP-CUR). Curcumin treatment was administered orally once daily for 15 days before pulp exposure and continued for 30 days after pulp exposure. The rats were sacrificed at 30 days, and the jaws were collected and reconstructed in a program specific for micro-CT. The jaws were processed for analysis of the inflammatory process using Haemotoxylin and Eosin staining and immunohistochemical assays for interleukin tumour necrosis factor alpha (TNF-α), interleukin (Il)-6, and Il-1β. Tartrate-resistant acid phosphatase (TRAP) and osteocalcin (OCN) staining were used to analyze the resorptive process on the bone surface of periapical area. Kruskal–Wallis with Dunn's test was performed for nonparametric data, and ANOVA with Tukey's test for parametric data, p < .05. Results Micro-CT revealed no statistically significant differences in bone resorption between the AP and AP-CUR groups (p > .05). The levels of inflammatory cell infiltration and immunoreactivity for the proinflammatory cytokines TNF-α, Il-6, and Il-1β were significantly higher in the periapical lesions of the AP group than in the AP-CUR group (p < .05). The number of TRAP-positive multinucleated cells was higher in the AP group than in the AP-CUR group (p < .05). In OCN-positive cells, no differences were observed between the AP and AP-CUR groups (p > .05). Conclusions Oral supplementation with curcumin had a significant effect on the AP severity in rats, suggesting an anti-inflammatory effect of curcumin on AP development. View on Web

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Infants Receiving Very Early ART Have High CD4 Counts in the First Year of Life

alexandrossfakianakis shared this article with you from Inoreader Infants Receiving Very Early ART Have High CD4 Counts in the First Year of Life via Clinical Infectious Diseases Advance Access ABSTRACT We followed 54 infants with in utero HIV after initiating very early antiretroviral treatment. At Weeks 24 and 48, ≥80% had CD4 ≥ 1500 cells/mm3 and CD4% ≥25%. Routine Pneumocystis jirovecii pneumonia prophylaxis in the first year of life may not be necessary for all very early treated infants. View on Web

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Monovalent rotavirus vaccine efficacy against different rotavirus genotypes: a pooled analysis of Phase II and III trial data

alexandrossfakianakis shared this article with you from Inoreader Monovalent rotavirus vaccine efficacy against different rotavirus genotypes: a pooled analysis of Phase II and III trial data via Clinical Infectious Diseases Advance Access Abstract Background Rotavirus vaccine performance appears worse in countries with high rotavirus genotype diversity. Evidence suggests diminished vaccine efficacy (VE) against G2P[4], which is heterotypic with existing monovalent rotavirus vaccine formulations. Most studies assessing genotype-specific VE have been underpowered and inconclusive. Methods We pooled individual-level data from ten Phase II and III clinical trials of rotavirus vaccine containing G1 and P[8] antigens (RV1) conducted between 2000 and 2012. We estimated VE against both any-severity and severe (Vesikari score ≥11) rotavirus gastroenteritis (RVGE) using binomial and multinomial logistic regression models for non-specific VE against any RVGE, genotype-specific VE, and RV1-typic VE against genotypes homotypic, partially heterotypic, or fully heterotypic with RV1 antigens. We adjusted models for concomitant oral poliovirus and RV1 vaccination and the country's de signated child mortality stratum. Results Analysis included 87,644 infants from 22 countries in the Americas, Europe, Africa, and Asia. For VE against severe RVGE, non-specific VE was 91% (95% confidence interval (CI): 87-94%). Genotype-specific VE ranged from 96% (95% CI: 89-98%) against G1P[8] to 71% (43-85%) against G2P[4]. RV1-typic VE was 92% (95% CI: 84-96%) against partially heterotypic genotypes but 83% (67-91%) against fully heterotypic genotypes. For VE against any-severity RVGE, non-specific VE was 82% (95% CI: 75-87%). Genotype-specific VE ranged from 94% (95% CI: 86-97%) against G1P[8] to 63% (41-77%) against G2P[4]. RV1-typic VE was 83% (95% CI: 72-90%) against partially heterotypic genotypes but 63% (40-77%) against fully heterotypic genotypes. Conclusions RV1 VE is comparatively diminished against fully heterotypic genotypes including G2P[4]. View on Web

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Effect of Repeat Vaccination on Immunogenicity of Quadrivalent Cell-Culture and Recombinant Influenza Vaccines Among Healthcare Personnel Aged 18-64 Years: A Randomized, Open-Label Trial

alexandrossfakianakis shared this article with you from Inoreader Effect of Repeat Vaccination on Immunogenicity of Quadrivalent Cell-Culture and Recombinant Influenza Vaccines Among Healthcare Personnel Aged 18-64 Years: A Randomized, Open-Label Trial via Clinical Infectious Diseases Advance Access Abstract Background Antibody responses to non-egg-based standard-dose cell-culture influenza vaccine (containing 15 µg hemagglutinin (HA)/component) and recombinant vaccine (containing 45 µg HA/component) during consecutive seasons have not been studied in the United States. Methods In a randomized trial of immunogenicity of quadrivalent influenza vaccines among healthcare personnel (HCP) aged 18–64 years over two consecutive seasons, HCP who received recombinant-hemagglutinin (RIV) or cell-culture-based vaccine (ccIIV) during the first season (Y1) were re-randomized the second season of 2019-2020 (Y2) to receive ccIIV or RIV, resulting in four ccIIV-RIV combinations. In Y2, hemagglutination inhibition (HI) antibody titers against reference cell-grown vaccine viruses were compared in each ccIIV-RIV group with titers among HCP randomized both seasons to receive egg-based, standard-dose inactivated influenza vaccine (IIV), using geome tric mean titer (GMT) ratios of Y2-post-vaccination titers. Results Y2 data from 414 HCPs were analyzed per-protocol. Compared to 60 IIV/IIV recipients, 74 RIV/RIV and 106 ccIIV/RIV recipients showed significantly elevated GMT ratios (Bonferroni corrected P <.007) against all components except A (H3N2). Post-vaccination GMT ratios for ccIIV/ccIIV and RIV/ccIIV were not significantly elevated compared to IIV/IIV except for RIV/ccIIV against A(H1N1)pdm09. Conclusions In adult HCPs, receipt of RIV two consecutive seasons or the second season was more immunogenic than consecutive egg-based IIV for three of the four components of quadrivalent vaccine. Immunogenicity of ccIIV/ccIIV was similar to that of IIV/IIV. Differences in hemagglutinin antigen content may play a role in immunogenicity of influenza vaccination in consecutive seasons. View on Web

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Coinfections in hospitalized patients with severe fever with thrombocytopenia syndrome: a retrospective study

alexandrossfakianakis shared this article with you from Inoreader Coinfections in hospitalized patients with severe fever with thrombocytopenia syndrome: a retrospective study via Journal of Medical Virology Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high case fatality rate. Few studies have been performed on bacterial or fungal coinfections or the effect of antibiotics therapy. Study design A retrospective, observational study was performed to assess the prevalence of bacterial and fungal coinfections in patients hospitalized for SFTSV infection. The most commonly involved microorganisms and the effect of antimicrobial therapy were determined by the site and source of infection. Results A total of 1201 patients hospitalized with SFTSV infection were included; 359 (29.9%) had microbiologically confirmed infections, comprised of 292 with community-acquired infections (CAIs) and 67 with healthcare-associated infections (HAIs). Death was independently associated with HAIs, with a more significant effect than that observed for CAIs. For bacterial infections, only those acquired in hospital were associated with fatal outcomes, while fungal infection, whether acquired in hospital or community, was related to an increased risk of fatal outcomes. The infections in respiratory tract and bloodstream were associated with a higher risk of death than that in urinary tract. Both antibiotic and antifungal treatments were associated with improved survival for CAIs, while for HAIs, only antibiotic therapy was related to improved survival, and no effect from antifungal therapy was observed. Early administration of glucocorticoids was associated with an increased risk of HAIs. Conclusion The study provided novel clinical and epidemiological data and revealed risk factors, such as bacterial coinfections, fungal coinfections, infection sources, and treatment strategies associated with SFTS deaths/survival. This report might be helpful in curing SFTS and reducing fatal SFTS. This article is protected by copyright. All rights reserved. View on Web

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The emergence, spread and vanishing of a French SARS‐CoV‐2 variant exemplifies the fate of RNA virus epidemics and obeys the Mistigri rule

alexandrossfakianakis shared this article with you from Inoreader The emergence, spread and vanishing of a French SARS‐CoV‐2 variant exemplifies the fate of RNA virus epidemics and obeys the Mistigri rule via Journal of Medical Virology Abstract The nature and dynamics of mutations associated with the emergence, spread and vanishing of SARS-CoV-2 variants causing successive waves are complex. We determined the kinetics of the most common French variant ("Marseille-4") for 10 months since its onset in July 2020. Here, we analysed and classified into subvariants and lineages 7,453 genomes obtained by next-generation sequencing. We identified two subvariants, Marseille-4A, which contains 22 different lineages of at least 50 genomes, and Marseille-4B. Their average lifetime was 4.1±1.4 months, during which 4.1±2.6 mutations accumulated. Growth rate was 0.079±0.045, varying from 0.010 to 0.173. Most of the lineages exhibited a bell-shaped distribution. Several beneficial mutations at unpredicted sites initiated a new outbreak, while the accumulation of other mutations resulted in more viral heterogenicity, increased diversity and vanishing of the lineages. Marseille-4B emerged when the other Marse ille-4 lineages vanished. Its ORF8 gene was knocked out by a stop codon, as reported in SARS-CoV-2 of mink and in the Alpha variant. This subvariant was associated with increased hospitalization and death rates, suggesting that ORF8 is a nonvirulence gene. We speculate that the observed heterogenicity of a lineage may predict the end of the outbreak. This article is protected by copyright. All rights reserved. View on Web

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Radiological anatomical variations of the lateral nasal wall and anterior skull base amongst different populations: A systematic review and meta‐analysis

alexandrossfakianakis shared this article with you from Inoreader Radiological anatomical variations of the lateral nasal wall and anterior skull base amongst different populations: A systematic review and meta‐analysis via Clinical Otolaryngology Abstract Objectives To determine the anatomical variations of the lateral nasal wall and anterior skull base amongst populations in different geographical regions. Design Systematic review and meta-analysis. Methods Using PRISMA guidelines, SCOPUS and PUBMED databases were searched from inception until 1st March 2022. The regions and populations identified were from Europe, Asia, Middle East, Australia-New Zealand-Oceania, South America, North America and Africa. Random-effects model was used to estimate the pooled prevalence with 95% confidence intervals (CIs). Heterogeneity was assessed using the I 2 statistic and Cochran's Q test. Main outcome measures Anatomical variations of the lateral nasal wall and anterior skull base confirmed by computed tomography scan. Results 56 articles were included with a total of 11805 persons. The most common anatomical variation of the ostiomeatal complex was pneumatization of the agger nasi (84.1%), olfactory fossa was Keros type 2 (53.8%) and ethmoids was asymmetry of the roof (42.8%). Sphenoethmoidal and suprabullar cells have a higher prevalence in North Americans (53.7%, 95% CI: 46.00-61.33) while asymmetry of ethmoid roof more common in Middle Easterns (85.5%, 95% CI: 0.00-100). Bent uncinate process has greater prevalence in Asians while supraorbital ethmoid cells and Keros type 3 more common in non-Asians. The overall studies have substantial heterogeneity and publication bias. Conclusions Certain anatomic variants are more common in a specific population. The 'approach of analysis' plays a role in the prevalence estimates and consensus should be made in future studies regarding the most appropriate 'approach of analysis' either by persons or by sides. View on Web

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Epidemiology and Etiology of Chronic Rhinosinusitis in Asia – a Narrative Review

alexandrossfakianakis shared this article with you from Inoreader Epidemiology and Etiology of Chronic Rhinosinusitis in Asia – a Narrative Review via Clinical Otolaryngology Abstract Background Despite having a similar prevalence to Western populations, literature on chronic rhinosinusitis (CRS) in the Asian population is sparse. There is limited data on the epidemiology and etiology of CRS in Asia. Objectives To review the current literature on the epidemiology and etiology of chronic rhinosinusitis (CRS) in Asia. Methods This is a narrative review of published data on the epidemiology and etiology of CRS. Studies on CRS in Asian countries, published in English and indexed on PubMed or Google Scholar were reviewed. Where available, data extracted included epidemiology, endotype and cytokine profiles and genetic profiles. Results and Conclusion The prevalence of CRS in Asia ranges widely from 2.1% -28.4%. Type 2 inflammation has been reported in 5-55% of Asian patients, with lower levels of Type 2 cytokines reported in head to head comparisons of Western vs Asian patients. Notably, there exists marked heterogeneity in criterion of the tissue eosinophilic infiltration for diagnosis of type 2 chronic rhinosinusitis. Our review suggests that differences in prevalence of CRS and proportion of eosinophilic CRS between Asia and Europe and the Americas requires further study. Large-scale Asian studies utilizing standardized definitions are needed to bridge this gap. Head to head genetic and microbiomal analysis may also be useful in understanding differences in CRS between the Asian and Western populations. View on Web

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The analgesic and anti‐hemorrhagic efficacy of platelet‐rich plasma in tonsillectomy: A systematic review and meta‐analysis of randomized controlled trials

alexandrossfakianakis shared this article with you from Inoreader The analgesic and anti‐hemorrhagic efficacy of platelet‐rich plasma in tonsillectomy: A systematic review and meta‐analysis of randomized controlled trials via Clinical Otolaryngology Abstract Aim To conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) that evaluated the analgesic and anti-hemorrhagic efficacy of platelet-rich plasma (PRP) among patients undergoing tonsillectomy. Methods PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases were screened from inception until July 2021, and updated in December 2021. Risk of bias of the included studies was evaluated according to the Cochrane Collaboration tool. The efficacy endpoints were summarized as risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI). Results Seven RCTs were analyzed, comprising a total of 392 patients. Risk of bias evaluation showed an overall high risk in one RCT, low risk in four RCTs, and some concerns in two RCTs. The pooled results revealed that the mean postoperative pain score was significantly reduced in favor of the PRP group compared with the control group (SMD=-1.38, 95% CI [-1.91, -0.85], p<0.001). Subgroup analysis showed the effect estimate was statistically significant for early postoperative pain (day 0 to day 3), without substantial difference between both groups on late postoperative pain (day 5 and day 7). Moreover, the rate of postoperative hemorrhage was significantly reduced in favor of the PRP group compared with the control group (RR=0.16, 95% CI [0.05, 0.50], p=0.001). Subgroup analysis showed the effect estimate was statistically significant for the rate of primary and secondary hemorrhage. Conclusion PRP was associated with significant reduction in postoperative pain and hemorrhage among patients undergoing tonsillectomy. This article is protected by copyright. All rights reserved. View on Web

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