CRISPR/Cas9‐HPV‐liposome enhances antitumor immunity and treatment of HPV infection associated cervical cancer

alexandrossfakianakis shared this article with you from Inoreader CRISPR/Cas9‐HPV‐liposome enhances antitumor immunity and treatment of HPV infection associated cervical cancer via Journal of Medical Virology ABSTRACT Increasing evidence shows that human papillomavirus (HPV) E6/E7 deletion in cervical cancer cells may be related to immunosuppressive tumour microenvironment and adverse reactions or resistance to immune checkpoint blockade. Here, we demonstrate that liposome delivery of CRISPR/cas9 can effectively knock out HPV, which in turn induces autophagy and triggers cell death-related immune activation by releasing damage-related molecular patterns. The results of in vivo experiments showed that HPV-targeting gRNA–liposomes could promote CD8+ T cell infiltration in tumour tissues; enhance the expression of pro-inflammatory cytokines, such as interleukin-12, tumour necrosis factor-α and interferon-γ and reduce regulatory T cells and myeloid suppressor cells. The combination of HPV-targeting gRNA–liposomes with immune checkpoint inhibitors and anti-programmed death-1 antibodies produced highly effective antitumour effects. In addition, combination therapy induced immune memory in the cervical cancer model. This article is protected by copyright. All rights reserved. View on Web

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Facial reactions to emotional films in young children with conduct problems and varying levels of callous‐unemotional traits

alexandrossfakianakis shared this article with you from Inoreader Facial reactions to emotional films in young children with conduct problems and varying levels of callous‐unemotional traits via Journal of Child Psychology and Psychiatry Background Elevated levels of callous-unemotional (CU) traits have proven useful for identifying a distinct subgroup of children whose conduct problems (CP) are early emerging, severe, persistent, and underpinned by aberrant emotional processing. The early childhood emotional experiences and expressions of CP subtypes are poorly understood, despite their importance to understanding the problematic attachments and atypical social affiliation experienced by children with elevated CU traits. The current study aimed to test for differences in facial emotional reactions to mood-inducing film clips in children with CP and varying levels of CU traits. Method We compared facial emotional reactions during a developmentally appropriate mood induction task in a mixed-sex sample of clinic-referred preschool children (M age = 3.64 years, SD = 0.63, 66.9% male) classified as CP with elevated levels of CU traits (CP + CU; n = 25) versus low CU traits (CP-only; n = 47), and typically developing children (TD; n = 28). Results Relative to TD children, children with clinical CP showed less congruent and more incongruent facial emotional expressions to sad and happy film clips, controlling for child sex, age, and ethnicity. Conclusions Consistent with older samples, young children with CP show atypical facial emotional expressions in response to positive and negative emotional stimuli. Findings have implications for developmental models of childhood antisocial behavior and can inform the development of targeted interventions. View on Web

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Transition Metals and Enterococcus faecalis: Homeostasis, Virulence and Perspectives

alexandrossfakianakis shared this article with you from Inoreader Transition Metals and Enterococcus faecalis: Homeostasis, Virulence and Perspectives via Molecular Oral Microbiology Abstract Enterococcus faecalis, a Gram-positive bacterium is known to be a key player in several chronic infections as well as nosocomial, heart valve, urinary tract, surgical wound and dental root canal infections. The capability to sense different transition metal levels and tune its response accordingly endows it with the potential to thrive and cause infections in several host niches. Over the past decade, our knowledge of how transition metals play a critical role in maintaining homeostasis of E. faecalis has improved significantly. The aim of this review is to elucidate the roles of metals such as iron, manganese, zinc and copper in the physiology, metabolism, and pathogenicity of E. faecalis. These essential micronutrients contribute to energy production, redox stress response, expression of virulence determinants, and cooperation in polymicrobial communities. The review also highlights metal homeostasis systems in E. faecalis, which respond to fluctuatio ns in extracellular metal levels, and regulate the intracellular metal content. Regulation of intracellular metallome secures the tolerance of E. faecalis to oxidative stress and host-mediated metal sequestration strategies. Therapeutic interventions which deprive E. faecalis of its essential metal requirements or disrupt its homeostatic control have been proposed to combat E. faecalis infections. This article is protected by copyright. All rights reserved View on Web

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The impact of extended treatment with artemether-lumefantrine on antimalarial exposure and reinfection risks in Ugandan children with uncomplicated malaria: A randomized controlled trial

alexandrossfakianakis shared this article with you from Inoreader The impact of extended treatment with artemether-lumefantrine on antimalarial exposure and reinfection risks in Ugandan children with uncomplicated malaria: A randomized controlled trial via Clinical Infectious Diseases Advance Access ABSTRACT Background. Artemether-lumefantrine (AL) is the most widely used artemisinin-based combination therapy (ACT) in sub-Saharan Africa and is threatened by the emergence of artemisinin resistance. Dosing is suboptimal in young children. We hypothesized that extending AL duration will improve exposure and reduce reinfection risks.Methods. We conducted a prospective, randomized, open-label pharmacokinetic/pharmacodynamic study of extended durat ion AL (EXALT) in children with malaria in high transmission rural Uganda. Children received 3-day (standard 6-dose) or 5-day (10-dose) AL with sampling for artemether, dihydroartemisinin (DHA), and lumefantrine over 42-day clinical follow-up. Primary outcomes were 1) comparative pharmacokinetic parameters between regimens, and 2) recurrent parasitemia analyzed as intention-to-treat.Results. 177 children ages 16 months to 16 years were randomized, contributing 227 total episodes. Terminal median lumefantrine concentrations were significantly increased in the 5-day versus 3-day regimen on days 7, 14, and 21 (p-values < 0.001). A pre-defined day 7 lumefantrine threshold of 280 ng/mL was strongly predictive of recurrence risk at 28 and 42 days (p < 0.001). Kaplan-Meier estimated 28-day (51% vs 40%) and 42-day risk (75% vs 68%) did not significantly differ between 3-day and 5-day regimens. No significant toxicity was seen with the extended regimen. Conclusions. Extending the duration of AL was safe and significantly enhanced overall drug exposure in young children but did not lead to significant reductions in recurrent parasitemia risk in our high transmission setting. However, day 7 levels were strongly predictive of recurrent parasitemia risk and those in the lowest weight-band were at higher risk of underdosing with the standard 3-day regimen. View on Web

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Molecular and regulatory mechanisms of oxidative stress adaptation in Streptococcus mutans

alexandrossfakianakis shared this article with you from Inoreader Molecular and regulatory mechanisms of oxidative stress adaptation in Streptococcus mutans via Molecular Oral Microbiology Abstract Dental caries is a chronic progressive disease, which destructs dental hard tissues under the influence of multiple factors, mainly bacteria. Streptococcus mutans (S. mutans) is the main cariogenic bacteria. However, its cariogenic virulence is affected by environmental stress such as oxidative stress, nutrient deficiency and low pH to some extent. Oxidative stress is one of the main stresses that S. mutans faces in oral cavity. But there are a variety of protective molecules to resist oxidative stress in S. mutans, including superoxide dismutase, nicotinamide adenine dinucleotide oxidase, Dps-like peroxide resistance protein, alkyl-hydrogen peroxide reductase, thioredoxin, glutamate-reducing protein system and some metabolic substances. Additionally, some transcriptional regulatory factors (SloR, PerR, Rex, Spx, etc.) and two-component systems are also closely related to oxidative stress adaptation by modulating the expression of protective molecules. This review summarizes the research progress of protective molecules and regulatory mechanisms (mainly transcription factors) of oxidative stress adaptation of S. mutans. This article is protected by copyright. All rights reserved View on Web

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Transfer effects from language processing to visual attention dynamics: The impact of orthographic transparency

alexandrossfakianakis shared this article with you from Inoreader Transfer effects from language processing to visual attention dynamics: The impact of orthographic transparency via British Journal of Psychology Abstract The consistency between letters and sounds varies across languages. These differences have been proposed to be associated with different reading mechanisms (lexical vs. phonological), processing grain sizes (coarse vs. fine) and attentional windows (whole words vs. individual letters). This study aimed to extend this idea to writing to dictation. For that purpose, we evaluated whether the use of different types of processing has a differential impact on local windowing attention: phonological (local) processing in a transparent language (Spanish) and lexical (global) processing of an opaque language (English). Spanish and English monolinguals (Experiment 1) and Spanish–English bilinguals (Experiment 2) performed a writing to dictation task followed by a global–local task. The first key performance showed a critical dissociation between languages: the response times (RTs) from the Spanish writing to dictation task was modulated by word length, whereas the RTs from the English w riting to dictation task was modulated by word frequency and age of acquisition, as evidence that language transparency biases processing towards phonological or lexical strategies. In addition, after a Spanish task, participants more efficiently processed local information, which resulted in both the benefit of global congruent information and the reduced cost of incongruent global information. Additionally, the results showed that bilinguals adapt their attentional processing depending on the orthographic transparency. View on Web

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The problem with picking: Permittance, escape and shame in problematic skin picking

alexandrossfakianakis shared this article with you from Inoreader The problem with picking: Permittance, escape and shame in problematic skin picking via Psychology and Psychotherapy: Theory, Research and Practice Abstract Objectives Problematic skin picking (SP) is a poorly understood experience characterised by a drive to pick the skin and related psychosocial impact. In the DSM-5, problematic SP is classified as 'excoriation (skin picking) disorder'. The aim of this article is to present a rare qualitative perspective on the lived experience of problematic SP, prioritising participants' voices and sense-making. Design An in-depth qualitative study of individuals who self-identified as picking their skin problematically and experienced related distress. Methods Seventeen UK-based participants were recruited online and interviewed about their SP. Participants were given choice of interview modality, including instant messenger platforms, telephone, email and Skype, to maximise comfort and improve the accessibility of the study. Transcripts were analysed using thematic analysis. Results Three themes offering novel insight into the phenomenology of participants' SP are highlighted and explored: (1) how cognitions and circumstances drove and permitted SP, (2) how participants 'zoned out' while SP and the escape or relief that this attentional experience offered and (3) participants' feelings of shame and distress in how they felt their SP may appear to others. Conclusions This study contributes in-depth and novel ideas to the understanding of SP phenomenology and identifies how environmental factors, cognitions, contextual distress and shame may be considerations in therapeutic intervention. It presents the complexity of SP sense-making and demonstrates the need for individual formulation. View on Web

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Use of Cold-Stored Whole Blood is Associated With Improved Mortality in Hemostatic Resuscitation of Major Bleeding: A Multicenter Study

alexandrossfakianakis shared this article with you from Inoreader Use of Cold-Stored Whole Blood is Associated With Improved Mortality in Hemostatic Resuscitation of Major Bleeding: A Multicenter Study via Annals of Surgery - Most Popular Articles Objective: The aim of this study was to identify a mortality benefit with the use of whole blood (WB) as part of the resuscitation of bleeding trauma patients. Background: Blood component therapy (BCT) is the current standard for resuscitating trauma patients, with WB emerging as the blood product of choice. We hypothesized that the use of WB versus BCT alone would result in decreased mortality. Methods: We performed a 14-center, prospective observational study of trauma patients who received WB versus BCT during their resuscitation. We applied a generalized linear mixed-effects model with a random effect and controlled for age, sex, mechanism of injury (MOI), and injury severity score. All patients who received blood as part of their initial resuscitation were included. Primary outcome was mortality and secondary outcomes included acute kidney injury, deep vein thrombosis/pulmonary embolism, pulmonary complications, and bleeding complications. Results: A total of 1623 [WB: 1180 (74%), BCT: 443(27%)] patients who sustained penetrating (53%) or blunt (47%) injury were included. Patients who received WB had a higher shock index (0.98 vs 0.83), more comorbidities, and more blunt MOI (all P View on Web

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Maxillary overdentures supported by four or six implants in the anterior region: 10‐year randomized controlled trial results

alexandrossfakianakis shared this article with you from Inoreader Maxillary overdentures supported by four or six implants in the anterior region: 10‐year randomized controlled trial results via Journal of Clinical Periodontology Abstract Objective To evaluate bar-supported maxillary implant overdenture treatment when supported by either four or six implants after 10 years. Material and methods Edentulous subjects with maxillary denture complaints and ample bone volume to facilitate implants in the anterior region of the maxilla were planned for implant-overdenture treatment, randomized to receive either four implants (n=25) or six implants (n=25) and subsequently evaluated after 10 years of function. Outcome variables included peri-implant bone level changes, implant and overdenture survival, complications, presence of plaque, calculus and bleeding, degree of peri-implant inflammation, probing depth and patient satisfaction. Differences between the groups and between evaluation periods were tested with a Student's t-test. Results Fourteen patients with totally 72 implants were lost to follow-up. Two patients from the 6-implant group experienced implant loss (four implants) resulting in 96.1 % implant survival in this group versus 100 % survival in the 4-implant group. Clinical, radiographical and patient-reported outcome measures did not differ statistical significantly between the two groups. Patients from both groups were generally quite satisfied with the result after 10 years. Conclusion Similar and favourable outcomes are seen in bar-supported maxillary overdentures on either four or six anteriorly placed implants after a 10-year evaluation period. This article is protected by copyright. All rights reserved. View on Web

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Tobacco smoke exacerbates Filifactor alocis pathogenicity

alexandrossfakianakis shared this article with you from Inoreader Tobacco smoke exacerbates Filifactor alocis pathogenicity via Journal of Clinical Periodontology Abstract Aims Filifactor alocis has recently emerged as a periodontal pathobiont that appears to thrive in the oral cavity of smokers. We hypothesized that identification of smoke-responsive F. alocis genes would provide insight into adaptive strategies and that cigarette smoke would enhance F. alocis pathogenesis in vivo. Materials and Methods F. alocis was grown in vitro and cigarette smoke extract-responsive genes determined by RNAseq. Mice were exposed, or not, to mainstream 1R6F research cigarette smoke and infected with F. alocis, or not, in an acute ligature model of periodontitis. Key clinical, infectious, and immune data were collected. Results In culture, F. alocis growth was unaffected by smoke conditioning and only a small number of genes were specifically regulated by smoke exposure. Reduced murine mass, differences in F. alocis-cognizant antibody production and altered immune profiles as well as altered alveolar bone loss were all attributable to smoke exposure and/or F. alocis infection in vivo. Conclusions F. alocis is well-adapted to tobacco-rich conditions and its pathogenesis is enhanced by tobacco smoke exposure. A smoke-exposed ligature model of periodontitis shows promise as a tool with which to further unravel mechanisms underlying tobacco-enhanced, bacteria-induced disease. View on Web

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