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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Tracheostomy dependence following “organ preservation” (chemo)radiation protocol for laryngeal and hypopharyngeal cancers

alexandrossfakianakis shared this article with you from Inoreader Tracheostomy dependence following "organ preservation" (chemo)radiation protocol for laryngeal and hypopharyngeal cancers via Head & Neck Abstract Background Patients receiving primary (chemo)radiotherapy for laryngeal or hypopharyngeal cancer risk developing severe laryngeal dysfunction and becoming tracheostomy dependent, detracting from the benefits of organ preservation. We aim to describe the airway outcomes for this cohort and identify risk factors for developing tracheostomy dependence. Methods Patients with laryngeal or hypopharyngeal cancer who were recommended for and underwent primary (chemo)radiotherapy over a 6-year period were identified from a tertiary hospital Head and Neck cancer database. Patient, tumor, and treatment details were collected and analyzed. Results Of 166 patients, 18.7% (N = 31) required tracheostomy insertion. Advanced tumor classification was the only significant predictor (p < 0.00001). Successful decannulation was observed in 12.9% (N = 4). Decannulation was observably less successful with advanced tumors, bilateral vocal cord immobility, tracheostomies inserted under emergency conditions. Conclusion We quantified tracheostomy insertion rates and dependence in patients undergoing "organ-preserving" (chemo)radiotherapy, to assist in the pre-treatment counseling of patients opting for this approach. View on Web

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Opening a DOOR for pivotal studies: an example for complicated urinary tract infections

alexandrossfakianakis shared this article with you from Inoreader Opening a DOOR for pivotal studies: an example for complicated urinary tract infections via Clinical Infectious Diseases Advance Access 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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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 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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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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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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A Partial Ossicular Replacement Prosthesis With a Concentric Ball Joint in the Headplate

alexandrossfakianakis shared this article with you from Inoreader A Partial Ossicular Replacement Prosthesis With a Concentric Ball Joint in the Headplate via The Laryngoscope This study focuses on the development of the mCLIP ARC Partial Prosthesis, a new partial middle-ear prosthesis featuring a balanced, centered ball joint. The ball joint allows the headplate to adapt to the individual anatomical features of the reconstructed tympanic membrane and facilitates intraoperative handling. Objective In passive middle ear prosthetics, rigid implants have proven successful in reconstructing the ossicular chain. However, these cannot fully replicate the physiology of the ossicular chain. Pressure fluctuations cause high stresses in rigid passive prostheses, which can result in dislocation, protrusion, and pre-tension in the annular ligament resulting in unsatisfactory hearing results. Methods In collaboration with MED-EL, we developed a new passive middle ear prosthesis that features a balanced, centered ball joint between the headplate and shaft of the prosthesis. We compared the sound transmission properties of this new prosthesis with those of a standard rigid prosthesis. Using Laser-Doppler-Vibrometry, we measured the sound-induced velocity of the stapes footplate relative to a given acoustic stimulus. Results The new prosthesis showed equivalent sound transmission characteristics compared to the rigid prosthesis, whereas retaining the ability to compensate for pressure fluctuations due to its ball joint. This ensures good transmission properties even during displacements of the tympanic membrane. Conclusion This development is a further step toward a physiological reconstruction of the ossicular chain. Level of Evidence N/A Laryngoscope, 2022 View on Web

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