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

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Efficacy of Imaging Methods in the Detection and Diagnosis of Cerebrospinal Fluid Rhinorrhea

alexandrossfakianakis shared this article with you from Inoreader Efficacy of Imaging Methods in the Detection and Diagnosis of Cerebrospinal Fluid Rhinorrhea via The Laryngoscope We assess the diagnostic efficacy of various imaging methods in patients with suspected cerebrospinal fluid (CSF) rhinorrhea. This network meta-analysis demonstrates that intrathecal gadolinium-magnetic resonance cisternography is the most useful diagnostic method to detect CSF rhinorrhea. Objective To assess the diagnostic efficacy of various imaging methods in patients with suspected cerebrospinal fluid (CSF) rhinorrhea. Data Sources The PubMed, EMBASE, SCOPUS, Web of Science, Cochrane Trials, and Google Scholar databases were searched up to December 2021. Review Methods Diagnostic accuracy was compared among seven radiological methods: computed tomography (CT), CT cisternography (CTC), magnetic resonance imaging (MRI), magnetic resonance cisternography (MRC), CT + MRI, radionuclide cisternography, and intrathecal gadolinium (Gd)-MRC. Sensitivity, specificity, and accuracy were used as outcomes of the analysis. Both a traditional pairwise meta-analysis and a network meta-analysis were performed. Results Twenty-three trials were included in the analysis. The results of a network meta-analysis performed on a network consisting of seven diagnostic methods showed that all imaging modalities had greater diagnostic accuracy than CT, with the exception of CTC, which had lower sensitivity. Only intrathecal Gd-MRC was significantly superior to other imaging methods with regard to sensitivity and accuracy. Gd-MRC also showed the greatest surface under the cumulative ranking curve values for all of the outcomes (sensitivity: 0.9200; specificity: 0.8364; accuracy: 0.8920). Conclusion This network meta-analysis demonstrates that intrathecal Gd-MRC is the most useful diagnostic method to detect CSF rhinorrhea. Laryngoscope, 2022 View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.