bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterisation of plasmodial transketolases and identification of potential inhibitors: an in silico study
Authors: Boateng Rita Afriyie , Tastan Bishop Özlem , Musyoka Thommas Mutemi
Published: November 2020

Background

Plasmodial transketolase (PTKT) enzyme is one of the novel pharmacological targets being explored as potential anti-malarial drug target due to its functional role and low sequence identity to the human enzyme. Despite this, features contributing to such have not been exploited for anti-malarial drug design. Additionally, there are no anti-malarial drugs targeting PTKTs whereas the broad activity of these inhibitors against PTKTs from otherPlasmodiumspp. is yet to be reported. This study characterises different PTKTs [Plasmodium falciparum(PfTKT),Plasmodium vivax(PvTKT),Plasmodium ovale(PoTKT),Plasmodium malariae(PmTKT) andPlasmodium knowlesi(PkTKT) and the human homolog (HsTKT)] to identify key sequence and structural based differences as well as the identification of selective potential inhibitors against PTKTs.

Methods

A sequence-based study was carried out using multiple sequence alignment, phylogenetic tree calculations and motif discovery analysis. Additionally, TKT models ofPfTKT,PmTKT,PoTKT,PmTKT andPkTKT were modelled using theSaccharomyces cerevisiaeTKT structure as template. Based on the modelled structures, molecular docking using 623 South African natural compounds was done. The stability, conformational changes and detailed interactions of selected compounds were accessed viz all-atom molecular dynamics (MD) simulations and binding free energy (BFE) calculations.

Results

Sequence alignment, evolutionary and motif analyses revealed key differences between plasmodial and the human TKTs. High quality homodimeric three-dimensional PTKTs structures were constructed. Molecular docking results identified three compounds (SANC00107, SANC00411 and SANC00620) which selectively bind in the active site of all PTKTs with the lowest (better) binding affinity ≤ − 8.5 kcal/mol. MD simulations of ligand-bound systems showed stable fluctuations upon ligand binding. In all systems, ligands bind stably throughout the simulation and form crucial interactions with key active site residues. Simulations of selected compounds in complex with human TKT showed that ligands exited their binding sites at different time steps. BFE of protein–ligand complexes showed key residues involved in binding.

Conclusions

This study highlights significant differences between plasmodial and human TKTs and may provide valuable information for the development of novel anti-malarial inhibitors. Identified compounds may provide a starting point in the rational design of PTKT inhibitors and analogues based on these scaffolds.
Clinical syndromes and treatment location predict utility of carbapenem sparing therapies in ceftriaxone-non-susceptible Escherichia coli bloodstream infection
Authors: Xie Ouli , Cisera Kathryn , Taylor Lucy , Hughes Carly , Rogers Benjamin
Published: November 2020

Background

Cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, intravenous fosfomycin and plazomicin represent potential carbapenem sparing agents for extended-spectrum-beta-lactamase or AmpC beta-lactamase producing Escherichia coli infection. However, available data is limited in predicting the volume of carbapenem therapy which could be substituted and real-world contraindications.

Methods

We determined the number of carbapenem days of therapy (DOT) which could be substituted and frequent contraindications accounting for antimicrobial susceptibility and site of infection in an unselected cohort with ceftriaxone-non-susceptible E. coli bacteremia at a single health network from 2015 to 2016. Individual patient data was used to calculate DOT and substitution for each agent.

Results

There were 108 episodes of E. coli bacteremia resulting in 67.2 carbapenem DOT/100 patient-days of antimicrobial therapy administered. Ceftazidime-avibactam could be used to substitute 36.2 DOT/100 patient-days (54%) for inpatient definitive therapy, ceftolozane-tazobactam for 34.7 DOT/100 patient-days (52%), cefiderocol for 27.1 DOT/100 patient-days (40%), fosfomycin for 23.3 DOT /100 patient-days (35%) and plazomicin for 27.1 DOT/100 patient-days (40%). Non-urinary tract source of infection was the most frequent contraindication to fosfomycin (25), plazomicin (26) and cefiderocol (26). Use in outpatient parenteral antimicrobial therapy (OPAT) programs accounted for 40% of DOT, all of which could be substituted if stability data allowed for ceftazidime-avibactam and ceftolozane-tazobactam.

Conclusions

All tested agents could be used to replace a significant volume of carbapenem therapy. Establishing stability of these agents for use in OPAT is required for maximizing their use as carbapenem sparing agents while randomized clinical data is awaited for some of these agents in resistant E. coli bacteremia.
Retraction Note: Glycol chitosan incorporated retinoic acid chlorochalcone (RACC) nanoparticles in the treatment of Osteosarcoma
Authors: Qin Yan-Guo , Zhu Lan-Yu , Wang Chen-Yu , Zhang Bo-Yan , Wang Qing-Yu , Li Rui-Yan , Liu Zhen
Published: November 2020

This article has been retracted. Please see the Retraction Notice for more detail: 10.1186/s12944-020-01416-2
Perceived changes of specific attitudes, perceptions and behaviors during the Corona pandemic and their relation to wellbeing
Authors: Büssing Arndt , Rodrigues Recchia Daniela , Hein Rudolf , Dienberg Thomas
Published: November 2020

Background

During the COVID-19 pandemic, most people had to cope with the restrictions of the lockdown, leaving them to their fears, insecurity and isolation. On the other hand, due to the unexpected ‘extra time’ there was room for new experiences and for personal reflections on what is essential in life, to perceive nature and relations more consciously etc. We, therefore, intended to analyze perceived changes of attitudes and behaviors during the time of lockdown, and whether these perceptions would contribute to personal wellbeing during the pandemic.

Methods

An anonym cross-sectional online survey was performed for data collection, using standardized questionnaires, i.e., the WHO-Five Well-being Index (WHO-5), Brief Multidimensional Life Satisfaction Scale (BMLSS), Awe/Gratitude scale (GrAw-7), and the newly developed Perceived Changes Questionnaire (PCQ).

Results

Within the number of respondents (n = 1277), women were predominating (67.5%). Participants’ mean age was 50.9 ± 14.9 years. Exploratory factor analyses showed that the 24-item Perceived Changes Questionnaire differentiated five factors that would account for 61% of variance: (1) Nature/Silence/Contemplation (Cronbach’s alpha = .87), (2) Spirituality (Cronbach’s alpha = .83), (3) Relationships (Cronbach’s alpha = .80), (4) Reflection on life (Cronbach’s alpha = .74), (5) Digital media usage (Cronbach’s alpha = .74). Strongest changes were observed for Relationships and Nature/Silence/Contemplation. Perceived changes were stronger among older persons, among persons with higher wellbeing, and among those who relied on their faith as a resource. These changes were predicted best by a person’s perception of wondering awe in distinct situations with subsequent feelings of gratitude. Stepwise regression analyzes revealed that participants’ wellbeing was explained best by low perceived burden and high life satisfaction (R2 = .46). Awe/gratitude, perceived changes in terms of Nature/Silence/Contemplation and low Reflections of live are further variables that would predict a person’s wellbeing among the COVID-19 pandemic.

Conclusions

During the Corona pandemic, people tried to find ways to adapt to the outcomes of the restrictions. The perceived changes of attitudes and behaviors can be interpreted in terms of a reappraisal strategy. These can be measured with the extended version of the PCQ which was found to have good quality indices and a plausible factor structure. The reported changes contribute to persons’ wellbeing only to some extend, indicating that they represent an independent quality of relevance in peoples’ life.
Increasing the information provided by probabilistic sensitivity analysis: The relative density plot
Authors: Geenen Joost W. , Vreman Rick A. , Boersma Cornelis , Klungel Olaf H. , Hövels Anke M. , Ham Renske M. T. Ten
Published: November 2020

Background

Results of probabilistic sensitivity analyses (PSA) are frequently visualized as a scatterplot, which is limited through overdrawing and a lack of insight in relative density. To overcome these limitations, we have developed the Relative Density plot (PSA-ReD).

Methods

The PSA-ReD combines a density plot and a contour plot to visualize and quantify PSA results. Relative density, depicted using a color gradient, is transformed to a cumulative probability. Contours are then plotted over regions with a specific cumulative probability. We use two real-world case studies to demonstrate the value of the PSA-ReD plot.

Results

The PSA-ReD method demonstrates proof-of-concept and feasibility. In the real-world case-studies, PSA-ReD provided additional visual information that could not be understood from the traditional scatterplot. High density areas were identified by color-coding and the contour plot allowed for quantification of PSA iterations within areas of the cost-effectiveness plane, diminishing overdrawing and putting infrequent iterations in perspective. Critically, the PSA-ReD plot informs modellers about non-linearities within their model.

Conclusions

The PSA-ReD plot is easy to implement, presents more of the information enclosed in PSA data, and prevents inappropriate interpretation of PSA results. It gives modelers additional insight in model functioning and the distribution of uncertainty around the cost-effectiveness estimate.
Right ventricular-arterial uncoupling independently predicts survival in COVID-19 ARDS
Authors: D’Alto Michele , Marra Alberto M. , Severino Sergio , Salzano Andrea , Romeo Emanuele , De Rosa Rosanna , Stagnaro Francesca Maria , Pagnano Gianpiero , Verde Raffaele , Murino Patrizia , Farro Andrea , Ciccarelli Giovanni , Vargas Maria , Fiorentino Giuseppe , Servillo Giuseppe , Gentile Ivan , Corcione Antonio , Cittadini Antonio , Naeije Robert , Golino Paolo
Published: November 2020

Aim

To investigate the prevalence and prognostic impact of right heart failure and right ventricular-arterial uncoupling in Corona Virus Infectious Disease 2019 (COVID-19) complicated by an Acute Respiratory Distress Syndrome (ARDS).

Methods

Ninety-four consecutive patients (mean age 64 years) admitted for acute respiratory failure on COVID-19 were enrolled. Coupling of right ventricular function to the pulmonary circulation was evaluated by a comprehensive trans-thoracic echocardiography with focus on the tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (PASP) ratio

Results

The majority of patients needed ventilatory support, which was noninvasive in 22 and invasive in 37. There were 25 deaths, all in the invasively ventilated patients. Survivors were younger (62 ± 13 vs. 68 ± 12 years, p = 0.033), less often overweight or usual smokers, had lower NT-proBNP and interleukin-6, and higher arterial partial pressure of oxygen (PaO2)/fraction of inspired O2 (FIO2) ratio (270 ± 104 vs. 117 ± 57 mmHg, p < 0.001). In the non-survivors, PASP was increased (42 ± 12 vs. 30 ± 7 mmHg, p < 0.001), while TAPSE was decreased (19 ± 4 vs. 25 ± 4 mm, p < 0.001). Accordingly, the TAPSE/PASP ratio was lower than in the survivors (0.51 ± 0.22 vs. 0.89 ± 0.29 mm/mmHg, p < 0.001). At univariate/multivariable analysis, the TAPSE/PASP (HR: 0.026; 95%CI 0.01–0.579; p: 0.019) and PaO2/FIO2 (HR: 0.988; 95%CI 0.988–0.998; p: 0.018) ratios were the only independent predictors of mortality, with ROC-determined cutoff values of 159 mmHg and 0.635 mm/mmHg, respectively.

Conclusions

COVID-19 ARDS is associated with clinically relevant uncoupling of right ventricular function from the pulmonary circulation; bedside echocardiography of TAPSE/PASP adds to the prognostic relevance of PaO2/FIO2 in ARDS on COVID-19.
Engineering prokaryotic regulator IrrE to enhance stress tolerance in budding yeast
Authors: Wang Li , Wang Xin , He Zhi-Qiang , Zhou Si-Jie , Xu Li , Tan Xiao-Yu , Xu Tao , Li Bing-Zhi , Yuan Ying-Jin
Published: November 2020

Background

Stress tolerance is one of the important desired microbial traits for industrial bioprocesses, and global regulatory protein engineering is an efficient approach to improve strain tolerance. In our study, IrrE, a global regulatory protein from the prokaryotic organismDeinococcus radiodurans, was engineered to confer yeast improved tolerance to the inhibitors in lignocellulose hydrolysates or high temperatures.

Results

Three IrrE mutations were developed through directed evolution, and the expression of these mutants could improve the yeast fermentation rate by threefold or more in the presence of multiple inhibitors. Subsequently, the tolerance to multiple inhibitors of single-site mutants based on the mutations from the variants were then evaluated, and 11 mutants, including L65P, I103T, E119V, L160F, P162S, M169V, V204A, R244G, Base 824 Deletion, V299A, and A300V were identified to be critical for the improved representative inhibitors, i.e., furfural, acetic acid and phenol (FAP) tolerance. Further studies indicated that IrrE caused genome-wide transcriptional perturbation in yeast, and the mutant I24 led to the rapid growth ofSaccharomyces cerevisiaeby primarily regulating the transcription level of transcription activators/factors, protecting the intracellular environment and enhancing the antioxidant capacity under inhibitor environments, which reflected IrrE plasticity. Meanwhile, we observed that the expression of the wild-type or mutant IrrE could also protectSaccharomyces cerevisiaefrom the damage caused by thermal stress. The recombinant yeast strains were able to grow with glucose at 42 ℃.

Conclusions

IrrE fromDeinococcus radioduranscan be engineered as a tolerance-enhancer forSaccharomyces cerevisiae. Systematic research on the regulatory model and mechanism of a prokaryotic global regulatory factor IrrE to increase yeast tolerance provided valuable insights for the improvements in microbial tolerance to complex industrial stress conditions.
Investigation of the piroplasm diversity circulating in wildlife and cattle of the greater Kafue ecosystem, Zambia
Authors: Squarre David , Nakamura Yukiko , Hayashida Kyoko , Kawai Naoko , Chambaro Herman , Namangala Boniface , Sugimoto Chihiro , Yamagishi Junya
Published: November 2020

Background

Piroplasms are vector-borne intracellular hemoprotozoan parasites that infect wildlife and livestock. Wildlife species are reservoir hosts to a diversity of piroplasms and play an important role in the circulation, maintenance and evolution of these parasites. The potential for likely spillover of both pathogenic and non-pathogenic piroplasm parasites from wildlife to livestock is underlined when a common ecological niche is shared in the presence of a competent vector.

Method

To investigate piroplasm diversity in wildlife and the cattle population of the greater Kafue ecosystem, we utilized PCR to amplify the 18S rRNA V4 hyper-variable region and meta-barcoding strategy using the Illumina MiSeq sequencing platform and amplicon sequence variant (ASV)-based bioinformatics pipeline to generate high-resolution data that discriminate sequences down to a single nucleotide difference.

Results

A parasite community of 45 ASVs corresponding to 23 species consisting of 4 genera of Babesia, Theileria, Hepatozoon and Colpodella, were identified in wildlife and the cattle population from the study area. Theileria species were detected in buffalo, impala, hartebeest, sable antelope, sitatunga, wild dog and cattle. In contrast, Babesia species were only observed in cattle and wild dog. Our results demonstrate possible spillover of these hemoprotozoan parasites from wildlife, especially buffalo, to the cattle population in the wildlife-livestock interface.

Conclusion

We demonstrated that the deep amplicon sequencing of the 18S rRNA V4 hyper-variable region for wildlife was informative. Our results illustrated the diversity of piroplasma and the specificity of their hosts. They led us to speculate a possible ecological cycle including transmission from wildlife to domestic animals in the greater Kafue ecosystem. Thus, this approach may contribute to the establishment of appropriate disease control strategies in wildlife-livestock interface areas.

Graphical Abstract
Parkinson’s disease and translational research
Authors: Dinter Elisabeth , Saridaki Theodora , Diederichs Leonie , Reichmann Heinz , Falkenburger Björn H.
Published: November 2020

Parkinson’s disease (PD) is diagnosed when patients exhibit bradykinesia with tremor and/or rigidity, and when these symptoms respond to dopaminergic medications. Yet in the last years there was a greater recognition of additional aspects of the disease including non-motor symptoms and prodromal states with associated pathology in various regions of the nervous system. In this review we discuss current concepts of two major alterations found during the course of the disease: cytoplasmic aggregates of the protein α-synuclein and the degeneration of dopaminergic neurons. We provide an overview of new approaches in this field based on current concepts and latest literature. In many areas, translational research on PD has advanced the understanding of the disease but there is still a need for more effective therapeutic options based on the insights into the basic biological phenomena.
Recommendations for the use of long-term experience sampling in bipolar disorder care: a qualitative study of patient and clinician experiences
Authors: Bos Fionneke M. , Snippe Evelien , Bruggeman Richard , Doornbos Bennard , Wichers Marieke , van der Krieke Lian
Published: November 2020

Background

Self-monitoring has been shown to improve the self-management and treatment of patients with bipolar disorder. However, current self-monitoring methods are limited to once-daily retrospectively assessed mood, which may not suit the rapid mood fluctuations in bipolar disorder. The experience sampling method (ESM), which assesses mood in real-time several times a day, may overcome these limitations. This study set out to assess the experiences of patients and clinicians with the addition of ESM monitoring, real-time alerts, and personalized feedback to clinical care. Participants were twenty patients with bipolar disorder type I/II and their clinicians. For four months, patients completed five ESM assessments per day on mood, symptoms, and activities. Weekly symptom questionnaires alerted patients and clinicians to potential episodes. After the monitoring, a personalized feedback report based on the patient’s data was discussed between patient and clinician. Three months later, patient and clinician were both interviewed.

Results

Thematic analysis of the transcripts resulted in four themes: perceived effects of the monitoring, alerts, and feedback, and recommendations for implementation of ESM. ESM was perceived as helping patients to cope better with their disorder by increasing awareness, offering new insights, and encouraging life style adjustments. ESM was further believed to facilitate communication between patient and clinician and to lead to new treatment directions. However, high assessment burden and pre-occupation with negative mood and having a disorder were also described. Patients and clinicians advocated for increased personalization and embedding of ESM in care.

Conclusions

This study demonstrates that long-term ESM monitoring, alerts, and personalized feedback are perceived as beneficial to the treatment and self-management of patients with bipolar disorder. Future research should further test the clinical utility of ESM. Clinically relevant feedback and technology need to be developed to enable personalized integration of ESM in clinical care.
Immobilization of molecular catalysts for artificial photosynthesis
Authors: Whang Dong Ryeol
Published: November 2020

Artificial photosynthesis offers a way of producing fuels or high-value chemicals using a limitless energy source of sunlight and abundant resources such as water, CO2, and/or O2. Inspired by the strategies in natural photosynthesis, researchers have developed a number of homogeneous molecular systems for photocatalytic, photoelectrocatalytic, and electrocatalytic artificial photosynthesis. However, their photochemical instability in homogeneous solution are hurdles for scaled application in real life. Immobilization of molecular catalysts in solid supports support provides a fine blueprint to tackle this issue. This review highlights the recent developments in (i) techniques for immobilizing molecular catalysts in solid supports and (ii) catalytic water splitting, CO2 reduction, and O2 reduction with the support-immobilized molecular catalysts. Remaining challenges for molecular catalyst-based devices for artificial photosynthesis are discussed in the end of this review.
Robotic-assisted Unicompartmental knee Arthroplasty optimizes joint line restitution better than conventional surgery
Authors: Negrín Roberto , Duboy Jaime , Reyes Nicolás O. , Barahona Maximiliano , Iñiguez Magaly , Infante Carlos , Cordero José Antonio , Sepulveda Vicente , Ferrer Gonzalo
Published: November 2020

Purpose

To compare joint line restoration after unicompartmental knee arthroplasty (UKA) between conventional and robotic-assisted surgery. Previous studies have shown that joint line distalization can lead to higher failure rates. The hypothesis was that robotic-assisted UKA is associated with less femoral component distalization and a precise tibial cut, which allows a more anatomical restitution of the knee joint line.

Methods

Retrospective cohort study of patients undergoing medial or lateral UKA between May 2018 and March 2020. Preoperative and postoperative radiologic assessment of the joint line was performed by two observers, using three different methods, one for tibial slope and one for tibial resection. Robotic assisted UKA and conventional UKA groups were compared.

Results

Sixty UKA were included, of which 48 (77.42%) were medial. Robotic-assisted UKA were 40 (64.52%) and 22(35.48%) were conventional

The distalization of the femoral component was higher in the conventional group despite the method of measurement used In both Weber methods, the difference was statistically different: Conventional 2.3 (0.9 to 5.6) v/s Robotic 1.5 (− 1.1 to 4.1) (p =0.0025*). A higher proportion of patients achieved a femoral component position ≤ two millimeters from the joint line using robotic-assisted UKA compared to the conventional technique .

No statistical difference between robotic-assisted and conventional UKA was found in tibial resection and slope.

Conclusion

Robotic-assisted UKA shows a better rate of joint line restoration due to less femoral component distalization than conventional UKA. No difference was found in the amount of tibial resection between groups in this study.

Level of evidence

III
Mothers’ knowledge and attitudes regarding child feeding recommendations, complementary feeding practices and determinants of adequate diet
Authors: Bimpong Kingsley Appiah , Cheyuo Ernest Kaa-Emabong , Abdul-Mumin Alhassan , Ayanore Martin A. , Kubuga Clement K. , Mogre Victor
Published: November 2020

Background

Complementary feeding is critical for optimal nutrition in infants and young children as it ensures their growth, health and development to attain their full potential. However, evidence shows that children from developing countries do not meet the core indicators for appropriate complementary feeding. We evaluated mothers’ knowledge and attitudes regarding child feeding recommendations and the determinants of adequate diet among children aged 6–23 months.

Methods

This cross-sectional study included 200 children aged 6–23 months and their mothers/care givers recruited during child welfare clinics of two health facilities in Ghana. Data was collected using a structured questionnaire. Multivariate logistic regression was used to assess determinants of adequate diet.

Results

Sixty-eight percent of the mothers knew the recommended duration of continued breastfeeding, 56.5% how to ensure dietary diversity and enrich their children’s diets and 94% (n = 188) had positive attitude towards recommended infant and young child feeding practices. Majority of the mothers (92%, n = 183) practiced continued breastfeeding, 10.5% of the children met minimum diet diversity score, 39.5% minimum meal frequency and 8.5% received minimum adequate diet. Determinants of receipt of minimum adequate diet were: having high knowledge in child feeding recommendations (100% vs. 0.0, p < 0.001) and child’s father reportedly earning adequate income to cater for the family (AOR = 12.1 (1.32–109.72, p = 0.027).

Conclusion

Motherss knowledge levels regarding infant and young child feeding recommendations had notable deficiencies although they generally had a positive attitude towards child feeding recommendations. Knowledge regarding infant and young child feeding recommendations as well as the child’s father having adequate income were important determinants of adequate diet. Nutrition education should emphasize on improving mothers’ nutrition knowledge regarding infant and young child feeding recommendations and supporting mothers to overcome barriers to feed their children with adequate diets.
Choroidal vascularization and adrenergic innervation qualitative findings obtained with induced fluorescence preparations and optical coherence tomography angiography: possible correlations and perspectives
Authors: Nuzzi Raffaele , Tridico Federico , Marchese Alessandro , Bandello Francesco
Published: November 2020

Background

Recent advances in optical coherence tomography (OCT) technology allow a more accurate choroidal visualization. The aim of this study is to provide histochemical analysis with induced fluorescence images of the choroidal stromal, vascular and nerve network, highlighting possible correspondences with OCT and OCT angiography (OCT-A) analysis.

Methods

The material examined with a histochemical process of induced fluorescence through condensation of biologically active monoamines with glyoxylic acid was obtained from 6 eyes enucleated for malignant melanoma and ciliary body neoplasia. The resulting images have been qualitatively compared with OCT and OCT-A choroidal images obtained from 10 volunteers, in order to identify possible relationships. Choriocapillary segmentation was performed automatically through the embedded analysis software, while segmentation of Sattler’s and Haller’s layers was performed through a manual method.

Results

Histochemical analysis provided accurate visualization of choroidal adrenergic innervation across all layers and its relationships with blood vessels and melanocytes. The above structures were not visualized at OCT and OCT-A which provided good visualization of blood vessels in Sattler’s and Haller’s layers as well-delimited hyporeflective areas. Decorrelation signal was not detected in OCT-A analysis due to low blood flow velocity in external choroidal layers.

Conclusions

The choroid is an extremely dynamic structure which deserves to be analyzed in vivo since it is involved in the pathogenesis of several ocular conditions. Direct evaluation of the activity of choroidal nerves and melanocytes is still not possible with OCT and OCT-A, even if they are capable of providing a satisfactory representation of choroidal vascularization.
18F-FDG-PET/CT in radiation therapy-induced parotid gland inflammation
Authors: Mouminah Alaa , Borja Austin J. , Hancin Emily C. , Chang Yu Cheng , Werner Thomas J. , Swisher-McClure Samuel , Korostoff Jonathan , Alavi Abass , Revheim Mona-Elisabeth
Published: November 2020

Background

18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is used in the clinical management of oncologic and inflammatory pathologies. It may have utility in detecting radiotherapy (RT)-induced damage of oral tissues. Thus, the aim of the present study was to use FDG-PET/CT to evaluate parotid gland inflammation following RT in patients with head and neck cancer (HNC).

Methods

This retrospective study included patients with HNC treated with photon, proton, or combined photon/proton RT, in addition to chemotherapy. All patients received FDG-PET/CT imaging pre-treatment and 3 months post-treatment. The average mean standardized uptake value (Avg SUVmean) and the average maximum standardized uptake value (Avg SUVmax) of the left and right parotid glands were determined by global assessment of FDG activity using OsiriX MD software. A two-tailed paired t test was used to compare Avg SUVmean and Avg SUVmax pre- and post-RT.

Results

Forty-seven HNC patients were included in the study. Parotid gland Avg SUVmean was significantly higher at 3 months post-treatment than pre-treatment (p < 0.05) in patients treated with photon RT, but no significant differences were found between pre- and post-treatment Avg SUVmean in patients treated with proton RT or combined photon/proton RT.

Conclusion

Our results suggest that photon RT may cause radiation-induced inflammation of the parotid gland, and that proton RT, which distributes less off-target radiation, is a safer treatment alternative.
Urinary soluble VCAM-1 is a useful biomarker of disease activity and treatment response in lupus nephritis
Authors: Gasparin Andrese Aline , de Andrade Nicole Pamplona Bueno , Hax Vanessa , Palominos Penélope Esther , Siebert Marina , Marx Romulo , Schaefer Pedro Guilherme , Veronese Francisco Veríssimo , Monticielo Odirlei André
Published: November 2020

Introduction

Vascular cell adhesion molecule-1 (VCAM-1) is involved in the progression of glomerular and tubulointerstitial injury in lupus nephritis (LN) and can be easily assessed in urine. The aim of this study was to assess urinary soluble VCAM-1 (uVCAM-1) as a biomarker of disease activity and treatment response in LN.

Methods

This prospective study enrolled 62 patients with class III, IV or V LN diagnosed within the last 3 years and divided them in two groups: with and without active nephritis at the inclusion, each group with 31 patients. At each visit, a urine sample was collected for uVCAM-1 evaluation and the nephritis status was assessed.

Results

Median uVCAM-1 level was elevated in patients with active compared to inactive LN (P < 0.001). The ROC curve of uVCAM-1 demonstrated an AUC of 0.84 and a cutoff of 47.2 ng/mgCr yielded a good sensitivity (74.2%) and specificity (74.2%) for the diagnosis of active LN. A significant correlation was found between uVCAM-1 level and renal activity scores and traditional biomarkers of LN. The level of uVCAM-1 dropped in patients with active LN who went into remission (P < 0.001), increased in patients who went into activity (P = 0.002) and did not change in patients who remained inactive (P = 0.797). The level of uVCAM-1 peaked during the flare of LN (P < 0.05).

Conclusion

The uVCAM-1 is a reliable biomarker that reflects renal disease activity and is useful for monitoring individual patients with lupus nephritis over time.
Can mean ADC value and ADC ratio of benign prostate tissue to prostate cancer assist in the prediction of clinically significant prostate cancer within the PI-RADSv2 scoring system?
Authors: Ragheb Samar Ramzy , Bassiouny Reem Hassan
Published: November 2020

Background

The aim of this study is to investigate whether quantitative DW metrics can provide additive value to the reliable categorization of lesions within existing PI-RADSv2 guidelines. Fifty-eight patients with clinically suspicious prostate cancer who underwent PR examination, PSA serum levels, sextant TRUS-guided biopsies, and bi-parametric MR imaging were included in the study.

Results

Sixty-six lesions were detected by histopathological analysis of surgical specimens. The mean ADC values were significantly lower in tumor than non-tumor tissue. The mean ADC value inversely correlated with Gleason score of tumors with a significant p value < 0.001.Conversely, a positive relationship was found between the ADC ratio (ADC of benign prostatic tissue to prostate cancer) and the pathologic Gleason score with a significant elevation of the ADC ratio along with an increase of the pathologic Gleason score (p < 0.001). ROC curves constructed for the tumor ADC and ADC ratio helped to distinguish pathologically aggressive (Gleason score ≥ 7) from non-aggressive (Gleason score ≤ 6) tumors and to correlate it with PIRADSv2 scoring to predict the presence of clinically significant PCA (PIRADSv2 DW ≥ 4). The ability of the tumor ADC and ADC ratio to predict highly aggressive tumors (GS> 7) was high (AUC for ADC and ADC ratio, 0.946 and 0.897; p = 0.014 and 0.039, respectively). The ADC cut-off value for GS ≥ 7 was < 0.7725 and for GS ≤ 6 was > 0.8620 with sensitivity and specificity 97 and 94%. The cutoff ADC ratio for predicting (GS > 7) was 1.42 and for GS ≤ 6 was > 1.320 with sensitivity and specificity 97 and 92%. By applying this ADC ratio cut-off value the sensitivity and specificity of reader 1 for correct categorization of PIRADSv2 DW > 4 increased from 90 and 68% to 95 and 90% and that of reader 2 increased from 94 and 88% to 97 and 92%, respectively.

Conclusion

Estimation of DW metrics (ADC and ADC ratio between benign prostatic tissue and prostate cancer) allow the non-invasive assessment of biological aggressiveness of prostate cancer and allow reliable application of the PIRADSv2 scoring to determine clinically significant cancer (DW score > 4) which may contribute in planning initial treatment strategies.
Study of cognitive functions in major idiopathic interstitial pneumonias
Authors: Zakaria Mohamed W. , El-Korashy Reem I. , Shaheen Mostafa O. , Selim Samah , Amum Kwashi J.
Published: November 2020

Background

Cognitive dysfunction in idiopathic interstitial pneumonia (IIP) is an important clinical co-morbidity that is associated with impaired lung function. The aim of the work is to assess cognitive function in major IIP and to find out the relation between cognitive dysfunction and the oxygenation parameters.

Results

Fifty individuals were involved in the study; 30 patients with major IIP and 20 healthy individuals. Patients with IIP had significantly lower mini mental state examination (MMSE) score compared to the control group (P < 0.001). Wechsler Deterioration Index (WDI) revealed that 33.3% (n = 10) of the patients with IIP had sure cognitive impairment and 26.6% (n = 8) had ongoing cognitive deterioration. Patients with idiopathic pulmonary fibrosis (IPF) had lower cognitive function than other IIP.

Conclusion

There is an impairment of cognitive function in patients with major IIP, particularly in IPF, as measured by WDI and MMSE. Further large studies are needed to assess the possible predictors of cognitive impairment and their effects on the patients’ outcome.
Low dose of emetine as potential anti-SARS-CoV-2 virus therapy: preclinical in vitro inhibition and in vivo pharmacokinetic evidences
Authors: Wang Aoli , Sun Yong , Liu Qingwang , Wu Hong , Liu Juan , He Jun , Yu Junling , Chen Qing Qing , Ge Yinglu , Zhang Zhuhui , Hu Chen , Chen Cheng , Qi Ziping , Zou Fengming , Liu Feiyang , Hu Jie , Zhao Ming , Huang Tao , Wang Beilei , Wang Li , Wang Wei , Wang Wenchao , Ren Tao , Liu Jing , Sun Yehuan , Fan Song , Wu Qibing , Liang Chaozhao , Sun Liangdan , Su Bin , Wei Wei , Liu Qingsong
Published: November 2020

The global pandemic of COVID-19 has attracted extensive drug searching interets for the new coronavirus SARS-CoV-2. Although currently several of clinically used “old” drugs have been repurposed to this new disease for the urgent clinical investigation, there is still great demand for more effective therapies for the anti-infections. Here we report the discovery that an “old” drug Emetine could potently inhibit SARS-CoV-2 virus replication and displayed virus entry blocking effect in Vero cells at low dose. In addition, Emetine could significantly reduce the lipopolysaccharide (LPS) induced interleukin-6 (IL-6) protein level and moderately reduce the tumor necrosis factor (TNF-α) protein level in the M1 polarized THP-1 macrophages. In vivo animal pharmacokinetics (PK) study revealed that Emetine was enriched in the lung tissue and had a long retention time (over 12 h). With 1 mg/kg single oral dose, the effective concentration of Emetine in lung was up to 1.8 μM (mice) and 1.6 μM (rats) at 12 h, which is over 200-fold higher than the EC50 of the drug. The potent in vitro antiviral replication efficacy and the high enrichment in target tissue, combining with the well documented safety profiles in human indicate that low dose of Emetine might be a potentially effective anti-SARS-CoV-2 infection therapy.
Role of Gut Microbiota in the Skeletal Response to PTH
Authors: Pacifici Roberto
Published: November 2020

Exposed surfaces of mammals are colonized with 100 trillion indigenous bacteria, fungi, and viruses, creating a diverse ecosystem known as the human microbiome. The gut microbiome is the richest microbiome and is now known to regulate postnatal skeletal development and the activity of the major endocrine regulators of bone. Parathyroid hormone (PTH) is one of the bone-regulating hormone that requires elements of the gut microbiome to exert both its bone catabolic and its bone anabolic effects. How the gut microbiome regulates the skeletal response to PTH is object of intense research. Involved mechanisms include absorption and diffusion of bacterial metabolites, such as short-chain fatty acids, and trafficking of immune cells from the gut to the bone marrow. This review will focus on how the gut microbiome communicates and regulates bone marrow cells in order to modulate the skeletal effects of PTH.
Fantastic Primeval Beings and Their Roles in Reconstructions of Indigenous Colonial Cosmologies from the Eastern Andes of Colombia
Authors: Patiño-Contreras Alejandro
Published: November 2020

This article addresses the roles of fantastic primeval beings in foundational aboriginal narratives collected in writing by Spanish friars during campaigns of conversion in the Eastern Andes of Colombia during the sixteenth and seventeenth centuries CE. This article argues that fantastic creatures are not mere fiction or propaganda. On the contrary, these characters constitute key cultural referents that play essential roles in shaping and bringing into existence society and cosmos in indigenous cosmologies during the colonial period. Foremost, these characters are rendered as necessary to deliver the colonial world into existence.
Stable tug-of-war between kinesin-1 and cytoplasmic dynein upon different ATP and roadblock concentrations
Authors: Monzon Gina A. , Scharrel Lara , DSouza Ashwin , Henrichs Verena , Santen Ludger , Diez Stefan
Published: November 2020

The maintenance of intracellular processes, like organelle transport and cell division, depend on bidirectional movement along microtubules. These processes typically require kinesin and dynein motor proteins, which move with opposite directionality. Because both types of motors are often simultaneously bound to the cargo, regulatory mechanisms are required to ensure controlled directional transport. Recently, it has been shown that parameters like mechanical motor activation, ATP concentration and roadblocks on the microtubule surface differentially influence the activity of kinesin and dynein motors in distinct manners. However, how these parameters affect bidirectional transport systems has not been studied. Here, we investigate the regulatory influence of these three parameters using in vitro gliding motility assays and stochastic simulations. We find that the number of active kinesin and dynein motors determines the transport direction and velocity, but that variations in ATP concentration and roadblock density have no significant effect. Thus, factors influencing the force balance between opposite motors appear to be important, whereas the detailed stepping kinetics and bypassing capabilities of the motors only have a small effect.
Rightward shift of optimal fascicle length with decreasing voluntary activity level in the soleus and lateral gastrocnemius muscles
Authors: Hessel Anthony L. , Raiteri Brent J. , Marsh Michael J. , Hahn Daniel
Published: November 2020

Much of our understanding of in vivo skeletal muscle properties is based on studies performed under maximal activation, which is problematic because muscles are rarely activated maximally during movements such as walking. Currently, force-length properties of the human triceps surae at submaximal voluntary muscle activity levels are not characterized. We therefore evaluated plantar flexor torque/force-ankle angle and torque/force-fascicle length properties of the soleus and lateral gastrocnemius muscles during voluntary contractions at three activity levels: 100, 30, and 22% of maximal voluntary contraction. Soleus activity levels were controlled by participants via real-time electromyography feedback and contractions were performed at ankle angles ranging from 10° plantar flexion to 35° dorsiflexion. Using dynamometry and ultrasound imaging, torque-fascicle length curves of the soleus and lateral gastrocnemius muscles were constructed. The results indicate that small muscle activity reductions shift the torque/force-angle and torque/force-fascicle length curves of these muscles to more dorsiflexed ankle angles and longer fascicle lengths (from 3 to 20% optimal fascicle length, depending on ankle angle). The shift in the torque- and force-fascicle length curves during submaximal voluntary contraction have potential implications for human locomotion (e.g. walking) as the operating range of fascicles shifts to the ascending limb, where muscle force capacity is reduced by at least 15%. These data demonstrate the need to match activity levels during construction of the torque- and force-fascicle length curves to activity levels achieved during movement to better characterize the lengths that muscles operate at relative to their optimum during a specific task.
Discounts and Deadlines in Consumer Search
Authors: Coey Dominic , Larsen Bradley J. , Platt Brennan C.
Published: November 2020

We present a new equilibrium search model where consumers initially search among discount opportunities, but are willing to pay more as a deadline approaches, eventually turning to full-price sellers. The model predicts equilibrium price dispersion and rationalizes discount and full-price sellers coexisting without relying on ex ante heterogeneity. We apply the model to online retail sales via auctions and posted prices, where failed attempts to purchase reveal consumers' reservation prices. We find robust evidence supporting the theory. We quantify dynamic search frictions arising from deadlines and show how, with deadline-constrained buyers, seemingly neutral platform fee increases can cause large market shifts. (JEL D11, D44, D83, L81)
Φιλελευθερισμός και Σοσιαλισμός: Συγκλίσεις στην πολιτική φιλοσοφία των J. S. Mill και Κ. Καστοριάδη
Authors: Ταγκούλης Νίκος
Published: November 2020

Δεν διατίθεται περίληψη
Οι Εγγενείς Ηθικές Αξίες στη Βαθιά Οικολογία και τη Θεωρία της Βιώσιμης Ανάπτυξης
Authors: Τσερώνη Αλέξα
Published: November 2020

Δεν διατίθεται περίληψη
Σωκρατικοί απόηχοι στον Αρίστιππο τον Κυρηναίο και τον Γρηγόρη Βλαστό: ηδονή και ακοσμικότητα
Authors: Φουρνάρος Σωτήρης
Published: November 2020

Δεν διατίθεται περίληψη
Η Ηθικότητα στις βασικές κατευθύνσεις της φιλοσοφίας του δικαίου
Authors: Γραμματικόπουλος Ευάγγελος
Published: November 2020

Δεν διατίθεται περίληψη
Ανεπαρκείς πόροι υγείας και επιπόλαιοι ασθενείς: ο παράγοντας της προσωπικής ευθύνης
Authors: Ηγουμενίδης Μιχάλης
Published: November 2020

Δεν διατίθεται περίληψη
Αναρχία: ουτοπία ή αναγκαιότητα για ελευθερία;
Authors: Θεοδώρου Ζαχαρούλα
Published: November 2020

Δεν διατίθεται περίληψη
Η επίδραση της Αριστοτελικής σκέψης στην πραγματεία του Θεοδώρου Β' Λάσκαρη, Της Φυσικής Κοινωνίας Λόγοι Έξι
Authors: Μελίδης Θεοφάνης
Published: November 2020

Δεν διατίθεται περίληψη
Σχέσεις φιλοσοφίας και μουσικής κατά τον Ε. Μουτσόπουλο
Authors: Μπαταργιάς Τριαντάφυλλος
Published: November 2020

Δεν διατίθεται περίληψη
Prevalence of plasmid-mediated AmpC beta-lactamases in Enterobacteria isolated from urban and rural folks in Uganda
Authors: Najjuka Christine F , Kateete David Patrick , Lodiongo Dennis K , Mambo Obede , Mocktar Chunderika , Kayondo William , Baluku Hannington , Kajumbula Henry M , Essack Sabiha Y , Joloba Moses L
Published: November 2020

Background: AmpC beta-lactamase-producing bacteria are associated with increased resistance to third-generation cephalosporins. Here, we describe plasmid-mediated AmpC beta-lactamase-producing enterobacteria isolated from urban and rural dwellers in Uganda.

Methods: Stool and urine from 1,448 individuals attending outpatient clinics in Kampala and two rural districts in central Uganda were processed for isolation of Escherichia coli and Klebsiella. Following antibiotic susceptibility testing, cefoxitin resistant isolates, and amoxicillin/clavulanate resistant but cefoxitin susceptible isolates, were tested for AmpC beta-lactamase production using the cefoxitin-cloxacillin double-disc synergy test. Carriage of plasmid-mediated AmpC beta-lactamase-encoding genes (pAmpC) and extended spectrum beta-lactamase (ESBL) encoding genes was determined by PCR.

Results: Nine hundred and thirty E. coli and 55 Klebsiella were recovered from the cultured samples, yielding 985 isolates investigated (one per participant). One hundred and twenty-nine isolates (13.1%, 129/985) were AmpC beta-lactamase producers, of which 111 were molecularly characterized for pAmpC and ESBL gene carriage. pAmpC genes were detected in 60% (67/111) of the AmpC beta-lactamase producers; pAmpC genes were also detected in 18 AmpC beta-lactamase non-producers and in 13 isolates with reduced susceptibility to third-generation cephalosporins, yielding a total of 98 isolates that carried pAmpC genes. Overall, the prevalence of pAmpC genes in cefoxitin resistant and/or amoxicillin/clavulanate resistant E. coli and Klebsiella was 59% (93/157) and 26.1% (5/23), respectively. The overall prevalence of pAmpC-positive enterobacteria was 10% (98/985); 16.4% (45/274) in Kampala, 6.2% (25/406) Kayunga, and 9.2% (28/305) Mpigi. Ciprofloxacin use was associated with carriage of pAmpC-positive bacteria while residing in a rural district was associated with protection from carriage of pAmpC-positive bacteria.

Conclusion: pAmpC beta-lactamase producing enterobacteria are prevalent in urban and rural dwellers in Uganda; therefore, cefoxitn should be considered during routine susceptibility testing in this setting.
Case Report: Neuroleptic malignant syndrome in a HIV-positive patient
Authors: Joseph Sibi , George Jerry , Tau Mongezi , Ibanez-Valdes Lourdes de Fatima , Dubula Thozama , Foyaca-Sibat Humberto
Published: November 2020

We report a 29-year-old, HIV-positive woman being treated with antipsychotic medication for psychosis (Clopixol 200mg intramuscularly monthly, Risperidone 2mg orally daily Haloperidol 2.5mg twice a day), who presented with neuroleptic malignant syndrome. She was also receiving lorazepam and sodium valproate. The patient was referred to our department as she had developed involuntary upper limb movements and simple permanent focal seizure on the lower part of the left hemiface. Clinically the patient had altered consciousness, autonomic dysfunction, and rigidity. Her blood tests showed elevated creatine kinase (1467U/L) but no leucocytosis. We did a thorough workup for other causes of such a presentation. A comprehensive history was taken from the family to exclude other medications used. Her cerebrospinal fluid results were average. Blood tests did not show evidence of infection or other abnormalities. Computed tomography brain was normal. The patient died a few days after the beginning of the attack, which we have also observed  in other HIV-female patients. As far as we know, it is the first report about this comorbidity reported in the medical literature.