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Abstract: Specific-heat measurements on Na0.35CoO2 ·1.3H2O show an evolution of the superconductivity, and its ultimate disappearance, with increasing sample age. An increase in pair breaking action, which occurs preferentially in an electron band with a small energy-gap, produces a shift in the relative contributions of two electron bands to the superconducting condensation. The similarity of the time scale for these changes to that recently reported for structural changes suggests a relation between the two effects and a basis for understanding the sample dependence of the properties of this material in general. [Copyright &y& Elsevier]

Integral controller is widely used in industry for its capability of endowing perfect adaptation to disturbances. To harness such capability for precise gene expression regulation, synthetic biologists have endeavoured in building biomolecular (quasi-)integral controllers, such as the antithetic integral controller. Despite demonstrated successes, challenges remain with designing the controller for improved transient dynamics and adaptation. Here, we explore and investigate the design principles of alternative RNA-based biological controllers, by modifying an antithetic integral controller with prevalently found natural feed-forward loops (FFL), to improve its transient dynamics and adaptation performance. With model-based analysis, we demonstrate that while the base antithetic controller shows excellent responsiveness and adaptation to system disturbances, incorporating the type-1 incoherent FFL into the base antithetic controller could attenuate the transient dynamics caused by changes in the stimuli, especially in mitigating the undesired overshoot in the output gene expression. Further analysis on the kinetic parameters reveals similar findings to previous studies that the degradation and transcription rates of the circuit RNA species would dominate in shaping the performance of the controllers.

Objective:  Rock-back is a reported complication following tibial plateau levelling osteotomy (TPLO), whereby tibial plateau angle (TPA) increases postoperatively. The mechanism of rock-back is not fully understood, although a recent ex vivo investigation demonstrated that osteotomy exit cut angle (ECA) and inclination of the plate in the sagittal plane might be risk factors. The purpose of this study was to explore these relationships in a clinical dog population. We hypothesized that dogs with rock-back would have a higher degree of plate inclination and downward ECA compared with those without rock-back., Materials and Methods:  Medical records and radiographs of dogs that underwent TPLO between January 2021 and January 2022 were retrospectively reviewed. TPA was recorded preoperatively, postoperatively, and at follow-up. Plate inclination, ECA, and descriptive data were collected. Observers measuring TPA were blinded to other variables. Rock-back was defined as a change in TPA ≥ 2., Results:  Ninety-five TPLO procedures met the inclusion criteria ( n  = 87 dogs). Rock-back was identified in 21% of TPLOs ( n  = 20/95). The mean increase in TPA in the rock-back group was 3.2 ± 2.6. Plate inclination and ECA were not correlated with the presence of rock-back. Descriptive variables did not have a significant correlation with rock-back., Conclusion:  Plate inclination and ECA did not have a relationship with rock-back when defined as a postoperative TPA change ≥2 degrees, in this clinical retrospective study., Competing Interests: None declared., (Thieme. All rights reserved.)

Radiological incidental findings (IFs) are previously undetected abnormalities which are unrelated to the original indication for imaging and are unexpectedly discovered. In brain magnetic resonance imaging (MRI), the prevalence of IFs is increasing. By reviewing the literature on IFs in brain MRI performed for research purposes and discussing ethical considerations of IFs, this paper provides an overview of brain IF research results and factors contributing to inconsistencies and considers how the consent process can be improved from an ethical perspective. We found that despite extensive literature regarding IFs in research MRI of the brain, there are major inconsistencies in the reported prevalence, ranging from 1.3% to 99%. Many factors appear to contribute to this broad range: lack of standardised definition, participant demographics variance, heterogenous MRI scanner strength and sequences, reporter variation and results classification. We also found significant discrepancies in the review, consent and clinical communication processes pertaining to the ethical nature of these studies. These findings have implications for future studies, particularly those involving artificial intelligence. Further research, particularly in relation to MRI brain IFs would be useful to explore the generalisability of study results., (© 2024 Royal Australian and New Zealand College of Radiologists.)

tRNA modifications help maintain tRNA structure and facilitate translation and stress response. Found in all three kingdoms of life, m 1 A tRNA modification occurs in the T loop of many tRNAs, stabilizes tertiary tRNA structure, and impacts translation. M 1 A in the T loop is reversible by three mammalian demethylase enzymes, which bypasses the need of turning over the tRNA molecule to adjust its m 1 A levels in cells. However, no prokaryotic tRNA demethylase enzyme has been identified that acts on endogenous RNA modifications. Using Streptomyces venezuelae as a model organism, we confirmed the presence and quantitative m 1 A tRNA signatures using mass spectrometry and high-throughput tRNA sequencing. We identified two RNA demethylases that can remove m 1 A in tRNA and validated the activity of a previously annotated tRNA m 1 A writer. Using single-gene knockouts of these erasers and the m 1 A writer, we found dynamic changes of m 1 A levels in many tRNAs under stress conditions. Phenotypic characterization highlighted changes in their growth and altered antibiotic production. Our identification of the first prokaryotic tRNA demethylase enzyme paves the way for investigating new mechanisms of translational regulation in bacteria.

Clustered Regions of Interspersed Palindromic Repeat (CRISPR)-based techniques have been utilized in various research areas, including agriculture, biotechnology, and medicine. With the use of a short sequence guide RNA and CRISPR-associated (Cas) protein, this technique allows for robust, site-specific manipulation of the genome, aiding researchers in making important biomedical discoveries and scientific advancements. In this review, we explored the applications of CRISPR/Cas systems in the field of parasitology for the identification and validation of novel functional genes, diagnosis of parasitic infections, reduction of parasite virulence, and the disruption of disease transmission. We also discussed how CRISPR can be used for the development of therapeutics, vaccines, and drug discovery. Furthermore, the challenges and future perspectives of this technology are also highlighted., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: Aneurysm number (An) is a novel prediction tool utilizing parameters of pulsatility index (PI) and aneurysm geometry. An has been shown to have the potential to differentiate intracranial aneurysm (IA) rupture status. The objective of this study is to investigate the feasibility and accuracy of An for IA rupture status prediction using Australian based clinical data., Methods: A retrospective study was conducted across three tertiary referral hospitals between November 2017 and November 2020 and all saccular IAs with known rupture status were included. Two sets of An values were calculated based on two sets of PI values previously reported in the literature., Results: Five hundred and four IA cases were included in this study. The results demonstrated no significant difference between ruptured and unruptured status when using An ≥1 as the discriminator. Further analysis showed no strong correlation between An and IA subtypes. The area under the curve (AUC) indicated poor performance in predicting rupture status (AUC1 = 0.55 and AUC2 = 0.56)., Conclusions: This study does not support An ≥1 as a reliable parameter to predict the rupture status of IAs based on a retrospective cohort. Although the concept of An is supported by hemodynamic aneurysm theory, further research is needed before it can be applied in the clinical setting., Advances in Knowledge: This study demonstrates that the novel prediction tool, An, proposed in 2020 is not reliable and that further research of this hemodynamic model is needed before it can be incorporated into the prediction of IA rupture status., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Microbes and enzymes play essential roles in soil and plant rhizosphere ecosystem functioning. However, fungicides and plant root secretions may impact the diversity and abundance of microbiota structure and enzymatic activities in the plant rhizosphere. In this study, we analyzed soil samples from the rhizosphere of four cannabinoid-rich hemp ( Cannabis sativa ) cultivars (Otto II, BaOx, Cherry Citrus, and Wife) subjected to three different treatments (natural infection, fungal inoculation, and fungicide treatment). DNA was extracted from the soil samples, 16S rDNA was sequenced, and data were analyzed for diversity and abundance among different fungicide treatments and hemp cultivars. Fungicide treatment significantly impacted the diversity and abundance of the hemp rhizosphere microbiota structure, and it substantially increased the abundance of the phyla Archaea and Rokubacteria. However, the abundances of the phyla Pseudomonadota and Gemmatimonadetes were substantially decreased in treatments with fungicides compared to those without fungicides in the four hemp cultivars. In addition, the diversity and abundance of the rhizosphere microbiota structure were influenced by hemp cultivars. The influence of Cherry Citrus on the diversity and abundance of the hemp rhizosphere microbiota structure was less compared to the other three hemp cultivars (Otto II, BaOx, and Wife). Moreover, fungicide treatment affected enzymatic activities in the hemp rhizosphere. The application of fungicides significantly decreased enzyme abundance in the rhizosphere of all four hemp cultivars. Enzymes such as dehydrogenase, dioxygenase, hydrolase, transferase, oxidase, carboxylase, and peptidase significantly decreased in all the four hemp rhizosphere treated with fungicides compared to those not treated. These enzymes may be involved in the function of metabolizing organic matter and degrading xenobiotics. The ecological significance of these findings lies in the recognition that fungicides impact enzymes, microbiota structure, and the overall ecosystem within the hemp rhizosphere.

Background: Complications from dental extractions may result in multiple post-operative visits and adversely affect the patient's life. Preventing complications may decrease post-operative morbidity for the individual as well as lower societal costs, such as lost time from work and healthcare costs., Objectives: This narrative review aims to assess the prevalence and factors influencing post-operative complications following tooth extraction, helping clinicians minimise the risk. Data Sources . Cross-sectional studies. Study Eligibility and Participants . Patients undergoing dental extractions. Our exclusion criteria included in vitro studies, animal studies, terminally ill patients, and tooth loss not due to dental extraction. Literature was collected from "PubMed" and "Web of Science" through search criteria based on the "PICO" framework. Twenty articles were used to formulate a prevalence table, and 156 articles were included for the factors influencing complications. Study Appraisal and Synthesis Methods . This narrative review was reported using the SANRA (a scale for the quality assessment of narrative review articles) checklist. Due to the scope of our narrative review and its associated objectives, the quality of cross-sectional studies (AXIS) will be conducted from the studies outlining the prevalence., Results: Alveolar osteitis appears to be the most prevalent post-operative complication following tooth extraction. Predisposing factors can be significant in their ability to alter the risk of postoperative complications, and clinicians should provide patient-centred care to mitigate this risk. Limitations . Due to the breadth of context, a systematic review was not feasible, as it may have introduced heterogeneity., Conclusion: This narrative review has highlighted an array of factors which can influence the prevalence of post-operative complications. Future research would benefit from individually reporting post-operative complications, reducing the heterogeneity in definitions of the complications, and including greater detail on the predisposing factors studied., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Peter Dignam et al.)

Aims: This study aimed to (i) evaluate the effectiveness of mindfulness-based interventions in improving self-efficacy, reducing stress and anxiety among peritoneal dialysis patients, and (ii) compare the most effective method of mindfulness based interventions., Methods: This randomized three-arm controlled trial recruited first-time peritoneal dialysis patients from the peritoneal dialysis outpatient clinic in Singapore. Patients were randomly allocated to either video-assisted mindfulness training, therapist-assisted mindfulness training or treatment-as-usual. All groups received 4.5 days of structured peritoneal dialysis training at the peritoneal dialysis centre, while video-assisted mindfulness training and therapist-assisted mindfulness training groups were taught additional mindfulness-based techniques. The perceived stress scale, self-efficacy, and anxiety (State and Trait Anxiety Inventory) were measured at baseline, 4- and 12 weeks post-randomization, using reliable and valid instruments., Results: Thirty-nine patients were recruited (13 in each group). All the therapies showed a significant time trend in anxiety. Only therapist- and video-assisted mindfulness training showed a significant trend in perceived stress scale scores but not treatment-as-usual. All Intervention X Time interactions were not significant. Patients in therapist- and video-assisted mindfulness training groups had reduced perceived stress scale scores compared to treatment-as-usual at week 12., Conclusion: This study demonstrated the potential of mindfulness-based interventions in reducing stress among first-time PD patients., (© 2024 John Wiley & Sons Australia, Ltd.)

Individuals with kidney failure undergoing maintenance dialysis frequently report a high symptom burden that can interfere with functioning and diminish life satisfaction. Until recently, the focus of nephrology care for dialysis patients has been related primarily to numerical targets for laboratory measures, and outcomes such as cardiovascular disease and mortality. Routine symptom assessment is not universal or standardized in dialysis care. Even when symptoms are identified, treatment options are limited and are initiated infrequently, in part because of a paucity of evidence in the dialysis population and the complexities of medication interactions in kidney failure. In May of 2022, Kidney Disease: Improving Global Outcomes (KDIGO) held a Controversies Conference-Symptom-Based Complications in Dialysis-to identify the optimal means for diagnosing and managing symptom-based complications in patients undergoing maintenance dialysis. Participants included patients, physicians, behavioral therapists, nurses, pharmacists, and clinical researchers. They outlined foundational principles and consensus points related to identifying and addressing symptoms experienced by patients undergoing dialysis and described gaps in the knowledge base and priorities for research. Healthcare delivery and education systems have a responsibility to provide individualized symptom assessment and management. Nephrology teams should take the lead in symptom management, although this does not necessarily mean taking ownership of all aspects of care. Even when options for clinical response are limited, clinicians should focus on acknowledging, prioritizing, and managing symptoms that are most important to individual patients. A recognized factor in the initiation and implementation of improvements in symptom assessment and management is that they will be based on locally existing needs and resources., (Copyright © 2023 Kidney Disease: Improving Global Outcomes (KDIGO). Published by Elsevier Inc. All rights reserved.)

Objective: To determine the influence of extreme brachycephalic conformation on presenting signs, imaging findings, intraoperative and perioperative complications following total ear canal ablation and lateral bulla osteotomy (TECA-LBO)., Study Design: Cross-sectional retrospective study., Animals: A total of 306 (n = 242 dogs) TECA-LBOs (extreme brachycephalic breeds [EBB] = 81, other breeds [OB] = 225)., Methods: Medical records of patients undergoing TECA-LBO at a single referral institution (2010-2022) were evaluated., Results: Extreme brachycephalic breeds most commonly presented acutely, at a younger age with oto-neurological signs (46/81, 56.8%). Chronic otitis externa without neurological signs (171/225, 76.0%) was most common in OBs. Extreme brachycephalic breeds preoperatively presented more frequently with facial nerve paresis (p = .001), vestibular syndrome (p = .001), and Horner's syndrome (p = .002) compared to OBs. On diagnostic imaging, bilateral changes (p = .038), aural masses (p = .045), para-aural abscesses (p = .011), otitis interna (p = .001), and brainstem changes (p = .001) were more common in EBBs. The apparent difference in intraoperative complication rate between EBBs (9/81, 11.1%) and OBs (12/225, 5.3%) did not reach statistical significance (p = .078). Perioperative complications occurred in 85/306 (27.8%) of TECA-LBOs with no difference in perioperative complication rate between EBBs (19/81, 23.5%) and OBs (66/225, 29.3%) (p = .586)., Conclusion: Extreme brachycephalic breeds are more likely to present for TECA-LBO acutely, with neurological signs and more advanced diagnostic imaging abnormalities. Intra- and perioperative complication rates did not differ between EBBs and OBs., Clinical Significance: Despite being subjectively more technically challenging, TECA-LBO did not result in more surgical complications in EBBs. Reported data are useful for effectively informing clients of the specific risks of TECA-LBO surgery., (© 2023 The Authors. Veterinary Surgery published by Wiley Periodicals LLC on behalf of American College of Veterinary Surgeons.)

Background: Effective interventions during the coronavirus disease 2019 (COVID-19) pandemic require an understanding of patients' knowledge and perceptions that influence their behaviour. Our study assessed knowledge of COVID-19 among kidney transplant recipients and donors, hitherto unevaluated., Methods: We conducted a cross-sectional survey among 325 kidney transplant recipients and 172 donors between 1 May 2020 and 30 June 2020. The survey questionnaire assessed knowledge levels of COVID-19, sociodemographic data, health status, psychosocial impact of COVID-19 and precautionary behaviours during the pandemic., Results: The mean COVID-19 knowledge score of the study population was 7.5 (standard deviation: 2.2) out of 10. The mean score was significantly higher among kidney recipients compared to kidney donors (7.9 [1.9] vs. 6.7 [2.6]; P <0.001). Younger age (21-49 vs. ≥50 years) and higher education (diploma and higher vs. secondary and lower) were associated with significantly higher knowledge scores in donors, but not among recipients (P-interactions ≤0.01). In both kidney recipients and donors, financial concerns and/or social isolation were associated with lower knowledge levels., Conclusions: Concerted efforts are needed to improve COVID-19 knowledge in kidney transplant recipients and donors, particularly older donors, donors with lower education and patients with financial concerns or feelings of social isolation. Intensive patient education may mitigate the impact of education levels on COVID-19 knowledge levels., Competing Interests: None

Chemical reaction networks can be utilised as basic components for nucleic acid feedback control systems' design for Synthetic Biology application. DNA hybridisation and programmed strand-displacement reactions are effective primitives for implementation. However, the experimental validation and scale-up of nucleic acid control systems are still considerably falling behind their theoretical designs. To aid with the progress heading into experimental implementations, we provide here chemical reaction networks that represent two fundamental classes of linear controllers: integral and static negative state feedback. We reduced the complexity of the networks by finding designs with fewer reactions and chemical species, to take account of the limits of current experimental capabilities and mitigate issues pertaining to crosstalk and leakage, along with toehold sequence design. The supplied control circuits are quintessential candidates for the first experimental validations of nucleic acid controllers, since they have a number of parameters, species, and reactions small enough for viable experimentation with current technical capabilities, but still represent challenging feedback control systems. They are also well suited to further theoretical analysis to verify results on the stability, performance, and robustness of this important new class of control systems.

The rise of antimicrobial resistance is a global public health crisis that threatens the effective control and prevention of infections. Due to the emergence of pandrug-resistant bacteria, most antibiotics have lost their efficacy. Bacteriophages or their components are known to target bacterial cell walls, cell membranes, and lipopolysaccharides (LPS) and hydrolyze them. Bacteriophages being the natural predators of pathogenic bacteria, are inevitably categorized as "human friends", thus fulfilling the adage that "the enemy of my enemy is my friend". Leveraging on their lethal capabilities against pathogenic bacteria, researchers are searching for more ways to overcome the current antibiotic resistance challenge. In this study, we expressed and purified epsilon 34 phage tailspike protein (E34 TSP) from the E34 TSP gene, then assessed the ability of this bacteriophage protein in the killing of two CBD-resistant strains of Salmonella spp. We also assessed the ability of the tailspike protein to cause bacteria membrane disruption, and dehydrogenase depletion. We observed that the combined treatment of CBD-resistant strains of Salmonella with CBD and E34 TSP showed poor killing ability whereas the monotreatment with E34 TSP showed considerably higher killing efficiency. This study demonstrates that the inhibition of the bacteria by E34 TSP was due in part to membrane disruption, and dehydrogenase inactivation by the protein. The results of this work provides an interesting background to highlight the crucial role phage protein such as E34 TSP could play in pathogenic bacterial control., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ibrahim, Ayariga, Xu, Adebanjo, Robertson, Samuel-Foo and Ajayi.)

Objective: This is a study on the demographics and clinical outcomes including the response to therapy of patients with focal segmental glomerulosclerosis (FSGS) over the past decade., Materials and Methods: All histologically proven FSGS cases diagnosed between 2008 and 2018 were analyzed for their clinical, laboratory, and histological characteristics including treatment that could influence the disease progression and renal outcome of these patients. We used the Columbia Classification for FSGS for the renal biopsy., Results: There were two subgroups of FSGS patients; those with nephrotic syndrome and those without nephrotic syndrome. Patients with FSGS with non-nephrotic syndrome had poorer survival rates compared to the nephrotic group. For those without nephrotic syndrome, the indices responsible for progression involved more tubular and blood vessel lesions in addition to glomerular pathology compared to those with nephrotic syndrome. Patients with FSGS with nephrotic syndrome responded to immunosuppressants more favorably compared to the non-nephrotic group, though both groups responded with decreasing proteinuria. The nephrotic group had a better 10-year long-term survival rate of 92 vs. 72% for the non-nephrotic group (log-rank 0.002). The 10-year survival for the whole group of FSGS patients was 64%., Conclusion: Our data suggest that in FSGS, one of the significant components of the disease is the vascular and tubular damage, apart from the underlying glomerular pathology, resulting in varying responses to therapy, and the difference is reflected in inherently poorer response to immunosuppressant therapy in those without nephrotic syndrome as opposed to those with nephrotic syndrome, who responded to immunosuppressant therapy (IST) with stabilization of renal function and had less blood vessel and tubular lesions.

This systematic review and meta-analysis aimed to examine more recent data to determine the extent of lingual nerve injury (LNI) following the surgical extraction of mandibular third molars (M3M). A systematic search of three databases [PubMed, Web of Science and OVID] was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The inclusion criteria encompassed studies on patients who underwent surgical M3M extraction using the buccal approach without lingual flap retraction (BA-), buccal approach with lingual flap retraction (BA+), and lingual split technique (LS). The outcome measures expressed in LNI count were converted to risk ratios (RR). Twenty-seven studies were included in the systematic review, nine were eligible for meta-analysis. Combined RR for LNI (BA+ versus BA-) was 4.80 [95% Confidence Interval:3.28-7.02; P<0.00001]. The prevalence of permanent LNI following BA-, BA+ and LS (mean%±SD%) was 0.18±0.38, 0.07±0.21, and 0.28±0.48 respectively. This study concluded that there was an increased risk of temporary LNI following M3M surgical extractions using BA+ and LS. There was insufficient evidence to determine whether there is a significant advantage of BA+ or LS in reducing permanent LNI risk. Operators should use lingual retraction with caution due to the increased temporary LNI risk., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

There is a growing interest in the use of alternative medical systems (AMS), such as traditional Chinese medicine (TCM), ayurveda, homeopathy, and naturopathy, among chronic kidney disease patients. This review summarizes the efficacy and safety of AMS interventions in chronic kidney disease (CKD) patients. A systematic review was conducted in MEDLINE, Embase, Scopus, CINAHL, CENTRAL, and PsycINFO in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Synthesis without meta-analysis (SWiM) guidelines. Randomized controlled trials (RCTs) which evaluated the use of AMS among adult CKD patients were included. The efficacy of each AMS was assessed based on improvement in biochemical markers or reduction in symptom severity scores. All adverse reactions were recorded. Of the 14,583 articles retrieved, 33 RCTs were included. TCM (n=20) and ayurveda (n=6) were the most well-studied. Majority of studies (66.7%) had a sample size <100. Common indications evaluated included improvement in renal function (n=12), proteinuria (n=5), and uremic pruritus (n=5). Among TCM, acupuncture and syndromes-based TCM granules formulation were shown to improve estimated glomerular filtration rate (eGFR) by 5.1-15.5% and 7.07-8.12% respectively. Acupuncture reduced uremic pruritus symptoms by 54.7-60.2% while Huangkui, Shenqi granules, and Tripterygium wilfordii Hook F reduced proteinuria by 18.6-50.7%, 61.8%, and 32.1% respectively. For Ayurveda, camel milk and Nigella sativa oil improved eGFR by 16.9% and 86.8%, respectively, while capsaicin reduced pruritus scores by 84.3%. Homeopathic verum medication reduced pruritus scores by 29.2-41.5%. Nausea was the most common adverse effect reported with alpha-keto amino acids (0.07%), Nigella sativa oil (7.04%), and silymarin (10%). TCM and ayurveda were more well-studied AMS therapies that demonstrated efficacy in CKD patients. RCTs with larger sample sizes are needed to ascertain the efficacy and safety of promising AMS., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Teo et al.)

New generation antibiotics are needed to combat the development of resistance to antimicrobials. One of the most promising new classes of antibiotics is cannabidiol (CBD). It is a non-toxic and low-resistance chemical that can be used to treat bacterial infections. The antibacterial activity of Cannabis sativa L. byproducts, specifically CBD, has been of growing interest in the field of novel therapeutics. As research continues to define and characterize the antibacterial activity that CBD possesses against a wide variety of bacterial species, it is important to examine potential interactions between CBD and common therapeutics such as broad-spectrum antibiotics. In this study it is demonstrated that CBD-antibiotic (combination of CBD and antibiotic) co-therapy can effectively fight Salmonella typhimurium ( S. typhimurium ) via membrane integrity disruption. This research serves to examine the potential synergy between CBD and three broad-spectrum antibiotics (ampicillin, kanamycin, and polymyxin B) for potential CBD-antibiotic co-therapy. In this study, it is revealed that S. typhimurium growth is inhibited at very low dosages of CBD-antibiotic. This interesting finding demonstrates that CBD and CBD-antibiotic co-therapies are viable novel alternatives to combating S. typhimurium .

Hand-eye calibration is an important step in controlling a vision-guided robot in applications like part assembly, bin picking and inspection operations etc. Many methods for estimating hand-eye transformations have been proposed in literature with varying degrees of complexity and accuracy. However, the success of a vision-guided application is highly impacted by the accuracy the hand-eye calibration of the vision system with the robot. The level of this accuracy depends on several factors such as rotation and translation noise, rotation and translation motion range that must be considered during calibration. Previous studies and benchmarking of the proposed algorithms have largely been focused on the combined effect of rotation and translation noise. This study provides insight on the impact of rotation and translation noise acting in isolation on the hand-eye calibration accuracy. This deviates from the most common method of assessing hand-eye calibration accuracy based on pose noise (combined rotation and translation noise). We also evaluated the impact of the robot motion range used during the hand-eye calibration operation which is rarely considered. We provide quantitative evaluation of our study using six commonly used algorithms from an implementation perspective. We comparatively analyse the performance of these algorithms through simulation case studies and experimental validation using the Universal Robot's UR5e physical robots. Our results show that these different algorithms perform differently when the noise conditions vary rather than following a general trend. For example, the simultaneous methods are more resistant to rotation noise, whereas the separate methods are better at dealing with translation noise. Additionally, while increasing the robot rotation motion span during calibration enhances the accuracy of the separate methods, it has a negative effect on the simultaneous methods. Conversely, increasing the translation motion range improves the accuracy of simultaneous methods but degrades the accuracy of the separate methods. These findings suggest that those conditions should be considered when benchmarking algorithms or performing a calibration process for enhanced accuracy., Competing Interests: The authors have declared that no competing interests exist.

Objective: PSMA PET/CT has demonstrated superior sensitivity over conventional imaging in the detection of local and distant recurrence in biochemically relapsed (BCR) prostate cancer. We prospectively investigated the management impact of 68 Ga-PSMA PET/CT imaging in men with BCR, with the aim of identifying baseline clinicopathological predictors for management change., Patients and Methods: Men with BCR who met eligibility criteria underwent 68 Ga-PSMA-11 PET/CT at Monash Health (Melbourne, Australia). Intended management plans were prospectively documented before and after 68 Ga-PSMA PET/CT imaging. Binary logistic regression analysis was performed to identify potential clinicopathological predictors of management change. Descriptive statistics were used to characterize the nature of these changes., Results: Seventy men underwent 68 Ga-PSMA-11 PET/CT imaging. Median age was 67 years (IQR 63-72) and median PSA was 0.48 ng/ml (IQR 0.21-1.9). PSMA-avid disease was observed in 56% (39/70) of patients. Pre-scan management plan was altered following scanning in 43% (30/70) of patients. Management changes were significantly more common in patients with higher baseline PSA levels (PSA≥2 ng/ml, p = 0.01). 18/36 (50%) of the patients initially planned for watchful waiting had their management changed, including the use of salvage pelvic radiotherapy (n = 7) and stereotactic ablative body radiotherapy to oligometastatic disease (n = 6)., Conclusion: Management change after 68 Ga-PSMA PET/CT for BCR is common and typically resulted in treatment intensification strategies in those planned for a watchful waiting approach. This study adds to the growing pool of evidence supporting the clinical utility of PSMA PET/CT imaging in the care of patients with BCR after definitive therapy., (© 2021 John Wiley & Sons Australia, Ltd.)

Recent advances in synthetic biology have enabled the design of genetic feedback control circuits that could be implemented to build resilient plants against pathogen attacks. To facilitate the proper design of these genetic feedback control circuits, an accurate model that is able to capture the vital dynamical behaviour of the pathogen-infected plant is required. In this study, using a data-driven modelling approach, we develop and compare four dynamical models (i.e. linear, Michaelis-Menten with Hill coefficient (Hill Function), standard S-System and extended S-System) of a pathogen-infected plant gene regulatory network (GRN). These models are then assessed across several criteria, i.e. ease of identifying the type of gene regulation, the predictive capability, Akaike Information Criterion (AIC) and the robustness to parameter uncertainty to determine its viability of balancing between biological complexity and accuracy when modelling the pathogen-infected plant GRN. Using our defined ranking score, we obtain the following insights to the modelling of GRN. Our analyses show that despite commonly used and provide biological relevance, the Hill Function model ranks the lowest while the extended S-System model ranks highest in the overall comparison. Interestingly, the performance of the linear model is more consistent throughout the comparison, making it the preferred model for this pathogen-infected plant GRN when considering data-driven modelling approach., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: In advanced chronic kidney disease (CKD), patients face complex decisions related to renal replacement modality that can cause decisional conflict and delay. This study aimed to evaluate the prevalence of severe decisional conflict across decision types and to identify the psychosocial and clinical factors associated with decisional conflict in this population., Design: Observational cross-sectional study., Methods: Patients with CKD in renal care were recruited. The Decisional Conflict Scale (DCS), Functional, Communicative, and Critical Health Literacy (FCCHL), Health Literacy Questionnaire (HLQ), Hospital Anxiety and Depression Scale (HADS), Brief Illness Perception Questionnaire (BIPQ), and the Kidney-disease Quality of Life (KDQOL) questionnaires were used. Clinical data were obtained from medical records. Bivariate and multivariable logistic regression models were used to identify predictors of severe decisional conflict (DCS score ≥ 37.5)., Results: Participants (N = 190; response rate = 56.7%; mean age = 62.8 ± 10.8) reported moderate levels of decisional conflict (29.7 ± 14.5). The overall prevalence of severe decisional conflict was 27.5% (n = 46) with no significant differences across decision types (dialysis, modality, access). Ethnicity (Chinese), marital status (married), BIPQ treatment control, coherence, KDQOL staff encouragement, and all health literacy domains, except functional health literacy, were significant predictors of decisional conflict in the unadjusted models. In the multivariable model, only the health literacy domains of FCCHL Communicative, and HLQ Active Engagement remained significant., Conclusion: Even after pre-dialysis education, many CKD patients in this study still report severe decisional conflict, with rates remaining substantial across decision junctures. The associations of decisional conflict and health literacy skills related to communication and engagement with healthcare providers indicate that more collaborative and patient-centric pre-dialysis programs may support patient activation and resolve decisional conflict., (© 2021 British Psychological Society.)

Prostate-specific membrane antigen (PSMA) tracers have increased sensitivity in the detection of prostate cancer, compared with conventional imaging. We assessed the management impact of 18 F-DCFPyL PSMA PET/CT in patients with prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP) and report early biochemical response in patients who underwent radiation treatment. Methods: One hundred patients were enrolled into a prospective study, with a prior RP for prostate cancer, a PSA of 0.2-2.0 ng/mL, and no prior treatment. All patients underwent diagnostic CT and PSMA PET/CT, and management intent was completed at 3 time points (original, post-CT, and post-PSMA) and compared. Patients who underwent radiotherapy with 6-mo PSA response data are presented. Results: Ninety-eight patients are reported, with a median PSA of 0.32 ng/mL (95% CI, 0.28-0.36), pT3a/b disease in 71.4%, and an International Society of Urological Pathology grade group of at least 3 in 59.2%. PSMA PET/CT detected disease in 46.9% of patients, compared with 15.5% using diagnostic CT (PSMA PET, 29.2% local recurrence and 29.6% pelvic nodal disease). A major change in management intent was higher after PSMA than after CT (12.5% vs. 3.2%, P = 0.010), as was a moderate change in intent (31.3% vs. 13.7%, P = 0.001). The most common change was an increase in the recommendation for elective pelvic radiation (from 15.6% to 33.3%), nodal boost (from 0% to 22.9%), and use of concurrent androgen deprivation therapy (ADT) (from 22.9% to 41.7%) from original to post-PSMA intent because of detection of nodal disease. Eighty-six patients underwent 18 F-DCFPyL-guided radiotherapy. Fifty-five of 86 patients either did not receive ADT or recovered after ADT, with an 18-mo PSA response from 0.32 to 0.02 ng/mL; 94.5% of patients had a PSA of no more than 0.20 ng/mL, and 74.5% had a PSA of no more than 0.03 ng/mL. Conclusion: 18 F-DCFPyL PET/CT has a significant impact on management intent in patients being considered for salvage radiotherapy after RP with PSA recurrence. Increased detection of disease, particularly in the pelvic lymph nodes, resulted in increased pelvic irradiation and concurrent ADT use. Early results in patients who are staged with 18 F-DCFPyL PET/CT show a favorable PSA response., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Mathematical models are powerful tools in guiding the construction of synthetic biological circuits, given their capability of accurately capturing and predicting circuit dynamics. Recent innovations in RNA technology have enabled the development of a variety of new tools for regulating gene expression at both the transcription and translation levels. However, the effects of different regulation levels on the circuit dynamics remain largely unexplored. In this study, we focus on the type 1 incoherent feed-forward loop (I1-FFL) gene circuit with four different variations (TX, TL, HY-1, HY-2), to investigate how regulation at the transcription and translation levels affect the circuit dynamics. We develop a mechanistic model for each of the four circuits and deploy sensitivity analysis to investigate the circuits' dynamics in terms of pulse generation. Based on the analysis, we observe that the repression regulation mechanism dominates the characteristics of the pulse as compared to the activation regulation mechanism and find that the I1-FFL with transcription repression has a higher chance of generating a pulse meeting the desired criteria. The experimental results in Escherichia coli also confirm our findings from the computational analysis. We expect our findings to facilitate future experimental construction of gene circuits with insights on the selection of appropriate transcription and translation regulation tools.

Products derived from Cannabis sativa L. have gained increased interest and popularity. As these products become common amongst the public, the health and potential therapeutic values associated with hemp have become a premier focus of research. While the psychoactive and medicinal properties of Cannabis products have been extensively highlighted in the literature, the antibacterial properties of cannabidiol (CBD) have not been explored in depth. This research serves to examine the antibacterial potential of CBD against Salmonella newington and S . typhimurium . In this study, we observed bacterial response to CBD exposure through biological assays, bacterial kinetics, and fluorescence microscopy. Additionally, comparative studies between CBD and ampicillin were conducted against S . typhimurium and S . newington to determine comparative efficacy. Furthermore, we observed potential resistance development of our Salmonella spp. against CBD treatment.

tRNA is the most extensively modified RNA in cells. On average, a bacterial tRNA contains 8 modifications per molecule and a eukaryotic tRNA contains 13 modifications per molecule. Recent studies reveal that tRNA modifications are highly dynamic and respond extensively to environmental conditions. Functions of tRNA modification dynamics include enhanced, on-demand decoding of specific codons in response genes and regulation of tRNA fragment biogenesis. This review summarizes recent advances in the studies of tRNA modification dynamics in biological processes, tRNA modification erasers, and human-associated bacteria. Furthermore, we use the term "metaepitranscriptomics" to describe the potential and approach of tRNA modification studies in natural biological communities such as microbiomes. tRNA is highly modified in cells, and tRNA modifications respond extensively to environmental conditions to enhance translation of specific genes and produce tRNA fragments on demand. We review recent advances in tRNA sequencing methods, tRNA modification dynamics in biological processes, and tRNA modification studies in natural communities such as the microbiomes., Competing Interests: Declaration of interests Tao Pan is a co-founder of 4SR Biosciences., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Advances in endovascular technology have expanded the treatment options for intracranial aneurysms. Intrasaccular flow diversion is a relatively new technique that aims to disrupt blood inflow at the neck of the aneurysm, hence promoting intrasaccular thrombosis. The Woven EndoBridge device (WEB; MicroVention, Aliso Viejo, CA, USA) is an US Food and Drug Administration approved intrasaccular flow diverter for wide-necked aneurysms. We report the early interim clinical and radiological outcomes of patients with both ruptured and unruptured intracranial aneurysms (IAs) treated using the WEB device in an Australian population., Materials and Methods: A retrospective analysis was done of patients with ruptured or unruptured IAs who received treatment with WEB across 5 Australian neuroendovascular referral centers between May 2017 and November 2020. Angiographic occlusion was assessed with time-of-flight magnetic resonance angiography. Complications were recorded and clinical outcomes were assessed using the modified Rankin scale at follow-up., Results: In total, 66 aneurysms were treated in 63 patients, with successful deployment of the WEB device in 98.5% (n=65). Eighteen (26.9%) ruptured aneurysms were included. Failure of deployment occurred in a single case. Adjunct coiling and/or stenting was performed in 20.9% (n=14) cases. Sixty-two patients with 65 aneurysms using a WEB device were followed up (mean=9.1 months), and 89.4% of these had complete aneurysm occlusion while 1.5% remained patent. Functional independence was achieved in 93.5% of cases., Conclusion: Early results following the use of WEB devices in Australia demonstrate safety and adequate aneurysm occlusion comparable to international literature.

The circadian system-an organism's built-in biological clock-is responsible for orchestrating biological processes to adapt to diurnal and seasonal variations. Perturbations to the circadian system (e.g., pathogen attack, sudden environmental change) often result in pathophysiological responses (e.g., jetlag in humans, stunted growth in plants, etc.) In view of this, synthetic biologists are progressively adapting the idea of employing synthetic feedback control circuits to alleviate the effects of perturbations on circadian systems. To facilitate the design of such controllers, suitable models are required. Here, we extend our recently developed model for the plant circadian clock-termed the extended S-System model-to model circadian systems across different kingdoms of life. We then use this modeling strategy to develop a design framework, based on an antithetic integral feedback (AIF) controller, to restore a gene's circadian profile when it is subject to loss-of-function due to external perturbations. The use of the AIF controller is motivated by its recent successful experimental implementation. Our findings provide circadian biologists with a systematic and general modeling and design approach for implementing synthetic feedback control of circadian systems., (© 2022. The Author(s).)

To meet the ever-increasing global food demand, the food production rate needs to be increased significantly in the near future. Speed breeding is considered as a promising agricultural technology solution to achieve the zero-hunger vision as specified in the United Nations Sustainable Development Goal 2. In speed breeding, the photoperiod of the artificial light has been manipulated to enhance crop productivity. In particular, regulating the photoperiod of different light qualities rather than solely white light can further improve speed breading. However, identifying the optimal light quality and the associated photoperiod simultaneously remains a challenging open problem due to complex interactions between multiple photoreceptors and proteins controlling plant growth. To tackle this, we develop a first comprehensive model describing the profound effect of multiple light qualities with different photoperiods on plant growth (i.e. hypocotyl growth). The model predicts that hypocotyls elongated more under red light compared to both red and blue light. Drawing similar findings from previous related studies, we propose that this might result from the competitive binding of red and blue light receptors, primarily Phytochrome B (phyB) and Cryptochrome 1 (cry1) for the core photomorphogenic regulator, CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1). This prediction is validated through an experimental study on Arabidopsis thaliana . Our work proposes a potential molecular mechanism underlying plant growth under different light qualities and ultimately suggests an optimal breeding protocol that takes into account light quality., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Annals of Botany Company.)

Smart greenhouse farming has emerged as one of the solutions to global food security, where farming productivity can be managed and improved in an automated manner. While it is known that plant development is highly dependent on the quantity and quality of light exposure, the specific impact of the different light properties is yet to be fully understood. In this study, using the model plant Arabidopsis, we systematically investigate how six different light properties (i.e., photoperiod, light offset, intensity, phase of dawn, duration of twilight and period) would affect plant development i.e., flowering time and hypocotyl (seedling stem) elongation using an established mathematical model of the plant circadian system relating light input to flowering time and hypocotyl elongation outputs for smart greenhouse application. We vary each of the light properties individually and then collectively to understand their effect on plant development. Our analyses show in comparison to the nominal value, the photoperiod of 18 hours, period of 24 hours, no light offset, phase of dawn of 0 hour, duration of twilight of 0.05 hour and a reduced light intensity of 1% are able to improve by at least 30% in days to flower (from 32.52 days to 20.61 days) and hypocotyl length (from 1.90 mm to 1.19mm) with the added benefit of reducing energy consumption by at least 15% (from 4.27 MWh/year to 3.62 MWh/year). These findings could provide beneficial solutions to the smart greenhouse farming industries in terms of achieving enhanced productivity while consuming less energy., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Currently, there are little to no published studies outlining general dentists' knowledge in the management of patients on anticoagulant/antiplatelet therapies in Australia. The aim of this study was to investigate the current practices of Western Australian (WA) general dentists with regards to dental management of patients taking anticoagulants/antiplatelets., Materials and Methods: WA dentists were invited to undertake a survey to investigate their knowledge on the management of patients taking anticoagulant/antiplatelet. The questionnaire provided to WA general dentists consisted of pre-extraction advice on patients (direct oral anticoagulants [DOACs], antiplatelets, warfarin, dual antiplatelets and antiplatelet/anticoagulant). Results were analysed using descriptive statistics as well as chi-square tests., Results: Of the 89 participants, 40.5% had <5 years of general dental experience. Most WA general dentists (64%-71%) responded with 'no change' when performing extractions on patients on DOACs, antiplatelet therapy, warfarin, dual antiplatelets and antiplatelets/anticoagulants (P = 0.00). Furthermore, dentists with 6-10 years of experience were more likely to cease antiplatelet for 24 h before extractions (P < 0.05). Dentists who extracted 10-30 teeth per month were likely to stop antiplatelets and DOACs for more than 48 h compared to other groups (P < 0.05)., Conclusion: Most WA dentists would not cease anticoagulant/antiplatelet therapy when undergoing dental extractions., (© 2021 Australian Dental Association.)

Purpose: Carotid artery stenting (CAS) is an established treatment for symptomatic carotid artery stenosis as an alternative to carotid endarterectomy. A variety of techniques and devices have been devised to minimise periprocedural stroke risk using either proximal or distal embolic protection. This study presents a method of embolic protection during CAS-the CaRotid Artery Filtering Technique (CRAFT)., Materials and Methods: The CRAFT technique employs aspects of both proximal and distal embolic protection. The CASPER RX stent (MicroVention, Tustin, CA, USA), which is a double-layered, closed-cell, micromesh nitinol stent, is deployed across the carotid artery stenosis with the assistance of a FlowGate balloon guide catheter (Stryker Neurovascular, Fremont, CA, USA). The partially deployed stent acts as a distal filter while the balloon guide is deflated midway during stent deployment to prevent distal plaque embolisation, followed by completion of stent deployment and angioplasty., Results: A total of 94 patients underwent CAS using the CRAFT technique between June 2016 and March 2021. Successful stent deployment was achieved in all patients. Preliminary results demonstrated acute stent occlusion in 6 patients (6.4%) and distal embolic stroke in 5 patients (5.3%). The median procedural fluoroscopy time was 34 minutes with an interquartile range of 22 to 55 minutes., Conclusion: The CRAFT technique of CAS presented by this study can be applied in the treatment of symptomatic carotid artery stenosis in both emergency and elective procedure settings with a high technical success and low distal embolic stroke risk.

There has been a resurgence in the cultivation of industrial hemp, Cannabis sativa L., in the United States since its recent legalization. This may facilitate increased populations of arthropods associated with the plant. Hemp pests target highly marketable parts of the plant, such as flowers, stalks, and leaves, which ultimately results in a decline in the quality. Industrial hemp can be used for several purposes including production of fiber, grain, and cannabidiol. Thus, proper management of pests is essential to achieve a substantial yield of hemp in the face of climate change. In this review, we provide updates on various arthropods associated with industrial hemp in the United States and examine the potential impact of climate change on corn earworm (CEW) Helicoverpa zea Boddie, a major hemp pest. For example, temperature and photoperiod affect the development and diapause process in CEW. Additionally, drought can lead to a reduction in hemp growth. Host plant diversity of CEW may prevent populations of the pest from reaching outbreak levels. It is suggested that hemp varieties resistant to drought, high soil salinity, cold, heat, humidity, and common pests and diseases should be selected. Ongoing research on effective management of CEW in hemp is critical.

This clinical trial (ACTRN12619001296123) investigated the impact of silymarin (Legalon®) on circulating bilirubin concentration, lipid status, systemic inflammation, and antioxidant status. The study design was a randomized, placebo-controlled, single-blind crossover trial of healthy men (18-65 years), conducted at Griffith University, Gold Coast, Australia. Participants were recruited from Griffith University and were randomized to silymarin (140 mg silymarin capsules thrice daily) or placebo (3 capsules containing mannitol taken daily) for 14 days followed by a ≥4-week washout and crossover to the other arm. The main outcomes were whether silymarin treatment would increase serum bilirubin concentration by >0.29 mg/dL, change serum lipid status (cholesterol and triglycerides), inflammation (c-reactive protein), and antioxidant capacity (ferric reducing ability of plasma) compared with baseline. Silymarin consumption (n = 17) did not affect serum concentrations of unconjugated bilirubin (0.73 versus 0.67 mg/dL, P = .79), cholesterol (185 versus 189 mg/dL, P = .19), triglycerides (94.2 versus 92.3 mg/dL, P = .79), c-reactive protein (0.17 versus 0.09 mg/dL, P = .23), or antioxidant status (6.61 versus 6.67 mg Fe 2+ /dL, P = .40). These findings challenge previous reports and manufacturer claims of hyperbilirubinemia following silymarin treatment and are critical to guiding researchers toward an effective means to mildly elevate bilirubin, which evidence suggests could protect from cardiovascular disease., (© 2021, The American College of Clinical Pharmacology.)

Purpose: Prostate-specific membrane antigen (PSMA) PET/CT is increasingly used in patients with biochemical recurrence post prostatectomy to detect local recurrence and metastatic disease at low PSA levels. The aim of this study was to assess patterns of disease detection, predictive factors and safety using [ 18 F]DCFPyL PET/CT versus diagnostic CT in patients being considered for salvage radiotherapy with biochemical recurrence post prostatectomy., Methods: We conducted a prospective trial recruiting 100 patients with detectable PSA post prostatectomy (PSA 0.2-2.0 ng/mL) and referred for salvage radiotherapy from August 2018 to July 2020. All patients underwent a PSMA PET/CT using the [ 18 F]DCFPyL tracer and a diagnostic CT. The detection rates of [ 18 F]DCFPyL PET/CT vs diagnostic CT were compared and patterns of disease are reported. Clinical patient and tumour characteristics were analysed for predictive utility. Thirty-day post-scan safety is reported., Results: Of 100 patients recruited, 98 were suitable for analysis with a median PSA of 0.32 ng/mL. [ 18 F]DCFPyL PET/CT was positive 46.4% and equivocal 5.2%, compared to 15.5% positivity for diagnostic CT. Local recurrence was detected on [ 18 F]DCFPyL PET/CT in 28.5%, nodal disease in 27.5% and bony metastases in 6.1% of patients. Both ISUP grade group (p < 0.001) and pre-scan PSA (p = 0.029) were significant predictors of [ 18 F]DCFPyL PET/CT positivity, and logistic regression generated probabilities combining the two showed improved prediction rates. No significant safety events were reported post [ 18 F]DCFPyL administration., Conclusions: [ 18 F]DCFPyL PET/CT increases detection of disease in patients with biochemical recurrence post prostatectomy compared to diagnostic CT. Patients being considered for salvage radiotherapy with a PSA >0.2 ng/mL should be considered for [ 18 F]DCFPyL PET/CT scan., Trial Registration: Australian New Zealand Clinical Trials Registry Number: ACTRN12618001530213 ( http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375932&isReview=true )., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Epitranscriptomic mechanisms linking tRNA function and the brain proteome to cognition and complex behaviors are not well described. Here, we report bi-directional changes in depression-related behaviors after genetic disruption of neuronal tRNA cytosine methylation, including conditional ablation and transgene-derived overexpression of Nsun2 in the mouse prefrontal cortex (PFC). Neuronal Nsun2-deficiency was associated with a decrease in tRNA m 5 C levels, resulting in deficits in expression of 70% of tRNA Gly isodecoders. Altogether, 1488/5820 proteins changed upon neuronal Nsun2-deficiency, in conjunction with glycine codon-specific defects in translational efficiencies. Loss of Gly-rich proteins critical for glutamatergic neurotransmission was associated with impaired synaptic signaling at PFC pyramidal neurons and defective contextual fear memory. Changes in the neuronal translatome were also associated with a 146% increase in glycine biosynthesis. These findings highlight the methylation sensitivity of glycinergic tRNAs in the adult PFC. Furthermore, they link synaptic plasticity and complex behaviors to epitranscriptomic modifications of cognate tRNAs and the proteomic homeostasis associated with specific amino acids., (© 2021. The Author(s).)

RNA-based regulators are promising tools for building synthetic biological systems that provide a powerful platform for achieving a complex regulation of transcription and translation. Recently, de novo-designed synthetic RNA regulators, such as the small transcriptional activating RNA (STAR), toehold switch (THS), and three-way junction (3WJ) repressor, have been utilized to construct RNA-based synthetic gene circuits in living cells. In this work, we utilized these regulators to construct type 1 incoherent feed-forward loop (IFFL) circuits in vivo and explored their dynamic behaviors. A combination of a STAR and 3WJ repressor was used to construct an RNA-only IFFL circuit. However, due to the fast kinetics of RNA-RNA interactions, there was no significant timescale difference between the direct activation and the indirect inhibition, that no pulse was observed in the experiments. These findings were confirmed with mechanistic modeling and simulation results for a wider range of conditions. To increase delay in the inhibition pathway, we introduced a protein synthesis process to the circuit and designed an RNA-protein hybrid IFFL circuit using THS and TetR protein. Simulation results indicated that pulse generation could be achieved with this RNA-protein hybrid model, and this was further verified with experimental realization in E. coli . Our findings demonstrate that while RNA-based regulators excel in speed as compared to protein-based regulators, the fast reaction kinetics of RNA-based regulators could also undermine the functionality of a circuit (e.g., lack of significant timescale difference). The agreement between experiments and simulations suggests that the mechanistic modeling can help debug issues and validate the hypothesis in designing a new circuit. Moreover, the applicability of the kinetic parameters extracted from the RNA-only circuit to the RNA-protein hybrid circuit also indicates the modularity of RNA-based regulators when used in a different context. We anticipate the findings of this work to guide the future design of gene circuits that rely heavily on the dynamics of RNA-based regulators, in terms of both modeling and experimental realization.

Purpose: Low-profile, self-expandable stents have broadened therapeutic options available for definitive treatment of intracranial aneurysms. The novel Low-Profile Visualized Intraluminal Support (LVIS) EVO stent extends upon the success of its predecessor, the LVIS Jr stent, aiming to enable higher visibility and greater opening ability within a self-expandable and fully retrievable microstent system. In this study, we aim to report the early safety and feasibility experience with the LVIS EVO stent., Materials and Methods: A multicenter, retrospective, observational study was conducted on patients who had intracranial aneurysms treated with the LVIS EVO stent across 3 Australian neurovascular centers between February 2020 and September 2020. Short-term technical and clinical outcomes were evaluated., Results: A total of 22 LVIS EVO stents were successfully implanted to treat 15 aneurysms (3 ruptured, 12 unruptured) in 15 patients. Aneurysms ranged from 2 mm to 35 mm in dome height. The LVIS EVO stent was used for stent-assisted coiling in 11 patients and flow diversion in 4 patients. There were no device-related procedural complications. There were 2 cases of peri-procedural symptomatic thromboembolic complications and no procedure-related mortality. At early radiological follow up, 10 patients had complete occlusion, 4 patients had small neck remnants, and 1 patient who was managed with flow diversion had a residual aneurysm., Conclusion: Early experience with the LVIS EVO stent demonstrated safety and feasibility for stent-assisted coiling as well as flow diversion for intracranial aneurysms. In this heterogeneous cohort, including ruptured, complex, and large aneurysms, all cases were technically successful.

To determine the variation in practices on meticillin-resistant Staphylococcus aureus (MRSA) surveillance and management of MRSA-colonized patients amongst 17 acute healthcare facilities in Singapore, the Ministry of Health convened a sharing session with Infection Prevention and Control Leads. All hospitals practised close to universal MRSA entry swabbing in keeping with national policy. There were, however, major variations in the response to both positive and negative surveillance swabs across facilities including the role of routine antiseptic bathing and MRSA decolonization. Most undertaking decolonization considered its role to be in 'bioburden reduction' rather than longer-term clearance., (Copyright © 2021. Published by Elsevier Ltd.)

Nodular glomerulosclerosis, typically diagnosed in patients with diabetes mellitus, has been reported in native kidneys of pre-diabetic patients but similar cases in kidney transplant recipients are lacking. We describe a case of nodular glomerulosclerosis in a kidney transplant recipient who had not been found to be diabetic despite regular screening and discuss the implications for the pathogenesis and diagnosis of nodular glomerulosclerosis and screening of post-transplant diabetes mellitus.

Objective: In this study, we trace the changes in the clinical and histological pattern of IgA nephritis (IgAN) in Singapore as it has evolved over 4 decades and compare the clinical, demographic, histological, and renal outcome of patients with IgAN from the 1 st decade and the 4 th decade., Materials and Methods: This is a retrospective study of all histologically proven IgAN diagnosed between 1976 and 2018. Clinical, laboratory, and histological characteristics between the 1 st and the 4 th decade, including treatment which could influence the disease progression and renal outcome of these two groups, were compared. We used the Oxford classification to compare the renal biopsy changes for these 2 decades as we were able to retrieve 125 renal biopsy tissues for the 1 st cohort of IgAN studied in the 1970s for the comparative study., Results: The commonest clinical presentation throughout the first 3 decades was asymptomatic hematuria and proteinuria (63, 52, and 49%, respectively). In the 4 th decade, nephrotic syndrome (31%) was the commonest followed by asymptomatic hematuria and proteinuria (30%), hypertension (21%), and chronic renal failure (11%). The data showed that treatment can modify the Oxford MEST - Crescent scores. Renin-angiotensin system (RAS) blockers modified the S scores, immunosuppressants modified the T and C scores, and combination therapy with RAS blockers and immunosuppressants modified the E, S, and T scores., Conclusion: The Oxford MEST classification offers a robust and expressive classification for early and late disease progression with respect to the development of end-stage renal disease (ESRD). E and S seem to be indices of continuing disease activity with progressive glomerulosclerosis, probably still amenable to therapy, but T was a predictive indicator for those destined for ESRD and no longer amenable to therapy.

Anemia is an important complication in patients with chronic kidney disease. Peritoneal dialysis (PD) is one of the most common modalities of kidney replacement therapy for patients with end-stage kidney disease. PD is particularly prevalent in the Asian Pacific region. Among the different countries and regions, including mainland China, Hong Kong, Japan, Malaysia, Singapore, South Korea, and Thailand, PD accounts for 2.8% to 74.6% of the dialysis population. In addition, 82% to 96% of the PD populations from these countries and regions are receiving erythropoiesis-stimulating agents (ESAs). Asian Pacific countries and regions follow the latest KDIGO (Kidney Disease: Improving Global Outcomes) guidelines for the initiation of treatment of anemia in PD patients. The types of ESAs commonly used include shorter-acting (epoetin alfa and beta) and longer-acting agents, including darbepoetin alfa or methoxy polyethylene glycol-epoetin beta. The most commonly used ESAs in Mainland China, Malaysia, Singapore, and Thailand are the shorter-acting agents, whereas in Hong Kong, Japan, and South Korea, longer-acting ESAs are most common. Oral iron therapy is still the most commonly used iron supplement. The route and dosage of iron administration in PD patients requires more research studies. With the introduction of oral hypoxia-inducible factor prolyl hydroxylase inhibitors into clinical use, the landscape of treatment of anemia in the PD population in the Asia Pacific region may change in the coming years., (© 2021 The Authors.)

Introduction: Social media provides opportunities for Interventional Radiologists to share research, communicate with colleagues, provide health information and advertise their clinical practice. This study aims to examine the online and social media presence of currently practicing Australian Interventional Radiologists., Methods: Systematic Google searches were undertaken in May 2019 and updated in May 2020 to identify practicing Interventional Radiologists in Australia. Comprehensive searches of practice websites and social media platforms (Facebook, LinkedIn, Twitter, ResearchGate, YouTube) were undertaken for each Interventional Radiologist., Results: There were 265 Interventional Radiologists identified as currently practising in Australia, including 209 Interventional Radiologists (excluding Interventional Neuroradiologists), 49 Interventional Neuroradiologists and 7 that practise across both Interventional Radiology and Interventional Neuroradiology. 72% of Interventional Radiologists had at least one social media account, with LinkedIn the most widely used social media platform (60%). There was a significant negative correlation between the total number of social media accounts and years in practice (P = 0.04). Across the states, a higher population per IR was positively correlated with a higher average number of social media accounts per IR (P = 0.04). Interventional Neuroradiologists had a significantly higher average number of social media accounts compared to Interventional Radiologists (1.94 vs 1.29, P < 0.01)., Conclusions: Most Australian Interventional Radiologists have a readily identifiable social media presence. There is potential for further utilisation of social media for academic, educational and business purposes., (© 2021 The Royal Australian and New Zealand College of Radiologists.)

This report describes a patient who presented with acute but transient right arm weakness and altered sensation secondary to severe stenosis of the left common carotid artery (CCA) origin. Endovascular stenting of the stenosed origin was achieved utilising a novel rendezvous technique through combined retrograde common carotid artery and anterograde transfemoral approaches. This technique has numerous potential advantages over traditional transfemoral endovascular and open retrograde common carotid artery approaches. It allows increased procedural control and success in traversing the stenosis and provides a smooth transition for the stent delivery catheter. An open cutdown procedure or open surgical technique is not required. Our patient recovered well from the procedure with no complications within the three-month follow up period.

Peritoneal dialysis (PD) requires patients to develop a variety of self-management skills in order to effectively deliver and manage their dialysis at home. eHealth interventions may provide patients with accessible information to develop the skills and knowledge they require to manage their treatment. This review aims to identify and evaluate 'active' eHealth interventions in supporting patients on PD. Six databases were included within the review using the terms Peritoneal Dialysis, eHealth, telemedicine and remote consultation . Studies which explored patients who were delivering PD, an intervention where the main component involved a digital device and required active engagement from patients were included. The primary outcomes examined were identified using the core outcomes recommended by the Standardised Outcomes in Nephrology in Peritoneal Dialysis initiative (PD infection, cardiovascular disease, mortality, PD failure and life participation). Hospitalisation rates were also considered as a primary outcome. Secondary outcomes included quality of life, patient skills, patient knowledge and satisfaction. Using the inclusion criteria, 15 studies (1334 participants) were included in the study. The effectiveness of eHealth interventions was mixed. Due to high heterogeneity, a meta-analysis was not possible, and quality of evidence was low. Risk of bias across the randomised studies was unclear but bias across non-randomised studies was identified as critical. There were no reported adverse effects of eHealth interventions within the included studies. Despite the high interest of eHealth interventions in PD, good quality evidence is needed to explore their effectiveness before a wider application of eHealth interventions.

Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.