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Background & Objective: Root canal infections are challenging to eradicate with conventional methods due to their complexity. Traditional chemical irrigants often fail to reach all bacterial colonies. Methylene blue (MB), used in photoactivated disinfection (PAD), generates reactive oxygen species (ROS) upon light activation, effectively killing bacteria. This study aimed to synthesize, characterize, and explore MB-functionalized reduced graphene oxide (MB/rGO) for enhanced photoactivated disinfection in root canal treatment., Methods: This in-vitro study was conducted from April 2024 to September 2024 at Universiti Sains Malaysia and King Faisal University. Graphene oxide (GO) was reduced by dispersing GO in deionized water with sonication, followed by adding sodium hydroxide (NaOH) under vigorous stirring. The suspension obtained was centrifuged, washed, and dried to yield reduced graphene oxide (rGO). For functionalization, rGO was dispersed in ethanol and mixed with methylene blue (MB) solution, followed by stirring and drying to obtain MB-functionalized rGO. The antibacterial and antifungal activities of MB alone and in combination with rGO, with or without laser exposure, were tested using the agar well diffusion method. The paired sample t-test was used to compare the inhibition zones for different treatment groups of E. faecalis and C. albicans ., Results: FTIR analysis confirmed successful functionalization by identifying specific functional groups of rGO and MB. Similarly, Raman spectroscopy indicated that GO-MB had an intermediate level of defects, and SEM analysis confirmed slight morphological changes with MB molecules attached to the rGO surface. Moreover, the antimicrobial test revealed that MB/rGO with laser performed significantly better ( p =0.042) than MB/rGO without laser and MB with laser group ( p =0.034) against E. faecalis ., Conclusions: The functionalization of MB with rGO and its application with laser treatment significantly enhanced antimicrobial and antifungal activity, suggesting potential benefits for endodontic treatments and other dental applications., Competing Interests: Conflicts of Interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

This study aimed to present a complete overview of the trends, difficulties, and improvements in dental treatment for children diagnosed with autism spectrum disorder through rigorous bibliometric analysis. The dimensional database field was chosen to enable the inclusion and recall of the greatest number of relevant entries. All peer-reviewed international journals published between 2004 and 2023 were included in this study. The sophisticated search keywords' Autistic Disorder" OR "Autism Spectrum Disorder" AND "Dental management" were used. Studies that examined patterns and difficulties in the dental care of children with ASD were included in the inclusion and exclusion criteria for this analysis. Among the listed countries, The United States had the highest number of documents and citations. Barbara Sheller is the most cited author, followed closely by Arthur H.Friedlander, Michael E.Mahler, and John A.Yagiela. This study also revealed that most articles involved multinational collaborations, highlighting the global scope of dental research. The United States leads in terms of research output and citations, followed by India and China. Research on autism spectrum disorder has grown substantially over the past few years, and the authors recommend that future research concentrate on creating effective behavioral techniques that will assist children with autism spectrum disorder in coping with dental treatment., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable due to the design of the study as a bibliometric analysis. Consent for publication: Not applicable. Informed consent: Not applicable due to the design of the study as a bibliometric analysis. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: This study aimed to identify and evaluate scholarly research on the efficacy, durability, and long-term stability of various adhesive systems used for bonding direct resin composite restorations and to identify factors influencing bonding performance, such as adhesive composition, application protocol, substrate type, and etching technique., Materials and Methods: An all-inclusive electronic database search for peer-reviewed scholarly journal articles was conducted using PubMed, ScienceDirect, Google Scholar, Dimensions, and the Cochrane Library for research articles investigating the effectiveness of different adhesive systems in direct resin composite restorations, excluding reviews, meta-analyses, opinion pieces, and case reports. The risk of bias was assessed using the Cochrane tool (Robvis 2.0). Data were extracted and thematically analyzed, and quantitative data were statistically analyzed using Review Manager software. Dichotomous data were evaluated using the Mantel-Haenszel method, applying a random effects model and 95% confidence interval., Results: The database search yielded 1632 potential articles, of which 14 were included in this study. Several adhesive systems exhibit excellent tensile bond strength. In addition, the type of resin composite, adhesive system, and artificial aging significantly influenced the bonding performance of resin composite restorations. However, the failure rates were low in the different adhesive systems, showing comparable results between the two-step etch-and-rinse and one-step self-etch adhesive systems (p = 0.71). The results showed an overall trend of high bonding effectiveness with a low incidence of adverse events, such as postoperative sensitivity, adhesive failure, and fractures., Conclusion: The study results emphasize the importance of selecting appropriate adhesive systems based on clinical case requirements, restoration characteristics, and patient factors to enhance bonding efficacy, durability, and long-term stability., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to British Dental Association.)

Objective: The main aim of this study was to identify the existing literature on the association between sporting activities and temporomandibular disorders and to critically appraise evidence of this association through a systematic review and meta-analysis., Design: A comprehensive search was conducted using PubMed, ScienceDirect, Dimensions, Google Scholar, Cochrane Library, and the Education Resources Information Centre (ERIC). Articles were selected using pre-specified eligibility criteria. In addition, the quality of eligible studies was assessed using the National Institutes of Health (NIH) for observational cohort and cross-sectional studies. Data were systematically extracted and analyzed., Results: Temporomandibular disorder symptoms, such as myofascial pain, clicking sounds, and musculoskeletal symptoms, were comparably prevalent among athletes and non-athletes, with some studies reporting contrasting results. However, meta-analyses of the comparisons demonstrated statistically insignificant differences between athletes and non-athletes. Additionally, there was a significant reduction in temporomandibular disorder symptoms when mouthguards were used., Conclusions: This comprehensive analysis of existing evidence highlights the various symptoms and clinical manifestations of TMD among athletes, including myofascial pain, clicking sounds, and musculoskeletal symptoms. This study established different prevalence rates in different sports., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Resin cement exhibits numerous therapeutic advantages over conventional luting materials. However, the effectiveness of the antibacterial properties of resin cement remains unclear. Nanotechnology provides a viable option, whereby the integration of nanoparticles (NPs) can potentially augment the antibacterial effectiveness of resin cement. The objective of this study was to conduct a comprehensive literature review to assess resin cement's antibacterial effectiveness by incorporating nanoparticles. An extensive search of PubMed and Scopus databases up to September 12, 2023, was conducted to identify relevant scholarly articles that examined and evaluated resin cement's antibacterial effectiveness with and without the incorporation of nanoparticles (NPs). This systematic review adhered to the PRISMA guidelines for reporting the results. The search retrieved seven eligible studies. Studies indicated that resin cement with NPs significantly reduced the colony forming unit (CFU) counts compared to resin cement without NPs. Furthermore, resin cement, in addition to NPs, significantly reduced the bacterial metabolic activity compared to the control group. The use of nanoparticles (NPs) in resin cement has been shown to enhance its antibacterial properties, possibly mitigating the occurrence of secondary caries. Future clinical trials are required to validate the beneficial effects of NPs in conjunction with resin cement in the prevention of secondary caries., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: Not applicable. Consent for publication: Not applicable. Conflict of interest: The authors declare no conflict of interest., (© 2024. The Author(s).)

Purpose: Virtual reality (VR) simulations have been increasingly employed to train dental students prior to clinical practice. According to the literature, blended learning designs in the form of VR simulations can be utilized by both dental students and instructors to provide quality education. They can also save time and improve motor skills before students enter clinical stages. Therefore, this study was designed to review the importance of available VR simulators and their impact on student learning and outcomes., Method: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed to review the literature systematically, and different databases such as PubMed, ScienceDirect, Cochrane Library, Scopus, and Google Scholar were searched (up to December 2023) for relevant articles using keywords: "virtual reality," "virtual reality simulators," "virtual reality simulation," and "dental education." The Mixed Methods Appraisal Tool was used to assess the study quality., Results: After a comprehensive literature search, 1477 research articles were identified, of which 16 were included in the present study. In terms of students' learning outcomes, engagement, and optimal approach, a significant improvement was observed compared to conventional training methods, specifically in their knowledge, performance, confidence, and psychomotor skills., Conclusion: The findings suggest that VR simulators enhance the overall learning abilities of dental students and should be regarded as an integral component of the current curriculum. However, it is important to recognize that VR simulators cannot fully substitute traditional training methods; rather, they can effectively complement them., (© 2024 American Dental Education Association.)

Objective: Acinetobacter baumannii, one of the ESKAPE pathogens, is on the World Health Organization (WHO) list of priorities needing urgent new effective antimicrobial agents due to exhibited high resistance by the bacterium to currently available antibiotics. This study examines the periodic changes of clinical A. baumannii isolates and their antimicrobial resistance patterns and types in Southeastern region of Saudi Arabia., Materials and Methods: One hundred and seventy-seven randomly selected A. baumannii isolates were used for the investigation with bacterial identities (IDs) and antimicrobial assay ascertained with Gram-negative (GN) ID cards and antimicrobial susceptibility test (AST) cards of Vitek 2 Compact Automated System according to manufacturer's guidelines. Descriptive phenotypic types of isolates were compared using comparison proportion and Fisher extraction test, while Morpheus versatile matrix visualization and analysis software was used for the dendrogram of hierarchical clustering., Results: A significantly higher proportion of samples were from males compared to females (p = 0.025), with 33.33% of samples originating from patients aged 51-70 years. Resistance was high for imipenem (93%), meropenem (94%), levofloxacin, ciprofloxacin (99%), and aztreonam (98%). There was less percentage resistance to colistin (18%), tigecycline (23%), and minocycline (23%). Multidrug resistance (MDR)/carbapenem-resistant Acinetobacter baumannii (CRAB) was observed consistently across all years. There was no extensive drug resistance (XDR) among isolates from 2013 to 2014, but it was present in the 2016 to 2018 and 2019 to 2020 periods, while pandrug resistance was seen only in the 2019 to 2020 isolates., Conclusions: The study shows a clear trend of the isolates changing from MDR to XDR and then to pandrug resistance over the study period. Also, it indicates that carbapenems might no longer be a treatment choice in this study region. Although colistin exhibited less resistance, the toxicity of the drug reduces its usefulness. The development of pandrug resistance is a critical concern.

Objective: This study aimed to provide valuable insights into the current research status and gaps in digital intraoral scanner literature in dentistry., Methodology: Scopus Search Query TITLE-ABS-KEY (intraoral AND scanners AND (dentistry OR digital AND dentistry)). The search query used in Scopus for the bibliometric analysis was "TITLE-ABS-KEY (intraoral AND scanners AND (dentistry OR digital AND dentistry))." This query indicates that the analysis focused on documents in which the title, abstract, or keywords contained the terms "intraoral," "scanners," and either "dentistry" or "digital dentistry.", Results: The analysis covers a timespan from 1998 to 2023 and includes 331 documents sourced from 136 publications. The annual growth rate of research in this field is reported to be 15.9%, indicating a steady increase over time. Among the top sources, the "Journal of Esthetic and Restorative Dentistry" and the "Journal of Prosthetic Dentistry" have the highest number of articles, indicating their significance in the field. Some notable authors and their corresponding statistics include WÖSTMANN B, with 15 articles and a fractionalized value of 3.16, and SCHLENZ MA, with 14 articles and a fractionalized value of 2.91. The United States has the highest number of articles, indicating a significant presence in research publications. Germany closely follows this, demonstrating a notable contribution to the scientific community., Conclusions: This bibliometric analysis of intraoral scanners used in dentistry provided valuable insights into the current state of research and scholarly publications in this field. This analysis sheds light on the trends, patterns, and advancements in the use of these scanners in dental practice., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Nanoparticles are increasingly used in dentistry for various applications, including enhancing the mechanical properties of denture base resins. This study aimed to comprehensively review and analyze the research landscape of nanoparticles and their effect on the flexural strength of denture base resins to identify key research areas and trends and to highlight the importance of collaboration between authors and institutions., Methods: A Bibliometric Analysis was conducted using the Keywords "Nanoparticle*" AND "Denture*" OR "CAD/CAM." The literature search from the WOS database was restricted to the publication years 2011 to 2022., Results: Key findings encompass an increase in research publications but a decline in citations. Saudi Arabia, China, and Iraq led this research, with specific institutions excelling. Notable journals with high impact factors were identified. Authorship patterns show variations in citation impact. Additionally, keyword analysis revealed that current research trends offer insights into influential authors and their networks., Conclusions: The analysis of nanoparticles and denture base resins reveals a dynamic and evolving landscape that emphasizes the importance of collaboration, staying current with research trends, and conducting high-quality research in this ever-evolving domain., (© 2024. The Author(s).)

Aim: The integration of advanced technologies, including three-dimensional (3D) imaging modalities and virtual simulations, has significantly influenced contemporary approaches to preoperative planning in implant dentistry. Through a meticulous analysis of relevant studies, this review synthesizes findings related to accuracy outcomes in implant placement facilitated by 3D imaging in virtual patients., Methods: A comprehensive literature search was conducted across relevant databases to identify relevant studies published to date. The inclusion criteria were studies utilizing 3D imaging techniques, virtual patients, and those focusing on the accuracy of dental implant planning and surgical placement. The selected studies were critically appraised for their methodological quality., Results: After a rigorous analysis, 21 relevant articles were included out of 3021 articles. This study demonstrates the versatility and applicability of these technologies in both in vitro and in vivo settings. Integrating Computer-Aided Design/Computer-Aided Manufacturing (CAD/CAM), cone bean computed tomography (CBCT), and advanced 3D reconstruction methodologies showcases a trend toward enhanced precision in implant planning and placement. Notably, the evaluation parameters varied, encompassing distances, discrepancies, and deviations in the implant placement. The ongoing integration of systems such as dynamic navigation systems, augmented reality, and sophisticated software platforms shows a promising trajectory for the continued refinement of virtual reality applications in dental implantology, providing valuable insights for future research and clinical implementation. Moreover, using stereolithographic surgical guides, virtual planning with CBCT data, and 3D-printed templates consistently demonstrates enhanced precision in dental implant placement compared to traditional methods., Conclusion: The synthesis of the available evidence underscores the substantial positive impact of 3D imaging techniques and virtual patients on dental implant planning and surgical placement accuracy. Utilizing these technologies contributes to a more personalized and precise approach that enhances overall treatment outcomes. Future research directions and potential refinements to the application of these technologies in clinical practice should be discussed., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objective: The current body of research on utilizing botulinum toxin (BTX) to manage temporomandibular disorders (TMDs) has not yet yielded definitive conclusions. The primary objective of this study was to determine the effectiveness of BTX in pain reduction for TMDs compared to placebo and other treatments. The secondary outcomes evaluated were adverse events, maximum mouth opening, bruxism events, and maximum occlusal force., Materials and Methods: A literature search was performed on PubMed, Dimension Publication, Scopus, and Google Scholar. The RoB 2 tool was used for quality assessment. The mean differences in pain scores were estimated to measure the effect of BTX on pain reduction. For adverse events, the risk ratio for the incidence of side effects was calculated., Results: Two hundred and sixty non-duplicate articles were identified; however, only 14 RCTS were included in this review. The total study population included 395 patients. The overall risk of bias showed a low to moderate quality of evidence. Results from 6 studies were reported only narratively; four studies were used for meta-analysis on pain reduction, and five were used for meta-analysis on adverse events. The control used in the meta-analysis was placebo injections. Results of the meta-analysis for pain reduction were statistically insignificant for the BTX group with mean differences at MD = -1.71 (95% CI, -2.87 to -0.5) at one month, -1.53 (95% CI, -2.80 to -0.27) at three months, and -1.33 (95% CI, -2.74 to 0.77) at six months. This showed that BTX treatment was not significantly better than placebo for a reduction in pain scores at 1, 3, and 6 months. Regarding safety, the placebo group showed a relative risk of 1.34 (95%CI, 0.48-6.78) and 1.17 (95%CI, 0.54-3.88) at 1 and 3 months respectively. However, the risks were not statistically significant. There was also no difference in the effectiveness of BTX compared to placebo and other treatments for maximum mouth opening, bruxism events, and maximum occlusal force., Conclusion: BTX was not associated with better outcomes in terms of pain reduction, adverse events, maximum mouth opening, bruxism events, and maximum occlusal force. More high-quality RCTs are needed to better understand this topic., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Saini 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.)

Background: Three-dimensional (3D) printing technology has revolutionized dentistry, particularly in fabricating provisional restorations. This systematic review and meta-analysis aimed to thoroughly evaluate the flexural strength of provisional restorations produced using 3D printing while considering the impact of different resin materials., Methods: A systematic search was conducted across major databases (ScienceDirect, PubMed, Web of Sciences, Google Scholar, and Scopus) to identify relevant studies published to date. The inclusion criteria included studies evaluating the flexural strength of 3D-printed provisional restorations using different resins. Data extraction and quality assessment were performed using the CONSORT scale, and a meta-analysis was conducted using RevMan 5.4 to pool results., Results: Of the 1914 initially identified research articles, only 13, published between January 2016 and November 2023, were included after screening. Notably, Digital Light Processing (DLP) has emerged as the predominant 3D printing technique, while stereolithography (SLA), Fused Deposition Modeling (FDM), and mono-liquid crystal displays (LCD) have also been recognized. Various printed resins have been utilized in different techniques, including acrylic, composite resins, and methacrylate oligomer-based materials. Regarding flexural strength, polymerization played a pivotal role for resins used in 3D or conventional/milled resins, revealing significant variations in the study. For instance, SLA-3D and DLP Acrylate photopolymers displayed distinct strengths, along with DLP bisacrylic, milled PMMA, and conventional PMMA. The subsequent meta-analysis indicated a significant difference in flexure strength, with a pooled Mean Difference (MD) of - 1.25 (95% CI - 16.98 - 14.47; P < 0.00001) and a high I 2 value of 99%, highlighting substantial heterogeneity among the studies., Conclusions: This study provides a comprehensive overview of the flexural strength of 3D-printed provisional restorations fabricated using different resins. However, further research is recommended to explore additional factors influencing flexural strength and refine the recommendations for enhancing the performance of 3D-printed provisional restorations in clinical applications., (© 2023. The Author(s).)

Background: Sleep bruxism is a prevalent condition in dentistry practice, characterized by involuntary grinding or clenching of the teeth during sleep. Several therapies, including occlusal splints, have been used to manage sleep bruxism and temporomandibular disorders, including occlusal splints. This study aimed to compare the effectiveness of different occlusal splints in managing sleep bruxism., Methods: The PICO framework encompasses the characterization of the population, intervention, comparison, and pertinent outcomes. A comprehensive and systematic literature review was conducted on PubMed, Scopus, and Google Scholar to identify grey literature. The search specifically targeted scientific studies published before September 20, 2023. The Cochrane Collaboration Risk of Bias Tool assessed the accuracy of the included Randomized Control Trials (RCTs). The modified Newcastle-Ottawa Scale assessed non-randomized studies. Data were systematically extracted, synthesized, and reported thematically., Results: Out of the total of 808 articles that were evaluated, only 15 articles were found to meet the specified inclusion criteria. Adjustable splints, such as full-occlusion biofeedback splints, were more effective in reducing sleep bruxism episodes, improving patient-reported symptoms, and enhancing overall well-being. The impact of different occlusal sprints on electromyographic activity varies, and potential adverse effects should be considered individually., Conclusions: This review provides valuable insights into the effectiveness of occlusal splints in managing sleep bruxism. The results of this study indicate that occlusal splint therapy is a viable treatment approach for sleep bruxism., (© 2023. The Author(s).)

Objective: Appliance biocompatibility, orthodontic treatment efficiency and patient convenience are the major issues confronting contemporary orthodontic practice. Very few studies have been published till date regarding the efficiency of self-ligating brackets as against conventional brackets. Hence, the present study was planned to compare the rate of canine retraction between self-ligating and conventional brackets and to determine the amount of anchorage loss during canine retraction., Methods: The present clinical study was designed as a prospective, observational study comprising of 25 patients requiring first premolar extraction as a part of orthodontic treatment. Self-ligating and conventional brackets were bonded using a split-mouth study design randomly. Retraction of canines was done with 150 grams of force using Dontrix gauge with E-chains. The study was conducted in relation to upper arch only, while the rate of retraction was evaluated every 4 weeks for 3 months. Average rates of retraction in 3 months were calculated. For anchorage loss, an acrylic guide plug was used in mid-treatment cast (T0) and after 3 months of retraction (T3). The statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 17.0 (SPSS Inc., Chicago, IL, USA). Independent t-test was used to compare the means of the two variables studied, while Pearson's correlation coefficient was used to evaluate the correlation between the variables studied in the groups included. P < .05 was considered statistically significant., Results: The correlation coefficient between the average rate of canine retraction with self-ligating brackets vs. conventional brackets over a period of 3 months came out to be 0.6434, while on comparing the data in terms of anchorage loss over a period of 3 months, the respective correlation coefficient value was found to be 0.6659 with the results being statistically highly significant in either case ( P < .001)., Conclusions: Self-ligating brackets showed double the amount of displacement compared to conventional brackets in some of the cases. Also, chair side time was significantly reduced with self-ligating brackets as against conventional brackets., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Orthodontic Science.)

Extensive drug resistance to bacterial infections in hospitalised patients is accompanied by high morbidity and mortality rates due to limited treatment options. This study investigated the clinical outcomes of single and combined antibiotic therapies in extensive (XDR), multidrug-resistant (MDR) and susceptible strains (SS) of hospital-acquired infections (HAIs). Cases of hospital-associated drug-resistant infections (HADRIs) and a few susceptible strains from hospital wards were selected for this study. Bacteria identifications (IDs) and antimicrobial susceptibility tests (ASTs) were performed with a Vitek 2 Compact Automated System. Patients' treatment types and clinical outcomes were classified as alive improved (AI), alive not improved (ANI), or died. The length of hospital stay (LOHS) was acquired from hospital records. The HAI pathogens were Acinetobacter baumannii (28%), Escherichia coli (26%), Klebsiella pneumoniae (22%), Klebsiella (2%) species, Pseudomonas aeruginosa (12%), Proteus mirabilis (4%), and other Enterobacteriaceae . They were MDR (40.59%), XDR (24.75%), carbapenem-resistant Enterobacteriaceae (CRE, 21.78%) and susceptible (12%) strains. The treatments were either monotherapy or combined therapy with different outcomes. Monotherapy produced positive significant outcomes with E. coli infections, while for P. aeruginosa, there were no differences between the number of infections treated with either mono/combined therapies (50% each). Nonetheless, combined therapy had significant effects ( p < 0.05) as a treatment for A. baumannii and K. pneumoniae infections. Clinical outcomes and LOHS varied with infecting bacteria. The prevalence of XDR and MDR HAIs was found to be significantly high, with no association with treatment type, LOHS, or outcome.

Intensive care units (ICUs) may disrupt sleep. Quantitative ICU studies of concurrent and continuous sound and light levels and timings remain sparse in part due to the lack of ICU equipment that monitors sound and light. Here, we describe sound and light levels across three adult ICUs in a large urban United States tertiary care hospital using a novel sensor. The novel sound and light sensor is composed of a Gravity Sound Level Meter for sound level measurements and an Adafruit TSL2561 digital luminosity sensor for light levels. Sound and light levels were continuously monitored in the room of 136 patients (mean age = 67.0 (8.7) years, 44.9% female) enrolled in the Investigation of Sleep in the Intensive Care Unit study (ICU-SLEEP; Clinicaltrials.gov: #NCT03355053), at the Massachusetts General Hospital. The hours of available sound and light data ranged from 24.0 to 72.2 hours. Average sound and light levels oscillated throughout the day and night. On average, the loudest hour was 17:00 and the quietest hour was 02:00. Average light levels were brightest at 09:00 and dimmest at 04:00. For all participants, average nightly sound levels exceeded the WHO guideline of < 35 decibels. Similarly, mean nightly light levels varied across participants (minimum: 1.00 lux, maximum: 577.05 lux). Sound and light events were more frequent between 08:00 and 20:00 than between 20:00 and 08:00 and were largely similar on weekdays and weekend days. Peaks in distinct alarm frequencies (Alarm 1) occurred at 01:00, 06:00, and at 20:00. Alarms at other frequencies (Alarm 2) were relatively consistent throughout the day and night, with a small peak at 20:00. In conclusion, we present a sound and light data collection method and results from a cohort of critically ill patients, demonstrating excess sound and light levels across multiple ICUs in a large tertiary care hospital in the United States. ClinicalTrials.gov, #NCT03355053. Registered 28 November 2017, https://clinicaltrials.gov/ct2/show/NCT03355053.

Purpose: Sleep-disordered breathing may be induced by, exacerbate, or complicate recovery from critical illness. Disordered breathing during sleep, which itself is often fragmented, can go unrecognized in the intensive care unit (ICU). The objective of this study was to investigate the prevalence, severity, and risk factors of sleep-disordered breathing in ICU patients using a single respiratory belt and oxygen saturation signals., Methods: Patients in three ICUs at Massachusetts General Hospital wore a thoracic respiratory effort belt as part of a clinical trial for up to 7 days and nights. Using a previously developed machine learning algorithm, we processed respiratory and oximetry signals to measure the 3% apnea-hypopnea index (AHI) and estimate AH-specific hypoxic burden and periodic breathing. We trained models to predict AHI categories for 12-h segments from risk factors, including admission variables and bio-signals data, available at the start of these segments., Results: Of 129 patients, 68% had an AHI ≥ 5; 40% an AHI > 15, and 19% had an AHI > 30 while critically ill. Median [interquartile range] hypoxic burden was 2.8 [0.5, 9.8] at night and 4.2 [1.0, 13.7] %min/h during the day. Of patients with AHI ≥ 5, 26% had periodic breathing. Performance of predicting AHI-categories from risk factors was poor., Conclusions: Sleep-disordered breathing and sleep apnea events while in the ICU are common and are associated with substantial burden of hypoxia and periodic breathing. Detection is feasible using limited bio-signals, such as respiratory effort and SpO 2 signals, while risk factors were insufficient to predict AHI severity., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Basilar artery occlusion (BAO) is associated with high morbidity and mortality. Endovascular therapy (EVT) has been shown to be beneficial in acute BAO patients. This retrospective observational study used the National Inpatient Sample (NIS) database to identify BAO patients using the International Classification of Diseases (ICD). Multivariable models were used to evaluate the association of risk factors, comorbidities, length of stay (LOS) in hospital, total cost, disposition, and transfer status. A total of 1120 (447 females, 39.95%) patients were identified, with a higher proportion of White individuals (66.8% vs. 57.6%), atrial fibrillation (31.5% vs. 17.2%; p < 0.0001), and peripheral vascular disease (21.2% vs. 13.7%; p = 0.009). A lower proportion of individuals with diabetes mellitus (32.1% vs. 39.5%; p = 0.05) was found in the EVT group. Majority of the patients (924/1120, 82.5%) were treated at the urban teaching facility, which also performed most of the EVT procedures (164, 89.13%), followed by non-academic urban (166, 14.8%) and rural (30, 2.7%) hospitals. Most patients (19/30, 63%) admitted to rural hospitals were transferred to other facilities. Urban academic hospitals also had the highest median LOS (8.9 days), cost of hospitalization (USD 117,261), and disposition to home (32.6%). This study observed distinct patterns and geographical disparities in the acute treatment of BAO patients. There is a need for national- and state-level strategies to improve access to stroke care.

Neurologic disability level at hospital discharge is an important outcome in many clinical research studies. Outside of clinical trials, neurologic outcomes must typically be extracted by labor intensive manual review of clinical notes in the electronic health record (EHR). To overcome this challenge, we set out to develop a natural language processing (NLP) approach that automatically reads clinical notes to determine neurologic outcomes, to make it possible to conduct larger scale neurologic outcomes studies. We obtained 7314 notes from 3632 patients hospitalized at two large Boston hospitals between January 2012 and June 2020, including discharge summaries (3485), occupational therapy (1472) and physical therapy (2357) notes. Fourteen clinical experts reviewed notes to assign scores on the Glasgow Outcome Scale (GOS) with 4 classes, namely 'good recovery', 'moderate disability', 'severe disability', and 'death' and on the Modified Rankin Scale (mRS), with 7 classes, namely 'no symptoms', 'no significant disability', 'slight disability', 'moderate disability', 'moderately severe disability', 'severe disability', and 'death'. For 428 patients' notes, 2 experts scored the cases generating interrater reliability estimates for GOS and mRS. After preprocessing and extracting features from the notes, we trained a multiclass logistic regression model using LASSO regularization and 5-fold cross validation for hyperparameter tuning. The model performed well on the test set, achieving a micro average area under the receiver operating characteristic and F-score of 0.94 (95% CI 0.93-0.95) and 0.77 (0.75-0.80) for GOS, and 0.90 (0.89-0.91) and 0.59 (0.57-0.62) for mRS, respectively. Our work demonstrates that an NLP algorithm can accurately assign neurologic outcomes based on free text clinical notes. This algorithm increases the scale of research on neurological outcomes that is possible with EHR data., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Introduction: To measure sleep in the intensive care unit (ICU), full polysomnography is impractical, while activity monitoring and subjective assessments are severely confounded. However, sleep is an intensely networked state, and reflected in numerous signals. Here, we explore the feasibility of estimating conventional sleep indices in the ICU with heart rate variability (HRV) and respiration signals using artificial intelligence methods Methods: We used deep learning models to stage sleep with HRV (through electrocardiogram) and respiratory effort (through a wearable belt) signals in critically ill adult patients admitted to surgical and medical ICUs, and in age and sex-matched sleep laboratory patients Results: We studied 102 adult patients in the ICU across multiple days and nights, and 220 patients in a clinical sleep laboratory. We found that sleep stages predicted by HRV- and breathing-based models showed agreement in 60% of the ICU data and in 81% of the sleep laboratory data. In the ICU, deep NREM (N2 + N3) proportion of total sleep duration was reduced (ICU 39%, sleep laboratory 57%, p < 0.01), REM proportion showed heavy-tailed distribution, and the number of wake transitions per hour of sleep (median 3.6) was comparable to sleep laboratory patients with sleep-disordered breathing (median 3.9). Sleep in the ICU was also fragmented, with 38% of sleep occurring during daytime hours. Finally, patients in the ICU showed faster and less variable breathing patterns compared to sleep laboratory patients Conclusion: The cardiovascular and respiratory networks encode sleep state information, which, together with artificial intelligence methods, can be utilized to measure sleep state in the ICU., Competing Interests: Author DK is employed by MyAir Inc. The remaining 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. The funder ‘MyAir Inc’ had the following involvement with the study: Supply of breathing belts (“Airgo”), data acquisition software, and participation of initial qualitative breathing data analysis. The funder was not involved in the interpretation of data, the writing of this article or the decision to submit it for publication., (Copyright © 2023 Ganglberger, Krishnamurthy, Quadri, Tesh, Bucklin, Adra, Da Silva Cardoso, Leone, Hemmige, Rajan, Panneerselvam, Paixao, Higgins, Ayub, Shao, Coughlin, Sun, Ye, Cash, Thompson, Akeju, Kuller, Thomas and Westover.)

The present study aimed to identify the effects of sugar and methods (slow freezing [SF] vs. fast freezing [FF]) on post-thaw in vitro functional characteristics of cryopreserved caprine spermatogonial stem cells (cSSCs) and the cells obtained from cryopreserved testis tissue of prepubertal Barbari bucks. For this, in experiment 1, cSSCs were isolated and cryopreserved by either SF or FF method with different non-permeable (sugars; trehalose [140 mm; 140T or 400 mm; 400T] and sucrose [140 mm; 140S or 400 mm; 400S]) or/and permeable (5% ethylene glycol [EG] and dimethyl sulfoxide) cryoprotectants. After 1 week of cryopreservation, the cSSCs were thawed and cultured for evaluation of their characteristics. Further, in experiment 2, the effectiveness of sugars (trehalose [140 mm] or sucrose [140 mm]) for cryopreservation of testicular tissues of prepubertal Barbari bucks using the SF or FF method was evaluated. After 1 week of cryopreservation, the tissues were thawed and cSSCs were isolated and cultured for 3 weeks. In both experiments, cSSCs were evaluated for recovery rate, proliferation, metabolic viability, senescence, and stemness markers' expression. The recovery rate was 1.3-, 1.3-, and 1.1-fold higher in the 140T group compared with EG, 140S, and 400S groups, respectively. Similarly, the expression of stemness markers (protein gene product 9.5 and octamer-binding transcription factor-4) was relatively higher in 140T group compared with the other groups. In experiment 2, the recovery rate of cells per unit tissue weight was significantly (p &lt; 0.05) higher when cryopreserved using 140 mm trehalose compared with other groups. The results of immunocytochemical analyses imply the expression of pluripotent stem cell markers in cSSCs following cryopreservation. Overall, the outcome of the study demonstrates different effects of sugars and methods on post-thaw functional properties of cSSCs with superiority of 140 mm trehalose using SF method over other treatment groups. These results are important for ex vivo expansion and differentiation of cSSCs for fertility preservation and their other downstream applications., (© 2023 S. Karger AG, Basel.)

Inflammation-mediated alterations in glutamate neurotransmission constitute the most important pathway in the pathophysiology of various brain disorders. The excessive signalling of glutamate results in excitotoxicity, neuronal degeneration, and neuronal cell death. In the present study, we investigated the relative efficacy of black cumin ( Nigella sativa ) oil with high (5 % w/w) and low (2 % w/w) thymoquinone content (BCO-5 and BCO-2, respectively) in alleviating ibotenic acid-induced excitotoxicity and neuroinflammation in Wistar rats. It was found that BCO-5 reversed the abnormal behavioural patterns and the key inflammatory mediators (TNF-α and NF-κB) when treated at 5 mg/kg body weight. Immunohistochemical studies showed the potential of BCO-5 to attenuate the glutamate receptor subunits NMDA and GluR-2 along with increased glutamate decarboxylase levels in the brain tissues. Histopathological studies revealed the neuroprotection of BCO-5 against the inflammatory lesions, as evidenced by the normal cerebellum, astrocytes, and glial cells. BCO-2 on the other hand showed either a poor protective effect or no effect even at a 4-fold higher concentration of 20 mg/kg body weight indicating a very significant role of thymoquinone content on the neuroprotective effect of black cumin oil and its plausible clinical efficacy in counteracting the anxiety and stress-related neurological disorders under conditions such as depression and Alzheimer's disease., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a clinical and neuropsychiatric syndrome that can occur days to weeks following administration chimeric antigen receptor (CAR) T-cell therapy. Manifestations of ICANS range from encephalopathy and aphasia to cerebral edema and death. Because the onset and time course of ICANS is currently unpredictable, prolonged hospitalization for close monitoring following CAR T-cell infusion is a frequent standard of care., Methods: This study was conducted at Brigham and Women's Hospital from April 2015 to February 2020. A cohort of 199 hospitalized patients treated with CAR T-cell therapy was used to develop a combined hidden Markov model and lasso-penalized logistic regression model to forecast the course of ICANS. Model development was done using leave-one-patient-out cross validation., Results: Among the 199 patients included in the analysis 133 were male (66.8%), and the mean (SD) age was 59.5 (11.8) years. 97 patients (48.7%) developed ICANS, of which 59 (29.6%) experienced severe grades 3-4 ICANS. Median time of ICANS onset was day 9. Selected clinical predictors included maximum daily temperature, C reactive protein, IL-6, and procalcitonin. The model correctly predicted which patients developed ICANS and severe ICANS, respectively, with area under the curve of 96.7% and 93.2% when predicting 5 days ahead, and area under the curve of 93.2% and 80.6% when predicting the entire future risk trajectory looking forward from day 5. Forecasting performance was also evaluated over time horizons ranging from 1 to 7 days, using metrics of forecast bias, mean absolute deviation, and weighted average percentage error., Conclusion: The forecasting model accurately predicts risk of ICANS following CAR T-cell infusion and the time course ICANS follows once it has begun.Cite Now., Competing Interests: Competing interests: MBW and SSC are co-founders of Beacon Biosignals, which played no role in this work. DBR served on the scientific advisory board for Celgene/Bristol Meyers Squib. JD received research support from Novartis, consulting fees from Amgen, Blue Earth Diagnostics, and Syndax and royalties from contributing to UpToDate. CAJ received consulting fees from Kite/Gilead, Novartis, BMS/Celgene, Bluebird Bio, Epizyme, Instill-Bio, Lonza, Ipsen, Abintus-Bio, Daiichi-Sankyo and research funding from Kite/Gilead and Pfizer. Other authors report no disclosures relevant to the manuscript., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The busulfan, an alkylating agent, suppresses endogenous spermatogenesis in recipient testes. However, considering a wide variation in the effects of busulfan among animal species, its dosage and route of infusion need optimization to prepare effective and safe recipients. Thus, the current study aimed to create a suitable recipient goat model for germ cell (Gc) transplantation through a single intra-testicular (i.t.) busulfan infusion under ultrasonographic (USG) guidance. As observed through the infusion of trypan blue under USG guidance into mediastinum testis (MT) of pre-pubertal Barbari bucks, 3-5 mL of trypan blue solution could fill almost 80% of seminiferous tubules. Thereafter, in Experiment-1, the effect of different busulfan doses (mg/kg) i.e. 0 [negative control, Group (Gr) 1; 0 mg/kg-MT], 1 (Gr 2; 1 mg/kg-MT), 2 (Gr 3; 2 mg/kg-MT), and 3 (Gr 4; 3 mg/kg-MT) were studied. Further, in Experiment-2, sterilizing effects of busulfan infusion through two different routes [MT or cavum vaginale (CV)] were compared. Following i.t. busulfan treatment, no adverse physiological effects or body weight loss were detected. The histological analyses demonstrate a dose-dependent depletion of Gc with almost complete loss of Gc and spermatogenic activities in Gr 3 and 4, and extensive fibrosis in Gr 4. A considerable suppression of spermatogenesis marked with devoid of endogenous spermatogonial population and absence of significant (P > 0.05) effect on key hematological variables were observed in 2 mg/kg-MT Gr. These findings coupled with the results of significant (P < 0.05) down-regulation of marker genes of undifferentiated spermatogonia (THY-1 and PLZF), Gc pluripotency (UCHL-1, OCT-4, and DDX-4), and adhesion (E-cadherin and β-integrin); up-regulation of apoptotic genes (ID - 4 and BCL-6), and unchanged expression of Sertoli cell marker (vimentin), confirmed the safe and efficient depletion of endogenous Gc in 2 mg/kg-MT Gr. Furthermore, the effect of busulfan infusion on scrotal-testicular biometry, endocrine variables (plasma cortisol and testosterone), and Gc removal was more evident when busulfan was infused into MT than into CV. Overall, the results demonstrated that 2.0 mg/kg is an optimal single dose of busulfan when infused into the MT under USG guidance for the preparation of pre-pubertal recipient bucks. Overall, this study provides a basis to prepare suitable recipients through providing an available niche for efficient Gc transplantation in goats., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Quantifying and optimizing the polyphenol content of  Phyllanthus maderaspatensis  was accomplished using a single-solvent HPTLC system. Analyzing hydroalcoholic extracts for kaempferol, rutin, ellagic acid, quercetin, catechin, and gallic acid, we simultaneously quantified and optimized their concentration. In the experiment, the methanol to water ratio (%), temperature (°C), and time of extraction (min) were all optimized using a Box-Behnken statistical design. Kaempferol, rutin, ellagic acid, quercetin, catechin, and gallic acid were among the dependent variables analyzed. In the HPTLC separation, silica gel 60F254 plates were used, and toluene, ethyl acetate, and formic acid (5:4:1) made up the mobile phase. For kaempferol, rutin, ellagic acid, quercetin, catechin, and gallic acid, densitometric measurements were carried out using the absorbance mode at 254 nm. Hydroalcoholic extract of  P. maderaspatensis  contains rutin (0.344), catechin (2.62), gallic acid (0.93), ellagic acid (0.172), quercetin (0.0108) and kaempferol (0.06). Further, it may be affected by more than one factor at a time, resulting in a varying degree of reaction. A negative correlation was found between X1 (extraction time (min)) and X2 (temperature), as well as X1 and X3 (solvent ratios). Taking these characteristics into consideration, the method outlined here is a validated HPTLC method for measuring kaempferol, rutin, ellagic acid, quercetin, catechin, and gallic acid., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

To develop a physiologic grading system for the severity of acute encephalopathy manifesting as delirium or coma, based on EEG, and to investigate its association with clinical outcomes., Design: This prospective, single-center, observational cohort study was conducted from August 2015 to December 2016 and October 2018 to December 2019., Setting: Academic medical center, all inpatient wards., Patients/subjects: Adult inpatients undergoing a clinical EEG recording; excluded if deaf, severely aphasic, developmentally delayed, non-English speaking (if noncomatose), or if goals of care focused primarily on comfort measures. Four-hundred six subjects were assessed; two were excluded due to technical EEG difficulties., Interventions: None., Measurements and Main Results: A machine learning model, with visually coded EEG features as inputs, was developed to produce scores that correlate with behavioral assessments of delirium severity (Confusion Assessment Method-Severity [CAM-S] Long Form [LF] scores) or coma; evaluated using Spearman R correlation; area under the receiver operating characteristic curve (AUC); and calibration curves. Associations of Visual EEG Confusion Assessment Method Severity (VE-CAM-S) were measured for three outcomes: functional status at discharge (via Glasgow Outcome Score [GOS]), inhospital mortality, and 3-month mortality. Four-hundred four subjects were analyzed (mean [sd] age, 59.8 yr [17.6 yr]; 232 [57%] male; 320 [79%] White; 339 [84%] non-Hispanic); 132 (33%) without delirium or coma, 143 (35%) with delirium, and 129 (32%) with coma. VE-CAM-S scores correlated strongly with CAM-S scores (Spearman correlation 0.67 [0.62-0.73]; p < 0.001) and showed excellent discrimination between levels of delirium (CAM-S LF = 0 vs ≥ 4, AUC 0.85 [0.78-0.92], calibration slope of 1.04 [0.87-1.19] for CAM-S LF ≤ 4 vs ≥ 5). VE-CAM-S scores were strongly associated with important clinical outcomes including inhospital mortality (AUC 0.79 [0.72-0.84]), 3-month mortality (AUC 0.78 [0.71-0.83]), and GOS at discharge (0.76 [0.69-0.82])., Conclusions: VE-CAM-S is a physiologic grading scale for the severity of symptoms in the setting of delirium and coma, based on visually assessed electroencephalography features. VE-CAM-S scores are strongly associated with clinical outcomes., Competing Interests: Dr. Kimchi was supported by the National Institutes of Health (NIH) (K08MH116135). Dr. Westover is a co-founder of Beacon Biosignals. Dr. Westover was supported by the Glenn Foundation for Medical Research and American Federation for Aging Research (Breakthroughs in Gerontology Grant); American Academy of Sleep Medicine (Foundation Strategic Research Award); Football Players Health Study at Harvard University; Department of Defense through a subcontract from Moberg ICU Solutions; and NIH (R01NS102190, R01NS102574, R01NS107291, RF1AG064312, R01AG062989). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objectives: Delirium is a common and frequently underdiagnosed complication in acutely hospitalized patients, and its severity is associated with worse clinical outcomes. We propose a physiologically based method to quantify delirium severity as a tool that can help close this diagnostic gap: the Electroencephalographic Confusion Assessment Method Severity Score (E-CAM-S)., Design: Retrospective cohort study., Setting: Single-center tertiary academic medical center., Patients: Three-hundred seventy-three adult patients undergoing electroencephalography to evaluate altered mental status between August 2015 and December 2019., Interventions: None., Measurements and Main Results: We developed the E-CAM-S based on a learning-to-rank machine learning model of forehead electroencephalography signals. Clinical delirium severity was assessed using the Confusion Assessment Method Severity (CAM-S). We compared associations of E-CAM-S and CAM-S with hospital length of stay and inhospital mortality. E-CAM-S correlated with clinical CAM-S (R = 0.67; p < 0.0001). For the overall cohort, E-CAM-S and CAM-S were similar in their strength of association with hospital length of stay (correlation = 0.31 vs 0.41, respectively; p = 0.082) and inhospital mortality (area under the curve = 0.77 vs 0.81; p = 0.310). Even when restricted to noncomatose patients, E-CAM-S remained statistically similar to CAM-S in its association with length of stay (correlation = 0.37 vs 0.42, respectively; p = 0.188) and inhospital mortality (area under the curve = 0.83 vs 0.74; p = 0.112). In addition to previously appreciated spectral features, the machine learning framework identified variability in multiple measures over time as important features in electroencephalography-based prediction of delirium severity., Conclusions: The E-CAM-S is an automated, physiologic measure of delirium severity that predicts clinical outcomes with a level of performance comparable to conventional interview-based clinical assessment., Competing Interests: Drs. Kimchi’s and Westover’s institutions received funding from the National Institutes of Health (NIH). Drs. Kimchi and Westover received support for article research from the NIH. Dr. Westover received funding from Beacon Biosignals. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Introduction: Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease with prevalence of approximately 1 in 5000-10,000. We evaluated the prevalence and association of cerebrovascular and cardiovascular comorbidities in HHT patients using national database., Methods: Retrospective observational study was performed using National Inpatient Sampling (NIS) database for the year 2014. HHT patients and comorbidities were identified using ICD-9 codes. Univariate and multivariate analyses were performed using SAS., Results: Prevalence of HHT was 0.0119% with predominance in White population. Mean age of HHT patients was 59 years. Increased proportion of HHT patients had hypertension (46.8% vs 42%), anemia (28.9% vs 15.1%), chronic pulmonary disease (24.8% vs 16.4%), congestive heart failure (15.7% vs 7.5%), liver disease (7.9% vs 2.8%), migraine (4.5% vs 1.5%), and cerebrovascular malformations (0.8% vs 0.03%), whereas chronic kidney disease (12.7% vs 12.2%), headaches (1.3% vs 1.1%), seizures (0.7% vs 0.9%), transient ischemic attacks (1.06% vs 1.03%), ischemic (1.2% vs 1.0%), and hemorrhagic (0.5% vs 0.3%) strokes were similar to those without HHT. Multivariable model shows increase in cerebrovascular malformations (OR 11.04, CI 2.49-22.26, p < 0.0001), migraine (OR 3.23, CI 2.30-4.52, p < 0.0001), chronic blood loss anemia (OR 6.83, CI 5.36-8.71, p < 0.0001), congestive heart failure (OR 1.55, CI 1.26-1.91, p < 0.0001), chronic pulmonary disease (OR 1.30, CI 1.09-1.56, p = 0.0038), and hepatic disease (OR 2.63, CI 2.01-3.45, p < 0.0001) in HHT patients as compared to non-HHT patients., Conclusion: There is a need for a large prospective registry of HHT patients that can corroborate these associations and burden of cerebrovascular and cardiovascular diseases., (© 2021. Fondazione Società Italiana di Neurologia.)

Staphylococcal mastitis (SM) is a frequent disease in the dairy cattle that is costly to treat. This study aimed to investigate the alterations in the levels of procalcitonin (PCT), neopterin (NPT), haptoglobin (HP), serum amyloid A (SAA), proinflammatory cytokines (IL-1 β , IL-8, TNF- α , IF- γ ) and oxidative stress (OS) biomarkers in Holstein dairy cows with SM under field conditions. In addition, we also evaluated the role of examined biomarkers in disease pathogenesis and their use as diagnostic biomarkers for the disease in dairy cows. Fifty-three dairy cows with SM, including those with infections caused by Staphylococcus aureus ( n  = 42) and methicillin resistant S. aureus (MRSA) ( n  = 11) were selected for this study. In addition, 20 healthy dairy cows were enrolled as a control group. Higher serum levels of PCT, NP, IL-1 β , IL-8, TNF- α , IF- γ , HP and SAA and a state of OS was detected in SM group in comparison with the controls. Moreover, the levels of all examined biomarkers in mastitic cows with S. aureus when compared with those infected with MRSA was not significantly different. All examined biomarkers demonstrated a significant degree of discrimination between SM cows and healthy controls (the area under the curve (AUC) ranged from 83.6 for S AA to 100 for PCT). Our study showed that SM in dairy cows was associated with substantial changes in serum PCT, NPT, Acute phase proteins (APPs), proinflammatory cytokines, and OS levels. This study demonstrates that clinical examination in tandem with quantification of PCT, NPT, APPs and cytokines, OS biomarkers could be a useful assessment tool for SM in dairy cows., Competing Interests: The authors declare there are no competing interests., (©2021 El-Deeb et al.)

Spinal cord injury (SCI) is a debilitating condition which often leads to a severe disability and ultimately impact patient's physical, psychological, and social well-being. The management of acute SCI has evolved over the couple of decades due to improved understanding of injury mechanisms and increasing knowledge of disease. Currently, the early management of acute SCI patient includes pharmacological agents, surgical intervention and newly experimental neuroprotective strategies. However, many controversial areas are still surrounding in the current treatment strategies for acute SCI, including the optimal timing of surgical intervention, early versus delayed decompression outcome benefits, the use of methylprednisolone. Due to the lack of consensus, the optimal standard of care has been varied across treatment centres. The authors have shed a light on the current updates on early treatment approaches and neuroprotective strategies in the initial management of acute SCI in order to protect the early neurologic injury and reduce the future disability., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Purpose of Review: Kumbh Mela , a religious gathering of Hindus held in India, is the largest massive gathering event in the world. The COVID-19 pandemic is an unprecedented healthcare crisis in recent times with effects reverberating in all spheres of human lives. India has registered the second highest number of COVID-19 cases. This paper aims to dwell in the religious and social background of Kumbh Mela massive gathering, as well as the ritualistic practices that could potentially entail public health risks in the current situation. It also aims to identify possible preparatory and interventional measures to evade such risks., Recent Findings: In recent years, the increase in the number of people attending the Kumbh Mela has been phenomenal. Congregants are put up at the holy sites for several days. The sheer number of people assembling at the religious venues poses a great challenge to manage the crowds, to cater to the requirements of basic amenities, and to meet their healthcare needs. Some of the ritualistic practices could heighten the risk for transmission of respiratory pathogens. The COVID-19 pandemic has escalated over the past few months in India. The pandemic is expected to sustain its tempo in India throughout the foreseeable future. Organization of the forthcoming Kumbh Mela needs meticulous planning., Summary: Kumbh Mela is a Hindu religious gathering at the banks of India's rivers, held periodically. It witnesses assembly of huge numbers of people and has the potential to amplify the COVID-19 pandemic in India; this could overwhelm the healthcare system., Competing Interests: Conflict of InterestSayed A. Quadri and Prasad R Padala declare that they have no conflict of interest, (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2021.)

Cannabidiol (CBD), which is nonintoxicating pharmacologically relevant constituents of Cannabis, demonstrates several beneficial effects. It has been found to have antioxidative, anti-inflammatory, and neuroprotective effects. As the medicinal use of CBD is gaining popularity for treatment of various disorders, the recent flare-up of largely unproven and unregulated cannabis-based preparations on medical therapeutics may have its greatest impact in the field of neurology. Currently, as lot of clinical trials are underway, CBD demonstrates remarkable potential to become a supplemental therapy in various neurological conditions. It has shown promise in the treatment of neurological disorders such as anxiety, chronic pain, trigeminal neuralgia, epilepsy, and essential tremors as well as psychiatric disorders. While recent FDA-approved prescription drugs have demonstrated safety, efficacy, and consistency enough for regulatory approval in spasticity in multiple sclerosis (MS) and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges still remain. In the current review, the authors have shed light on the application of CBD in the management and treatment of various neurological disorders.

Cerebrovascular malformations are uncommon diverse group of dysmorphic vascular communications that may occur sporadically or as part of genetic syndromes. These include non-neoplastic lesions such as arteriovenous malformations (AVM), cavernous malformations (CM), developmental venous anomalies (DVA), and telangiectasias as well as others like arteriovenous fistulas (AVF), vein of Galen malformations (VOGM), and mixed or unclassified angiomas. These lesions often carry a high degree of morbidity and mortality often requiring surgical or endovascular interventions. The field of cerebrovascular anomalies has seen considerable advancement in the last few years. Treatment and management options of various types of brain anomalies have evolved in neurological, neurosurgical, and neuro-interventional radiology arena. The use of radiological imaging studies is a critical element for treatment of such neurosurgical cases. As imaging modalities continue to evolve at a rapid pace, it is imperative for neurological surgeons to be familiar with current imaging modalities essential for a precise diagnosis. Better understanding of these cerebrovascular lesions along with their associated imaging findings assists in determining the appropriate treatment options. In the current review, authors highlight various cerebrovascular malformations and their current imaging modalities.

Functional disorders of the central nervous system (CNS) are diverse in terms of their etiology and symptoms, however, they can be quite debilitating. Many functional neurological disorders can progress to a level where pharmaceuticals and other early lines of treatment can no longer optimally treat the condition, therefore requiring surgical intervention. A variety of stereotactic and functional neurosurgical approaches exist, including deep brain stimulation, implantation, stereotaxic lesions, and radiosurgery, among others. Most techniques are invasive or minimally invasive forms of surgical intervention and require immense precision to effectively modulate CNS circuitry. Focused ultrasound (FUS) is a relatively new, safe, non-invasive neurosurgical approach that has demonstrated efficacy in treating a range of functional neurological diseases. It can function reversibly, through mechanical stimulation causing circuitry changes, or irreversibly, through thermal ablation at low and high frequencies respectively. In preliminary studies, magnetic resonance imaging-guided high-intensity focused ultrasound (MRgHIFU) has been shown to have long-lasting treatment effects in several disease types. The technology has been approved by the FDA and internationally for a number of treatment-resistant neurological disorders and currently clinical trials are underway for several other neurological conditions. In this review, the authors discuss the potential applications and emerging role of MRgHIFU in functional neurosurgery in the coming years., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Fiani et al.)

Study Objectives: Sleep is reflected not only in the electroencephalogram but also in heart rhythms and breathing patterns. We hypothesized that it is possible to accurately stage sleep based on the electrocardiogram (ECG) and respiratory signals., Methods: Using a dataset including 8682 polysomnograms, we develop deep neural networks to stage sleep from ECG and respiratory signals. Five deep neural networks consisting of convolutional networks and long- and short-term memory networks are trained to stage sleep using heart and breathing, including the timing of R peaks from ECG, abdominal and chest respiratory effort, and the combinations of these signals., Results: ECG in combination with the abdominal respiratory effort achieved the best performance for staging all five sleep stages with a Cohen's kappa of 0.585 (95% confidence interval ±0.017); and 0.760 (±0.019) for discriminating awake vs. rapid eye movement vs. nonrapid eye movement sleep. Performance is better for younger ages, whereas it is robust for body mass index, apnea severity, and commonly used outpatient medications., Conclusions: Our results validate that ECG and respiratory effort provide substantial information about sleep stages in a large heterogeneous population. This opens new possibilities in sleep research and applications where electroencephalography is not readily available or may be infeasible., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Inflammation is an important pathophysiological process after an acute stroke (AS). Pro- and anti-inflammatory molecules (cytokines and interleukins) are the key players during this mechanism. Emerging evidence indicate that these molecules can serve as biomarkers of stroke progression and outcome and as novel therapeutics agents. The aim of this study is to explore the temporal changes in these molecules and validate them as biomarker of AS progression and neurological outcome.The "Cytokine Registry In Stroke Patients (CRISP)" is a prospective cohort study of 600 AS patients presenting to the tertiary hospital with-in 24 h of the onset of symptoms. Plasma cytokines and interleukins will be collected at admission and 24 h after and will be measured using enzyme-linked immunosorbent assay (ELISA) to evaluate the difference in their variation among different gender, race and ethnicity and their association with various neurological outcomes. The primary exposures are biological sex (male, female) and race/ethnicity. Confounding variables include age, vascular risk factors, infarct size, stroke onset to presentation time, and identified stroke etiologies. Matched controls will be used for the comparison and evaluation of the difference among gender and race/ethnicities.CRISP is a prospective observational study that investigates the role and relationship of molecular biomarkers identifying specific and relevant targets pertinent for monitoring the progression and outcome in AS patients.Trial Registration: The study is registered on ClinicalTrial.gov: https://clinicaltrials.gov/ (NCT03297827).

Percutaneous nephrolithotomy (PCNL) despite its minimally invasive approach has an high complication rate, with the most common complications being extravasation of urine and perioperative bleeding requiring transfusion. While most of these complications are minor, many serious and life-threatening complications do occur. One such complication is the development of hemothorax or hydrothorax which usually develops in the early postoperative period with blood or urine passing from the surgical site through a newly established pleural-peritoneal fistula. Here we describe an unusual presentation and clinical management of delayed onset acute urohemothorax and hemodynamic collapse several days following PCNL.

The COVID-19 pandemic is ravaging the world. A principal preventive strategy is practicing social distancing. Congregations of the faithful at the local and transnational levels are strongly recommended by several world religions and religious orders, however, a gathering of large numbers of people in close approximation could be fertile ground for the spread of novel pathogens. The refusal to suspend such gatherings could lead to potential widespread dispersal of infections., (Copyright © 2020. Published by Elsevier Ltd.)

Spinal cord injury (SCI) is a life-shattering neurological condition that affects between 250,000 and 500,000 individuals each year with an estimated two to three million people worldwide living with an SCI-related disability. The incidence in the USA and Canada is more than that in other countries with motor vehicle accidents being the most common cause, while violence being most common in the developing nations. Its incidence is two- to fivefold higher in males, with a peak in younger adults. Apart from the economic burden associated with medical care costs, SCI predominantly affects a younger adult population. Therefore, the psychological impact of adaptation of an average healthy individual as a paraplegic or quadriplegic with bladder, bowel, or sexual dysfunction in their early life can be devastating. People with SCI are two to five times more likely to die prematurely, with worse survival rates in low- and middle-income countries. This devastating disorder has a complex and multifaceted mechanism. Recently, a lot of research has been published on the restoration of locomotor activity and the therapeutic strategies. Therefore, it is imperative for the treating physicians to understand the complex underlying pathophysiological mechanisms of SCI.

Competing Interests: There are no conflicts of interest.

Introduction Surgical residents play vital roles in day-to-day patient care as well as in the operating room. However, there is a paucity of literature regarding patients' perspectives on neurosurgical residents and their participation in their care. This current study investigates the knowledge, attitudes, and beliefs of patients regarding neurosurgical residents and their involvement in their healthcare process. Methods Patients older than 18 years who had undergone brain or spine surgery were requested to complete a survey questionnaire. The 7-point Likert scale response ranging from "strongly agree", "agree", "more or less agree", "undecided", more or less disagree", "disagree" to "strongly disagree" was used. The primary objective was to assess patient understanding and attitudes towards resident participation in surgical and medical care within the specialty of neurosurgery. The duration of the study was eight months. Patients having prior exposure to an informed-consent procedure by a neurosurgery team within a year prior to this study were excluded. Data were analyzed using Student's t-test, one-way analysis of variance (ANOVA), and standard averaging of responses. Results Fifty-one patients who had undergone elective surgery participated in the study survey. The majority of these respondents were between the ages of 46 and 60 years. Most of the responses were similar across gender and different age groups for most of the questions on the Likert scale questionnaire. Overall, when asked to assess their comfort level in medical and surgical care participation by residents, patients responded positively (strongly agree: 80.4%; agree: 92.2%). Patients also either disagreed or strongly disagreed (76%) about residents lacking medical knowledge. Patients overwhelmingly disagreed (91.5%) when asked if residents were unprofessional. In addition, 72.5% of the patients were able to accurately define a resident's role. Conclusion Well-formatted surveys can offer a convenient route for patients to provide objective as well as subjective feedback. The results indicate that patients had an overall positive attitude toward having residents involved in their care. These trends also indicate that patients knew the role that residents played in their healthcare process and they were comfortable with them doing so. Further studies may expand the trial to include a larger number of patients, as well as other specialties, to expand the scope of the study. Patient survey questionnaires could be thought of as a useful tool by the Accreditation Council for Graduate Medical Education (ACGME) to incorporate as part of the evaluation process of resident physicians., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Fiani et al.)

Introduction Burnout is common among clinical specialties and has implications on the residents' well-being and mental health. Evidence suggests that optimism and burnout are correlated, but research has not focused on the applicability to medical residents. The objective of the study was to define burnout in residents and correlate it with optimism. Methods The authors conducted a correlational, prospective cross-sectional study using self-reported single item burnout (1-10) and Life Oriented Test-Revised (LOT-R) (0-24) survey instruments among residents of neurosurgery, neurology, internal medicine, family medicine and emergency medicine at a community-based hospital. Residents were asked to fill out the survey once in the 2018 academic year and once again in the 2019 academic year. Burnout and optimism scores were correlated and compared across subgroups for each year. Results There was no statistical significance found amongst any subgroups in burnout in 2018 but significance was found for both internal medicine (t = 3.74, p = 0.001) and neurosurgery (t = -3.07, p = 0.01) in 2019. Mean burnout increased from 2018 to 2019 from 4.39 to 5.1. Optimism remained constant from 2018 to 2019 (16.7 and 16.76, respectively) and there was no difference across subgroups. There was a statistically significant negative correlation between burnout and optimism in both 2018 (r = -0.364, p = 0.006) and 2019 (r = -0.39, p = .001). Conclusion Burnout and optimism are negatively correlated. Although burnout increased over time, optimism remained constant indicating the stability of this trait and implication for future interventions., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Fowler et al.)

Whenever any new technology is introduced into the healthcare system, it should satisfy all three pillars of the iron triangle of health care, which are quality, cost-effectiveness, and accessibility. There has been quite advancement in the field of spine surgery in the last two decades with introduction of new technological modalities such as CAN and surgical robotic devices. MAZOR SpineAssist/Renaissance was the first robotic system to be approved for the use in spine surgeries in the USA in 2004. In this review, the authors sought to determine if the current literature supports this technology to be cost-effective, accessible, and improve the quality of care for individuals and populations by increasing the likelihood of desired health outcomes. Robotic-assisted surgery seems to provide perfection in surgical ergonomics and surgical dexterity, consequently improving patient outcomes. A lot of data is present on the accuracy, effectiveness, and safety of the robotic-guided technology which reflects remarkable improvements in quality of care, making its utility convincingly undisputable. The technology has been claimed to be cost-effective but there seems to be lack of data in the literature on this topic to validate this claim. Apart from just the outcome parameters, there is an immense need of studies on real-time cost-efficacy, patient perspective, surgeon and resident learning curve, and their experience with this new technology. Furthermore, new studies looking into increased utilities of this technology, such as brain and spine tumor resection, deep brain stimulation procedures, and osteotomies in deformity surgery, might authenticate the cost of the equipment.

Aim: The present study aimed to evaluate the alteration in the compressive strength (CS) of the die stone with three different sulfate salt additives, each at eight various concentrations., Materials and Methods: The specimens were prepared at specific dimensions (length: 2.5 cm and diameter: 2.5 cm) divided into three test groups based on the type of sulfate additives used [potassium sulfate (K 2 SO 4 ), zinc sulfate (ZnSO 4 ·H 2 O), and manganese sulfate (MnSO 4 ·H 2 O)] and one control group, without any additives. Again, each group was divided into eight subgroups based on concentration of sulfates (ranging from 0.2% to 4%). A total of 375 specimens were tested. CS (in MPa) was evaluated after 72 hours of drying time, using an universal testing machine., Statistical Analysis: A one-way analysis of variance (ANOVA) was used for intergroup comparisons. Individual comparisons were done using the post hoc Tukey HSD analysis., Results: All the three additives at all the concentrations have shown an inferior resistance to compressive forces when compared to the standard specimen. However, the least mean CS was observed at 0.8% of MnSO 4 (10.95 MPa) and the highest was at 1% K 2 SO 4 (25.28%). A highly significant difference ( p < 0.001) was observed among the concentrations in all the three groups (K 2 SO 4 , MnSO 4 , and ZnSO 4 groups) and F values were derived as 69.84, 24.29, and 130.52, respectively. At each concentration, comparisons between the groups have shown a significant difference ( p < 0.05) at almost all concentrations., Conclusion: The CS of die stone is shown to be decreased with an increase in all three types of sulfate additives when compared to the control specimen., Clinical Significance: Die stone is an often used gypsum material in the field of dentistry. Compressive strength of the die stone is crucial in prosthetic dentistry; chemical additives such as sulfate salts may increase the CS such that the die stone can withstand clinical and laboratory handling forces. How to cite this article: Vyas R, Vaddamanu SK, Gurumurthy V, et al. Variations in the Compressive Strength of a Die Stone with Three Different Sulfates at Eight Different Concentrations: An In Vitro Study. J Contemp Dent Pract 2019;20(11):1297-1306.

Study Design: A retrospective data review., Objective: To evaluate the efficacy of CyberKnife (CK) stereotactic radiosurgery (SRS) for thyroid spinal metastasis (SMs)., Summary of Background Data: Thyroid carcinoma is an infrequent cause of SM. The absolute efficacy of SRS generally and CK in particular remains poorly characterized for thyroid SM. The current study is the first to specifically evaluate the efficacy of CK SRS for thyroid SMs., Methods: A retrospective review of patients at our institution between 2003 and 2013 was done. Details about tumor location, radiographic findings before and after CK SRS, tumor recurrence, prescription isodose level, total and maximum dose, number of fractions, and gross tumor volume coverage were similarly collected. For comparison with other studies, the biologically effective dose and the equivalent total dose in 2 Gy fractions were calculated. Each patient was assessed for survival and local disease control from the time of the first CK session and survival analysis was carried out using the Kaplan-Meier method. Risk factors for local failure were assessed using multivariate logistic regression., Results: A total of 12 patients with 32 spinal metastases from thyroid carcinoma that were treated with CK SRS were identified. Survival for 1, 2, and 3 years was 55%, 44%, and 33%, and local control was 67%, 56%, and 34% respectively. The study found that the single strongest factor associated with local control was prior radiotherapy (β-coefficient -27.72, P = 0.01). No complications occurred in the immediate or late follow-up period., Conclusion: This was the first study to specifically investigate the efficacy of CK for treatment of thyroid SMs. Our findings suggest that CK can be safely used to treat spinal SMs from thyroid cancer and is associated with a high rate of local control., Level of Evidence: 4.

Background: Isolated brain metastasis (IBM) from cervical cancer is a very rare encounter in neurosurgery. We sought to understand how patients with isolated brain metastases differ from those with metastases in the setting of widespread disease., Methods: A systematic review was completed using PubMed and the Cochrane Library. Patients with isolated brain metastases (IBM) and non-isolated brain metastases (NIBM, or brain metastases in the setting of disseminated disease), were compared. Two-sided statistical tests were used to determine significance. Survival function was carried out using the Kaplan-Meier method., Results: A total of 89 patients, 25 with IBM and 64 with NIBM, were identified. The time interval between initial diagnosis of cervical cancer and diagnosis of brain lesion was significantly shorter in the IBM group (median 7.5 vs. 20.05 months, and IBM vs. NIBM, respectively; P = 0.006). Overall survival from initial diagnosis of cervical cancer was significantly shorter for the IBM group versus the NIBM group (7.63 vs. 26.3 months, respectively; P = 0.0005). Data demonstrate a 3.4-fold reduction of median life expectancy to 7.63 months. Survival after diagnosis of brain metastases did not differ between groups (median, IBM 7 months vs. NIBM 4 months, P = 0.08)., Conclusion: Taken together, our data suggest that for cervical cancer patients with brain metastasis intracranial metastasis itself (and not overall tumor burden) represent a sentinel event in limiting longevity. While the present study is underpowered to compare treatment options directly, further work should be focused on determining the optimal treatment for these patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Surgical Neurology International.)