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Background: The purpose of this retrospective analysis of a prospective quality control project was to determine whether the use of intrawound vancomycin powder (IVP) decreases the rate prosthetic joint infection (PJI) within 90-days following primary total knee arthroplasty (TKA)., Methods: From October 2021-September 2022, a prospective quality control project was undertaken in which 10 high-volume arthroplasty surgeons alternated between using IVP and not using IVP each month. Patients who received IVP were compared to those who did not. The primary outcome was culture positive PJI within 90-days following primary total knee arthroplasty. Secondary outcomes included overall reoperation rate, wound complications, and readmission within 90-days post-operatively., Results: A total of 1,317 primary TKA patients were identified for analysis. Fifty-six and seven tenths percent (n = 747) of patients were included in the IVP group and 43.3% (n = 570) patients were included in the non-IVP group. The overall PJI rate was 0.5%. There was no difference in 90-day culture positive PJI rates between the groups (0.7% vs. 0.2%, p = 0.24). The overall reoperation rate did not differ between the IVP and non-IVP group (6.4% vs. 4.6%, p = 0.15). Reoperation for suspected infection was not statistically different by IVP administration (1.2% vs. 0.5%, p = 0.25). Additionally, there were no differences in the incidence of wound complications (p = 0.80) or readmissions (p = 0.15)., Conclusions: The overall infection rate for this cohort was low. IVP was not associated with decreased culture positive PJI, wound complications, reoperation or readmission rates. Further analysis of IVP use in TKA should be undertaken to fully determine its efficacy and safety profile., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘Dr. Brian Cunningham’s spouse is the CEO and founder of CODE Technology. Dr. Cunningham is a member of the AAOS Health Care Systems and Patient-reported Outcome Measures Committees as well as the chair of the OTA Practice Management Committee. He is also a member of the editorial board for the Journal of Orthopaedic Business. The remaining authors have no conflicts of interest to disclose.’., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Study Objectives: To evaluate the concordance between visual scoring and automated detection of REM sleep without atonia (RSWA) and the validity and reliability of in-home automated-RSWA detection in REM sleep behavior disorder (RBD) patients and a control group (CG)., Methods: Sleep Profiler signals were acquired during simultaneous in-laboratory polysomnography in 24 isolated RBD patients. Chin and arm RSWA measures visually scored by an expert sleep technologist were compared to algorithms designed to automate RSWA detection. In a second cohort, the accuracy of automated-RSWA detection for discriminating between RBD and CG (n = 21 and 42, respectively) was assessed in multi-night in-home recordings., Results: For the in-laboratory studies, agreement between visual and auto-scored RSWA from the chin and arm were excellent, with intra-class correlations of 0.89 and 0.95, respectively, and substantial, based on Kappa scores of 0.68 and 0.74, respectively. For classification of iRBD patients versus controls, specificities derived from auto-detected RSWA densities obtained from in-home recordings were 0.88 for the chin, 0.93 for the arm, and 0.90 for the chin or arm, while the sensitivities were 0.81, 0.81 and 0.86, respectively. The night-to-night consistencies of the respective auto-detected RSWA densities were good based on intra-class correlations of 0.81, 0.79 and 0.84, however some night-to-night disagreements in abnormal RSWA detection were observed., Conclusions: When compared to expert visual RSWA scoring, automated RSWA detection demonstrates promise for detection of RBD. The night-to-night reliability of chin- and arm-RSWA densities acquired in-home were equivalent., (© 2024 American Academy of Sleep Medicine.)

Season of birth, viral infections, HLA haplogenotypes and non-HLA variants are implicated in the development of celiac disease and celiac disease autoimmunity, suggesting a combined role of genes and environmental exposures. The aim of the study was to further decipher the biological pathways conveying the season of birth effect in celiac disease autoimmunity to gain novel insights into the early pathogenesis of celiac disease. Interactions between season of birth, genetics, and early-life environmental factors on the risk of celiac autoimmunity were investigated in the multicenter TEDDY birth cohort study. Altogether 6523 genetically predisposed children were enrolled to long-term follow-up with prospective sampling and data collection at six research centers in the USA, Germany, Sweden and Finland. Celiac disease autoimmunity was defined as positive tissue transglutaminase antibodies in two consecutive serum samples. There was a significant season of birth effect on the risk of celiac autoimmunity. The effect was dependent on polymorphisms in CD247 gene encoding for CD3ζ chain of TCR-CD3 complex. In particular, children with major alleles for SNP rs864537A > G, in CD247 (AA genotype) had an excess risk of celiac autoimmunity when born March-August as compared to other months. The interaction of CD247 with season of birth on autoimmunity risk was accompanied by interactions with febrile infections between the ages of 3-6 months. Considering the important role of TCR-CD3 complex in the adaptive immune response and our findings here, CD247 variants and their possible effect of subgroups in autoimmunity development could be of interest in the design of future gene-environment studies of celiac disease. ClinicalTrials.gov Identifier: NCT00279318., (© 2024. The Author(s).)

Interpreting the phenotypes of bla SHV alleles in Klebsiella pneumoniae genomes is complex. Whilst all strains are expected to carry a chromosomal copy conferring resistance to ampicillin, they may also carry mutations in chromosomal bla SHV alleles or additional plasmid-borne bla SHV alleles that have extended-spectrum β-lactamase (ESBL) activity and/or β-lactamase inhibitor (BLI) resistance activity. In addition, the role of individual mutations/a changes is not completely documented or understood. This has led to confusion in the literature and in antimicrobial resistance (AMR) gene databases [e.g. the National Center for Biotechnology Information (NCBI) Reference Gene Catalog and the β-lactamase database (BLDB)] over the specific functionality of individual sulfhydryl variable (SHV) protein variants. Therefore, the identification of ESBL-producing strains from K. pneumoniae genome data is complicated. Here, we reviewed the experimental evidence for the expansion of SHV enzyme function associated with specific aa substitutions. We then systematically assigned SHV alleles to functional classes (WT, ESBL and BLI resistant) based on the presence of these mutations. This resulted in the re-classification of 37 SHV alleles compared with the current assignments in the NCBI's Reference Gene Catalog and/or BLDB (21 to WT, 12 to ESBL and 4 to BLI resistant). Phylogenetic and comparative genomic analyses support that (i) SHV-1 (encoded by bla SHV-1 ) is the ancestral chromosomal variant, (ii) ESBL- and BLI-resistant variants have evolved multiple times through parallel substitution mutations, (iii) ESBL variants are mostly mobilized to plasmids and (iv) BLI-resistant variants mostly result from mutations in chromosomal bla SHV . We used matched genome-phenotype data from the KlebNET-GSP AMR Genotype-Phenotype Group to identify 3999 K . pneumoniae isolates carrying one or more bla SHV alleles but no other acquired β-lactamases to assess genotype-phenotype relationships for bla SHV . This collection includes human, animal and environmental isolates collected between 2001 and 2021 from 24 countries. Our analysis supports that mutations at Ambler sites 238 and 179 confer ESBL activity, whilst most omega-loop substitutions do not. Our data also provide support for the WT assignment of 67 protein variants, including 8 that were noted in public databases as ESBL. These eight variants were reclassified as WT because they lack ESBL-associated mutations, and our phenotype data support susceptibility to third-generation cephalosporins (SHV-27, SHV-38, SHV-40, SHV-41, SHV-42, SHV-65, SHV-164 and SHV-187). The approach and results outlined here have been implemented in Kleborate v2.4.1 (a software tool for genotyping K. pneumoniae ), whereby known and novel bla SHV alleles are classified based on causative mutations. Kleborate v2.4.1 was updated to include ten novel protein variants from the KlebNET-GSP dataset and all alleles in public databases as of November 2023. This study demonstrates the power of sharing AMR phenotypes alongside genome data to improve the understanding of resistance mechanisms.

Rationale: Chronic obstructive pulmonary disease (COPD) is associated with increased risk of cardiovascular and cardiopulmonary events. In the Phase III, 52-week ETHOS trial (NCT02465567), triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF) reduced rates of moderate/severe exacerbations and all-cause mortality versus dual therapy with glycopyrrolate/formoterol fumarate (GFF) or budesonide/formoterol fumarate (BFF). However, the effect of BGF on cardiovascular events versus GFF remains unevaluated. Further, the effect of BGF on time to first severe exacerbation has not been reported. Objective: Assess the effects of BGF 320/18/9.6 μg (BGF 320) and other ICS-containing arms on cardiovascular and severe cardiopulmonary endpoints versus GFF in patients with COPD from ETHOS. Methods: Patients with moderate-to-very severe COPD and a history of exacerbations were randomized to twice-daily BGF 320, BGF 160/18/9.6 μg, BFF 320/9.6 μg, or GFF 18/9.6 µg (GFF). Time to first severe COPD exacerbation was a pre-specified endpoint; post-hoc cardiovascular and severe cardiopulmonary endpoints included time to first major adverse cardiac event (MACE), time to first cardiovascular adverse event (AE) of special interest (CVAESI), time to first cardiac AE, and time to the composite endpoint of first severe cardiopulmonary event. Measurements and Main Results: BGF 320 reduced the rate of first occurrence (hazard ratio [95% confidence interval]) of cardiovascular and severe cardiopulmonary events versus GFF, including for CVAESI (0.63 [0.48, 0.82]), cardiac AE (0.60 [0.48, 0.76]), and severe cardiopulmonary event (0.80 [0.67, 0.95]). Conclusions: BGF had a benefit on cardiovascular endpoints and severe cardiopulmonary events versus GFF in patients with moderate-to-very severe COPD.

Background: Targeted and efficient therapy strategies are necessary to address the global threat that chronic periodontitis poses to oral health. Antibiotic resistance is one drawback of traditional methods like scaling and root planing in conjunction with systemic antibiotics., Techniques: A study with 120 people who had been diagnosed with chronic periodontitis was done using randomized controlled trials. The subjects were grouped as the Feracrylum group and the placebo group. Clinical measures were measured at baseline and again after 12 weeks. These parameters included gingival index, clinical attachment level, and "probing pocket depth (PD)." A 3% solution was locally applied to periodontal pockets in the Feracrylum group, whereas a saline solution was given to the placebo group., Findings: As compared with other cohorts, the Feracrylum group showed a substantial improvement in clinical attachment level and a significant decrease in PD ( P < 0.05). Although not statistically significant, the gingival index reduction in the Feracrylum group showed a tendency in the direction of better gingival health., Conclusion: In summary, feracrylum has the potential as a localized medication delivery adjunct for chronic periodontitis, leading to positive clinical results. Larger sample numbers and longer follow-up times are required for future studies to confirm these results and maximize the use of feracrylum in periodontal treatment., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

To evaluate the utility of CD43 and CD200 in differentiating chronic lymphocytic leukemia (CLL) from other mature B-cell neoplasms. This was a cross-sectional study on patients diagnosed with B-cell neoplasms on flowcytometry. The median fluorescence intensity (MFI) of CD43, CD200 expressing neoplastic B-cells were compared between the CLL and non-CLL B-cell neoplasms followed by receiver operating characreristic curve (ROC) analysis. In addition, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CD43 and CD200 in diagnosing CLL were analysed. A total of 137 patients were included. The CLL group consisted 87 patients and non-CLL group consisted 50 patients. The Mann-Whitney U test showed significant CD43 expression (U = 997.5, Z= - 5.265, p  < 0.001) and CD200 expression (U = 932.0, Z = - 5.5, p  < 0.01) in CLL patients compared to non-CLL patients. The area under the curve were 0.771 and 0.786 for MFI of CD43 and CD200 in differentiating CLL from non-CLL group respectively. The optimal cut-off of MFI for CD43 and CD200 were 1323 and 1775 respectively. The sensitivity, specificity, PPV and NPV of CD43 in diagnosing CLL cases were 97.7%, 66%, 83.3% and 94.2% respectively. The sensitivity, specificity, PPV and NPV of CD200 in diagnosing CLL cases were 100%, 32%, 71.9% and 100% respectively. CD43 and CD200 are useful markers in differentiating CLL from other mature B-cell neoplasms with higher MFI expression of both markers found in CLL., Competing Interests: Conflict of interestNo conflict of interest., (© The Author(s), under exclusive licence to Indian Society of Hematology and Blood Transfusion 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: One common inflammatory illness that affects periodontal tissues is chronic periodontitis. By lowering inflammation and getting rid of periodontal bacteria, nonsurgical periodontal management is essential for treating chronic periodontitis. The objective of this study was to evaluate the effectiveness of chlorhexidine and feracrylum in nonsurgical periodontal management for persistent periodontitis., Techniques: As part of their periodontal therapy, 50 patients with a diagnosis of chronic periodontitis were randomized into two groups: first got chlorhexidine, while other Feracrylum received feracrylum. Microbiological analysis and clinical parameters were measured at baseline and 3 months later., Results: Clinical metrics showed a considerable improvement in both groups. Comparing feracrylum to chlorhexidine, the former showed stronger antibacterial action against periodontal infections., Conclusion: For nonsurgical periodontal management of chronic periodontitis, feracrylum shows similar effectiveness to chlorhexidine. Furthermore, feracrylum has better antibacterial activity against pathogens of the periodontal tissues, indicating that it might be used as a substitute antimicrobial agent in periodontal management., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Background/objectives: Epileptiform activity (EA), including seizures and periodic patterns, worsens outcomes in patients with acute brain injuries (e.g., aneurysmal subarachnoid hemorrhage [aSAH]). Randomized control trials (RCTs) assessing anti-seizure interventions are needed. Due to scant drug efficacy data and ethical reservations with placebo utilization, and complex physiology of acute brain injury, RCTs are lacking or hindered by design constraints. We used a pharmacological model-guided simulator to design and determine the feasibility of RCTs evaluating EA treatment., Methods: In a single-center cohort of adults (age >18) with aSAH and EA, we employed a mechanistic pharmacokinetic-pharmacodynamic framework to model treatment response using observational data. We subsequently simulated RCTs for levetiracetam and propofol, each with three treatment arms mirroring clinical practice and an additional placebo arm. Using our framework, we simulated EA trajectories across treatment arms. We predicted discharge modified Rankin Scale as a function of baseline covariates, EA burden, and drug doses using a double machine learning model learned from observational data. Differences in outcomes across arms were used to estimate the required sample size., Results: Sample sizes ranged from 500 for levetiracetam 7 mg/kg versus placebo, to >4000 for levetiracetam 15 versus 7 mg/kg to achieve 80% power (5% type I error). For propofol 1 mg/kg/h versus placebo, 1200 participants were needed. Simulations comparing propofol at varying doses did not reach 80% power even at samples >1200., Conclusions: Our simulations using drug efficacy show sample sizes are infeasible, even for potentially unethical placebo-control trials. We highlight the strength of simulations with observational data to inform the null hypotheses and propose use of this simulation-based RCT paradigm to assess the feasibility of future trials of anti-seizure treatment in acute brain injury., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background Congestive heart failure (CHF) is a leading cause of hospitalizations and readmissions, placing a significant burden on the healthcare system. Identifying factors associated with readmission risk is crucial for developing targeted interventions and improving patient outcomes. This study aimed to investigate the impact of socioeconomic and demographic factors on 30-day and 90-day readmission rates in patients primarily admitted for CHF. Methods The study was carried out using a cross-sectional study design, and the data were obtained from the Nationwide Readmissions Database (NRD) from 2016 to 2020. Adult patients with a primary diagnosis of CHF were included. The primary outcomes were 30-day and 90-day all-cause readmission rates. Multivariable logistic regression was used to identify factors independently associated with readmissions, including race, ethnicity, insurance status, income level, and living arrangements. Results A total of 219,904 patients with a primary diagnosis of CHF were used in the study. The overall 30-day and 90-day readmission rates were 17.3% and 23.1%, respectively. In multivariable analysis, factors independently associated with higher 30-day readmission risk included Hispanic ethnicity (OR 1.18, 95% CI 1.03-1.35), African American race (OR 1.15, 95% CI 1.04-1.28), Medicare insurance (OR 1.24, 95% CI 1.12-1.38), and urban residence (OR 1.11, 95% CI 1.02-1.21). Higher income was associated with lower readmission risk (OR 0.87, 95% CI 0.79-0.96 for highest vs. lowest quartile). Similar patterns were observed for 90-day readmissions. Conclusion Socioeconomic and demographic factors, including race, ethnicity, insurance status, income level, and living arrangements, significantly impact 30-day and 90-day readmission rates in patients with CHF. These findings highlight the need for targeted interventions and policies that address social determinants of health and promote health equity in the management of CHF. Future research should focus on developing and evaluating culturally sensitive, community-based strategies to reduce readmissions and improve outcomes for high-risk CHF patients., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mohyeldin et al.)

Background: The role of biceps tenodesis (BT) during open reduction internal fixation (ORIF) of proximal humerus fractures (PHFs) remains unclear. A subset of patients undergoing ORIF have persistent pain with unclear etiology. The purpose of our study was to compare outcomes of ORIF of PHFs with and without concomitant BT. We hypothesize patients undergoing BT at the time of ORIF will have improved patient-reported outcome scores with fewer secondary procedures related to treatment of the biceps., Methods: In this retrospective cohort study, all patients undergoing ORIF for a PHF at a single level one trauma center from January 2019 to June 2022 were reviewed. Patients under the age of 18 were excluded. Primary outcomes were patient-reported outcomes measurement information system physical function, depression, and pain interference scores at 5 time points up to final follow-up. Secondary outcomes included total operative time, complications, subsequent procedures, steroid injections, and range of motion. Chi-square tests were performed for categorical values and paired t-tests for continuous variables., Results: 71 patients met inclusion criteria: 41 undergoing ORIF without BT and 30 undergoing ORIF with BT. Average follow-up was 11 months. There were no statistically significant differences in patient demographics between groups. There were no differences in patient-reported outcomes measurement information system scores at any time point postoperatively. At final follow-up patients in the ORIF with BT group had higher forward flexion than those who did not undergo BT (142 vs. 123 degrees, respectively, P  < .02). There were no differences in surgical time, revision rates, postsurgical complications, or postoperative injections between groups., Conclusion: BT performed during ORIF of PHFs did not result in significantly different functional or patient-reported outcomes between groups, except for greater forward flexion at final follow-up. Although BT was done more commonly in severe PHFs, patients in both groups had similar rates of subsequent biceps-related procedures and revision surgery., (© 2024 The Authors.)

Background: The purpose of this study was to investigate whether decision-making regarding implant selection affects the reimbursement margins for the surgical fixation of ankle fractures., Methods: All ankle fractures treated between 2010 and 2017 within a single-insurer database were identified via Current Procedural Terminology codes by review of electronic medical record. Implant cost was determined via the implant record cross-referenced with the single contract institutional charge master database. The Time-Driven Activity-Based Costing (TDABC) technique was used to determine the costs of care during all activities throughout the 1-year episode of care. Statistical analysis consisted of multiple linear regression and goodness-of-fit analyses., Results: In all, 249 patients met inclusion criteria. Implant costs ranged from $173 to $3944, averaging $1342 ± $751. The TDABC-estimated cost of care ranged from $1416 to $9185, averaging $3869 ± $1384. Finally, the total reimbursed cost of care ranged between $1335 and $65 645, averaging $13 954 ± $9445. The implant costs occupied an estimated 34.7% of the TDABC-estimated cost of care per surgical encounter. Implant cost, as a percentage of the overall TDABC, was estimated as 36.2% in the inpatient setting and 33% in the outpatient setting, which was the second highest percentage behind surgical costs in both settings. We found a significant increase in net revenue of $1.93 for each dollar saved on implants in the outpatient setting, whereas the increase in net revenue per dollar saved of $1.03 approached significance in the inpatient setting., Conclusion: There is a direct relationship between intraoperative decision-making, as evidenced by implant choices, and the revenue generated by surgical fixation of ankle fractures. Intraoperative decision-making that is cognitive of implant cost can facilitate adoption of institutional cost containment measures and prompt increased healthcare value., Level of Evidence: Level III: Retrospective cohort study ., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Cunningham has received grant funding from Integra and his spouse is CEO of CODE Technology.

Mobile genetic elements are key to the global emergence of antibiotic resistance. We successfully reconstructed the complete bacterial genome and plasmid assemblies of isolates sharing the same bla KPC carbapenemase gene to understand evolution over time in six confined hospital drains over five years. From 82 isolates we identified 14 unique strains from 10 species with 113 bla KPC- carrying plasmids across 16 distinct replicon types. To assess dynamic gene movement, we introduced the 'Composite-Sample Complex', a novel mathematical approach to using probability to capture the directional movement of antimicrobial resistance genes. The Composite Sample Complex accounts for the co-occurrence of both plasmids and chromosomes within an isolate, and highlights likely gene donors and recipients. From the validated model, we demonstrate frequent transposition events of bla KPC from plasmids to other plasmids, as well as integration into the bacterial chromosome within specific drains. We present a novel approach to estimate the directional movement of antimicrobial resistance via gene mobilization., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

Objectives: Epileptiform activity (EA) worsens outcomes in patients with acute brain injuries (e.g., aneurysmal subarachnoid hemorrhage [aSAH]). Randomized trials (RCTs) assessing anti-seizure interventions are needed. Due to scant drug efficacy data and ethical reservations with placebo utilization, RCTs are lacking or hindered by design constraints. We used a pharmacological model-guided simulator to design and determine feasibility of RCTs evaluating EA treatment., Methods: In a single-center cohort of adults (age >18) with aSAH and EA, we employed a mechanistic pharmacokinetic-pharmacodynamic framework to model treatment response using observational data. We subsequently simulated RCTs for levetiracetam and propofol, each with three treatment arms mirroring clinical practice and an additional placebo arm. Using our framework we simulated EA trajectories across treatment arms. We predicted discharge modified Rankin Scale as a function of baseline covariates, EA burden, and drug doses using a double machine learning model learned from observational data. Differences in outcomes across arms were used to estimate the required sample size., Results: Sample sizes ranged from 500 for levetiracetam 7 mg/kg vs placebo, to >4000 for levetiracetam 15 vs. 7 mg/kg to achieve 80% power (5% type I error). For propofol 1mg/kg/hr vs. placebo 1200 participants were needed. Simulations comparing propofol at varying doses did not reach 80% power even at samples >1200., Interpretation: Our simulations using drug efficacy show sample sizes are infeasible, even for potentially unethical placebo-control trials. We highlight the strength of simulations with observational data to inform the null hypotheses and assess feasibility of future trials of EA treatment., Competing Interests: Potential Conflicts of Interest SFZ is a clinical neurophysiologist for Corticare and receives royalties from Springer for the publication Acute Neurology Survival Guide, independent of this work. M Brandon Westover is confounder of Beacon Biosignals, independent of this work.

Background: Epileptiform activity is associated with worse patient outcomes, including increased risk of disability and death. However, the effect of epileptiform activity on neurological outcome is confounded by the feedback between treatment with antiseizure medications and epileptiform activity burden. We aimed to quantify the heterogeneous effects of epileptiform activity with an interpretability-centred approach., Methods: We did a retrospective, cross-sectional study of patients in the intensive care unit who were admitted to Massachusetts General Hospital (Boston, MA, USA). Participants were aged 18 years or older and had electrographic epileptiform activity identified by a clinical neurophysiologist or epileptologist. The outcome was the dichotomised modified Rankin Scale (mRS) at discharge and the exposure was epileptiform activity burden defined as mean or maximum proportion of time spent with epileptiform activity in 6 h windows in the first 24 h of electroencephalography. We estimated the change in discharge mRS if everyone in the dataset had experienced a specific epileptiform activity burden and were untreated. We combined pharmacological modelling with an interpretable matching method to account for confounding and epileptiform activity-antiseizure medication feedback. The quality of the matched groups was validated by the neurologists., Findings: Between Dec 1, 2011, and Oct 14, 2017, 1514 patients were admitted to Massachusetts General Hospital intensive care unit, 995 (66%) of whom were included in the analysis. Compared with patients with a maximum epileptiform activity of 0 to less than 25%, patients with a maximum epileptiform activity burden of 75% or more when untreated had a mean 22·27% (SD 0·92) increased chance of a poor outcome (severe disability or death). Moderate but long-lasting epileptiform activity (mean epileptiform activity burden 2% to <10%) increased the risk of a poor outcome by mean 13·52% (SD 1·93). The effect sizes were heterogeneous depending on preadmission profile-eg, patients with hypoxic-ischaemic encephalopathy or acquired brain injury were more adversely affected compared with patients without these conditions., Interpretation: Our results suggest that interventions should put a higher priority on patients with an average epileptiform activity burden 10% or greater, and treatment should be more conservative when maximum epileptiform activity burden is low. Treatment should also be tailored to individual preadmission profiles because the potential for epileptiform activity to cause harm depends on age, medical history, and reason for admission., Funding: National Institutes of Health and National Science Foundation., Competing Interests: Declaration of interests MBW is a co-founder of Beacon Biosignals, which played no role in this study. SFZ is a clinical neurophysiologist consultant for Corticare. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

We propose a statistical framework ISLET to infer individual-specific and cell-type-specific transcriptome reference panels. ISLET models the repeatedly measured bulk gene expression data, to optimize the usage of shared information within each subject. ISLET is the first available method to achieve individual-specific reference estimation in repeated samples. Using simulation studies, we show outstanding performance of ISLET in the reference estimation and downstream cell-type-specific differentially expressed genes testing. We apply ISLET to longitudinal transcriptomes profiled from blood samples in a large observational study of young children and confirm the cell-type-specific gene signatures for pancreatic islet autoantibody. ISLET is available at https://bioconductor.org/packages/ISLET ., (© 2023. The Author(s).)

Freshwater and marine diatoms produce the majority of the oxygen in aquatic systems. Estimates range from 12,000 to 30,000 species, and spatial distribution varies globally. There is significant variation in diatom diversity based on geographical and environmental conditions as well as the physicochemical characteristics of the habitat. Therefore, understanding the underlying factors that contribute to changes in diatom community structures requires a comprehensive understanding of taxons. A study of diatom assemblages from the Cambay Basin, Western Arabian Sea, was conducted, particularly on oil fields. A total of 37 samples were collected; nine were from oil fields. We evaluated micro-oil spills using Fourier transform infrared (FTIR) analysis and microscopic techniques. Correlations were established through the ordination analysis of pernicious physical and chemical water variables (BOD, COD, TDS, pH, temperature, and DO), including principal component analysis (PCA). The oil field sites showed more total dissolved solids (TDS) and chemical oxygen demand (COD) than the respective marine control sites. The study does not display a cause-and-effect relationship, but we observed a positive correlation between increasing silica concentrations and diatom growth in oil fields. In contrast, high aluminium concentrations in oil fields negatively impacted the growth of diatom assemblage and abundance. When surveyed in nine oil fields, we found that Gomphonella pseudosphaerophorum and Nitzschia palea are well adapted to oil concentrations up to 40 ppm., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Achillea millefolium (Yarrow) is a herbaceous plant of Greek origin noted to treat pneumonia, common cold, cough, and other respiratory disorders. The flowers and leaves are the core part used to prepare herbal tea that gains the world's recognition as medicinal tea. Coronavirus disease is spreading across the globe, and numerous approaches are lodged to treat virus-induced lung inflammation. Here, we used the network pharmacology, metabolite analysis, docking and molecular simulation and MM-PBSA analysis to comprehend the biochemical basis of the health-boosting impact of Yarrow tea. Next, we performed the microscopic and dynamic light scattering (DLS) analysis of yarrow-treated ChAdOx1 nCoV-19 to evaluate the virucidal activity of the Yarrow. The present study investigates the druggability, metabolites and potential interaction of the title tea with genes associated with Covid-19-induced pathogenesis. Towards this, 1022 gene hits were obtained, 30 are mutually shared. Network Pharmacology and microarray gene expression analysis find the connection of PTGS2 in relieving the virus-induced inflammation. Yarrow constituents Luteolin may inhibit or down-regulate the Cyclooxygenase II (PTGS2), a plausible mechanism underlying the Yarrow's anti-inflammatory actions. Further, the Yarrow's virucidal activity was assessed towards Transmission Electron Microscopic (TEM). The Yarrow treated SARS-nCoV-2 cell exhibits the disintegration of the virus membrane. This work provides a scientific basis for further elucidating the mechanism underlying Achillea millefolium 's antiviral and anti-inflammatory properties.

There has been substantial excess morbidity and mortality during the COVID-19 pandemic, not all of which was directly attributable to SARS-CoV-2 infection, and many non-COVID-19 deaths were cardiovascular. The indirect effects of the pandemic have been profound, resulting in a substantial increase in the burden of cardiovascular disease and cardiovascular risk factors, both in individuals who survived SARS-CoV-2 infection and in people never infected. In this report, we review the direct effect of SARS-CoV-2 infection on cardiovascular and cardiometabolic disease burden in COVID-19 survivors as well as the indirect effects of the COVID-19 pandemic on the cardiovascular health of people who were never infected with SARS-CoV-2. We also examine the pandemic effects on health care systems and particularly the care deficits caused (or exacerbated) by health care delayed or foregone during the COVID-19 pandemic. We review the consequences of: (1) deferred/delayed acute care for urgent conditions; (2) the shift to virtual provision of outpatient care; (3) shortages of drugs and devices, and reduced access to: (4) diagnostic testing, (5) cardiac rehabilitation, and (6) homecare services. We discuss the broader implications of the COVID-19 pandemic for cardiovascular health and cardiovascular practitioners as we move forward into the next phase of the pandemic., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Diatom is a unicellular photosynthetic microalga that is found in diverse environments. These are decorated with siliceous cell walls called frustules. Diatoms have long been favoured by grazers such as microscopic protozoa and dinoflagellates. However, grazers typically remain intact in laboratory culturing and feed on diatom in culturing vessels and reducing biomass yield. The isolation and cultivation of diatoms in laboratories hamper diatoms' diversity and vast industrial potential. Chitosan, a biopolymer, has been widely used with other polyelectrolytes to flocculate various organic and inorganic colloids at acidic pH. Dissolved chitosan (acidic pH) has been used in various natural water samples and wastewater system for dewatering. However, untreated chitosan flakes have never been evaluated in a heterogeneous natural water environment. Since diatoms have silica surfaces, we tested chitosan for diatom separation and optimized chitosan concentration and other parameters to obtain grazer-free diatom starter culture from raw water. We also elucidated the mechanism for chitosan flakes-mediated diatom flocculation through adsorption kinetics and molecular dynamic simulation analysis. The results of this study are statistically optimized and validated, with a significant R 2 value of 0.99 for the proposed model.

Metagenomic sequencing is a promising new method for pathogen detection. We aimed to detect pathogens from archived plasma using metagenomic sequencing in a previously well-characterized cohort of 254 predominantly HIV-infected patients with sepsis in Uganda. We used Illumina sequencing and the Chan Zuckerberg ID metagenomics platform to sequence and identify pathogens. On average, each plasma sample yielded 3,404,737 ± 2,201,997 reads (mean ± standard deviation), of which 220,032 ± 416,691 (6.3% ± 8.6%) were identified as nonhuman reads. Using a background model filter, 414 genus-specific pathogen identifications were found in the 254 samples. Nineteen pathogens were previously detected positive by quantitative PCR (qPCR), compared to sequencing, which demonstrated 30.2% sensitivity and 99.5% specificity. Sensitivity was higher for viral pathogens than nonviral pathogens (37% versus 5%). For example, HIV viremia was detected in 69% of samples using qPCR, and sequencing revealed 70% sensitivity and 92% specificity. There were 75 genus-specific potential pathogens identified by sequencing in this cohort, including hepatitis B and Epstein-Barr virus (EBV), among several others. qPCR showed a prevalence of hepatitis B and EBV viremia of 17% and 45%, respectively. In-hospital mortality was associated with a lower qPCR threshold cycle value for EBV (adjusted odds ratio, 0.85; P  < .001) but not for hepatitis B or HIV. In conclusion, a broad range of potential pathogens were identified by metagenomic sequencing in patients with sepsis in Uganda. Unexpectedly high rates of hepatitis B and EBV viremia were found. Whether these viral infections in HIV patients with sepsis are clinically important requires further study. IMPORTANCE The use of next-generation sequencing (NGS) in blood samples is an emerging technology for clinical microbiology labs. In this work, we performed NGS on plasma samples from a well-characterized cohort, where all samples had been previously tested by PCR for 43 pathogens. Therefore, we could compare sequencing performance against that of PCR and identify clinical correlates. A broad range of potential pathogens were identified by metagenomic sequencing in patients with sepsis in Uganda, particularly viruses, which we confirmed by PCR. In addition to HIV viremia, unexpectedly high rates of hepatitis B and EBV viremia were found, which may have important clinical implications.

The identification of features that can improve classification accuracy is a major concern in land cover classification research. This paper compares deep learning and transform domain feature extraction techniques for land cover classification of SAR data on balanced and imbalanced training sets. Convolutional autoencoders (CAE), variational autoencoders (VAE), and Haar wavelet transforms (HWT) are used and evaluated for feature generation capability. Variations in features of CAE and HWT help gather more information about the image patch. The fusion of CAE and HWT features provides a combination of high- and low-frequency coefficients, respectively, which improves classification accuracy for various land covers. To assess features generated through fusion of features, RISAT-1 C-band and AIRSAR L-band datasets are used. Furthermore, agricultural/grass land has similar features with open forest which leads to misclassification of forest in agricultural/grass land. Increasing the number of samples in each class using the Synthetic Minority Oversampling Technique (SMOTE) increases training samples. Hierarchical classification of the above-mentioned features, where agricultural/grass land and forest classes are discriminated, improves classification results. This paper evaluates all the three types of features and fused features and provides a guidance for land cover classification., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ulnar Collateral Ligament (UCL) injuries are the most common thumb metacarpophalangeal joint ligamentinjury. Rehabilitation protocols traditionally permit return to sport at 12 weeks post-surgery. In this article, we propose anacellerated rehabilitation protocol permitting return to sport at 5-6 post-surgery in the recreational athlete., 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., (Published by Elsevier Inc.)

In July 2021, the Virginia Department of Health notified CDC of a cluster of eight invasive infections with Burkholderia stabilis, a bacterium in the Burkholderia cepacia complex (BCC), among hospitalized patients at hospital A. Most patients had undergone ultrasound-guided procedures during their admission. Culture of MediChoice M500812 nonsterile ultrasound gel used in hospital A revealed contamination of unopened product with B. stabilis that matched the whole genome sequencing (WGS) of B. stabilis strains found among patients. CDC and hospital A, in collaboration with partner health care facilities, state and local health departments, and the Food and Drug Administration (FDA), identified 119 B. stabilis infections in 10 U.S. states, leading to the national recall of all ultrasound gel products produced by Eco-Med Pharmaceutical (Eco-Med), the manufacturer of MediChoice M500812. Additional investigation of health care facility practices revealed frequent use of nonsterile ultrasound gel to assist with visualization in preparation for or during invasive, percutaneous procedures (e.g., intravenous catheter insertion). This practice could have allowed introduction of contaminated ultrasound gel into sterile body sites when gel and associated viable bacteria were not completely removed from skin, leading to invasive infections. This outbreak highlights the importance of appropriate use of ultrasound gel within health care settings to help prevent patient infections, including the use of only sterile, single-use ultrasound gel for ultrasonography when subsequent percutaneous procedures might be performed., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Splash basins are used in orthopaedic surgery cases to wash and hold instrumentsintraoperatively. This systematic review aims to summarize information on contamination of splash basins intraoperatively., Methods: A systematic review was conducted using the following search terms: "splash basin" or "splash bucket." Two authors independently reviewed the literature. Studies were included if they reported on intraoperative splash basin contamination rates. Studies were excluded if they were not relevant to orthopaedic surgery, non-English articles, or repeat studies yielded by different online databases., Results: There were seven studies included in this review. The median contamination rate of sterile water or physiologic saline splash basins was 23.9% [range: 2%-74%]. The addition of surgical antiseptics to sterile water splash basins was associated with 0% contamination rates in two studies. The most frequent splash basin contaminants identified in bacterial culture were coagulase negative staphylococcus (50%) and staphylococcus aureus (10%)., Conclusion: The splash basin appears to be a frequent source of contamination in the operating room. Many studies suggest abandoning splash basin use altogether, although the efficacy of alternative methods such as cleaning instruments with lap pads in avoiding contamination of the sterile field has not been studied. Further investigation into surgical teams' use of the splash basin and the contents of the splash basin as they relate to contamination rates may help advance our understanding of optimal use of this surgical tool. Shorter case durations and dilute surgical antiseptics in splash basins appear associated with lower splash basin contamination risk. Level of Evidence: V ., (Copyright © The Iowa Orthopaedic Journal 2022.)