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We previously showed that hepatic nitric oxide regulates net hepatic glucose uptake (NHGU), an effect that can be eliminated by inhibiting hepatic soluble guanylate cyclase (sGC), suggesting that the sGC pathway is involved in the regulation of NHGU. The aim of the current study was to determine whether hepatic cyclic guanosine monophosphate (cGMP) reduces NHGU. Studies were performed on conscious dogs with transhepatic catheters. A hyperglycemic-hyperinsulinemic clamp was established in the presence of portal vein glucose infusion. 8-Br-cGMP (50 µg/kg/min) was delivered intraportally, and either the glucose load to the liver (CGMP/GLC; n = 5) or the glucose concentration entering the liver (CGMP/GCC; n = 5) was clamped at 2× basal. In the control group, saline was given intraportally (SAL; n = 10), and the hepatic glucose concentration and load were doubled. 8-Br-cGMP increased portal blood flow, necessitating the two approaches to glucose clamping in the cGMP groups. NHGU (mg/kg/min) was 5.8 ± 0.5, 2.7 ± 0.5, and 4.8 ± 0.3, whereas the fractional extraction of glucose was 11.0 ± 1, 5.5 ± 1, and 8.5 ± 1% during the last hour of the study in SAL, CGMP/GLC, and CGMP/GCC, respectively. The reduction of NHGU in response to 8-Br-cGMP was associated with increased AMP-activated protein kinase phosphorylation. These data indicate that changes in liver cGMP can regulate NHGU under postprandial conditions. [ABSTRACT FROM AUTHOR]

This article first will explain the reasons behind and goals of state recoupment actions against the major cigarette manufacturers, their lobbying arm and trade association, and their public relations firms (collectively referred to as the 'tobacco industry') for the recovery of Medicaid and other indigent care expenditures on smoking-related illnesses. These are, primarily, to relieve the heavy financial burden on state treasuries and to stop the tobacco industry from targeting children in advertising and promotions. To put this new legal approach in perspective, the article presents a brief historical background to the tobacco industry's litigation strategy: to wear down opponents through delay and intimidation, to cast doubt on science, and to wrongfully invoke the attorney-client privilege against disclosure of incriminating evidence. Next authors discuss the states' strategy: each filing one suit seeking equitable remedies under theories of restitution/unjust enrichment, indemnity, public nuisance, and injunctive relief to protect the interests of minors, instead of maintaining thousands of product liability claims on behalf of individual smokers. This will be followed by a critique of the industry's response to state actions: political attacks against attorneys general and trial lawyers and charges that the lawsuits would hurt business as well as a variety of legal challenges, including an imaginative but risky defense that if smoking indeed causes disease and attendant health care expenditures, then the tobacco industry ought to be given a credit against those expenditures for the taxes generated by its business and the 'savings' which inure to the states from the premature deaths of smokers (the cost of geriatric care, for example). The article will wrap up by impressing on health officials and other readers what is at stake in these actions and what their success or failure will mean for the Medicaid program. [ABSTRACT FROM AUTHOR]

Background and Objectives: Many neonatal intensive care units (NICUs) do not give rotavirus vaccines to inpatients due to a theoretical risk of horizontal transmission of vaccine strains. We aimed to determine incidence and clinical significance of vaccine-strain transmission to unvaccinated infants in a NICU that routinely administers pentavalent rotavirus vaccine (RV5)., Methods: This prospective cohort study included all patients admitted to a 100-bed NICU for 1 year. Stool specimens were collected weekly; real-time quantitative reverse-transcription polymerase chain reaction was used to detect any RV5 strain. Incidence of transmission to unvaccinated infants was calculated assuming each unvaccinated patient's stool contributed 1 patient-day at risk for transmission. Investigations and geospatial analyses were conducted for suspected transmission events., Results: Of 1238 infants admitted, 560 (45%) were premature and 322 (26%) had gastrointestinal pathology. During observation, 226 RV5 doses were administered. Overall, 3448 stool samples were tested, including 2252 from 686 unvaccinated patients. Most (681, 99.3%) unvaccinated patients never tested positive for RV5 strain. Five (<1%) tested RV5 strain positive. The estimated rate of transmission to unvaccinated infants was 5/2252 stools or 2.2/1000 patient-days at risk (95% CI: 0.7-5.2). No gastroenteritis symptoms were identified in transmission cases within 7 days of collection of RV5-positive stool. Of 126 patients for whom the RV5 series was initiated before the discharge date, 55% would have become age-ineligible to start the series if vaccination was allowed only at discharge., Conclusions: Transmission of RV5 strain was infrequent and without clinical consequences. Benefits of allowing vaccine-induced protection against rotavirus disease in infants through in-NICU RV5 vaccination appear to have outweighed risks from vaccine-strain transmission., (Copyright © 2024 American Academy of Pediatrics.)

Glucose tolerance improves significantly upon consuming a second, identical meal later in the day (second meal phenomenon). We previously established that morning hyperinsulinemia primes the liver for increased afternoon hepatic glucose uptake (HGU). Although the route of insulin delivery is an important determinant of the mechanisms by which insulin regulates liver glucose metabolism (direct hepatic vs indirect insulin action), it is not known if insulin's delivery route affects the second meal response. To determine whether morning peripheral insulin delivery (as occurs clinically, i.e. subcutaneous) can enhance afternoon HGU, conscious dogs were treated in the morning with insulin delivered either via the portal vein or peripherally (leg vein), while glucose was infused to maintain euglycemia. Consequently, arterial insulin levels increased similarly in both groups, but relative hepatic insulin deficiency occurred with peripheral insulin delivery. In the afternoon, all animals were challenged with the same hyperinsulinemichyperglycemic clamp to simulate identical postprandial-like conditions. The substantial enhancement of HGU in the afternoon caused by morning portal vein insulin delivery was lost when insulin was delivered peripherally. This indicates that morning insulin does not cause the second meal phenomenon via its indirect actions on the liver, but rather through direct activation of hepatic insulin signaling., (© 2024 by the American Diabetes Association.)

(R,S)-Ketamine (ketamine) is a dissociative anesthetic that also possesses analgesic and antidepressant activity. Undesirable dissociative side effects and misuse potential limit expanded use of ketamine in several mental health disorders despite promising clinical activity and intensifying medical need. (2R,6R)-Hydroxynorketamine (RR-HNK) is a metabolite of ketamine that lacks anesthetic and dissociative activity but maintains antidepressant and analgesic activity in multiple preclinical models. To enable future assessments in selected human indications, we report the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of RR-HNK in a Phase 1 study in healthy volunteers (NCT04711005). A six-level single-ascending dose (SAD) (0.1-4 mg/kg) and a two-level multiple ascending dose (MAD) (1 and 2 mg/kg) study was performed using a 40-minute IV administration emulating the common practice for ketamine administration for depression. Safety assessments showed RR-HNK possessed a minimal adverse event profile and no serious adverse events at all doses examined. Evaluations of dissociation and sedation demonstrated that RR-HNK did not possess anesthetic or dissociative characteristics in the doses examined. RR-HNK PK parameters were measured in both the SAD and MAD studies and exhibited dose-proportional increases in exposure. Quantitative electroencephalography (EEG) measurements collected as a PD parameter based on preclinical findings and ketamine's established effect on gamma-power oscillations demonstrated increases of gamma power in some participants at the lower/mid-range doses examined. Cerebrospinal fluid examination confirmed RR-HNK exposure within the central nervous system (CNS). Collectively, these data demonstrate RR-HNK is well tolerated with an acceptable PK profile and promising PD outcomes to support the progression into Phase 2., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

The second-meal phenomenon refers to the improvement in glucose tolerance seen following a second identical meal. We previously showed that 4 h of morning hyperinsulinemia, but not hyperglycemia, enhanced hepatic glucose uptake (HGU) and glycogen storage during an afternoon hyperinsulinemic-hyperglycemic (HIHG) clamp. Our current aim was to determine if the duration or pattern of morning hyperinsulinemia is important for the afternoon response to a HIHG clamp. To determine this, the same total amount of insulin was administered either over 2 h in the first (Ins2h-A) or second (Ins2h-B) half of the morning or over the entire 4 h (Ins4h) of the morning. In the 4-h afternoon period, all three groups had 4x-basal insulin, 2x-basal glycemia, and portal glucose infusion to expose the liver to the primary postprandial regulators of hepatic glucose metabolism. During the afternoon clamp, there was a marked increase in HGU and hepatic glycogen synthesis in the Ins4h group compared with the Ins2h-A and Ins2h-B groups, despite matched hepatic glucose loads and total insulin infusion rates. Thus, the longer duration (Ins4h) of lower hyperinsulinemia in the morning seems to be the key to much greater liver glucose uptake during the afternoon clamp. NEW & NOTEWORTHY Morning insulin exposure primes the liver for increased hepatic glucose uptake and glycogen storage during a subsequent hyperinsulinemic-hyperglycemic clamp. This study addressed whether the pattern and/or duration of insulin delivery in the morning influences insulin's ensuing priming effect. We found that despite receiving equal total doses of insulin in the morning, a prolonged, lower rate of morning insulin delivery improved afternoon liver glucose metabolism more effectively than a shorter, higher rate of delivery.

Glucose tolerance improves significantly upon consuming a second, identical meal later in the day (second meal phenomenon). We previously established that morning hyperinsulinemia primes the liver for increased afternoon hepatic glucose uptake (HGU). Although the route of insulin delivery is an important determinant of the mechanisms by which insulin regulates liver glucose metabolism (direct hepatic vs indirect insulin action), it is not known if insulin's delivery route affects the second meal response. To determine whether morning peripheral insulin delivery (as occurs clinically (subcutaneous)) can enhance afternoon HGU, conscious dogs were treated in the morning with insulin delivered via the portal vein, or peripherally (leg vein), while glucose was infused to maintain euglycemia. Consequently, arterial insulin levels increased similarly in both groups, but relative hepatic insulin deficiency occurred when insulin was delivered peripherally. In the afternoon, all animals were challenged with the same hyperinsulinemic-hyperglycemic clamp to simulate identical postprandial-like conditions. The substantial enhancement of HGU in the afternoon caused by morning portal vein insulin delivery was lost when insulin was delivered peripherally. This indicates that morning insulin does not cause the second meal phenomenon via its indirect actions on the liver, but rather through direct activation of hepatic insulin signaling., Competing Interests: Conflict of Interest. A.D.C. has research contracts with Fractyl, Abvance, Fluidics, and Novo Nordisk, as well as grants from the NIH and the Helmsley Charitable Trust. A.D.C. is a consultant to Novo Nordisk, Paratus, Portal Insulin, Fractyl, and Thetis. No other individuals have conflicts of interest relevant to this article.

Background: Rotavirus is a leading cause of severe pediatric gastroenteritis; 2 highly effective vaccines are used in the United States (US). We aimed to identify correlates of immune response to rotavirus vaccination in a US cohort., Methods: Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal (PREVAIL) is a birth cohort of 245 mother-child pairs enrolled in 2017-2018 and followed for 2 years. Infant stool samples and symptom information were collected weekly. Shedding was defined as reverse-transcription polymerase chain reaction detection of rotavirus vaccine virus in stools collected 4-28 days after dose 1. Seroconversion was defined as a 3-fold rise in immunoglobulin A between the 6-week and 6-month blood draws. Correlates were analyzed using generalized estimating equations and logistic regression., Results: Prevaccination immunoglobulin G (IgG) (odds ratio [OR], 0.84 [95% confidence interval {CI}, .75-.94] per 100-unit increase) was negatively associated with shedding. Shedding was also less likely among infants with a single-nucleotide polymorphism inactivating FUT2 antigen secretion ("nonsecretors") with nonsecretor mothers, versus all other combinations (OR, 0.37 [95% CI, .16-.83]). Of 141 infants with data, 105 (74%) seroconverted; 78 (77%) had shed vaccine virus following dose 1. Prevaccination IgG and secretor status were significantly associated with seroconversion. Neither shedding nor seroconversion significantly differed by vaccine product., Conclusions: In this US cohort, prevaccination IgG and maternal and infant secretor status were associated with rotavirus vaccine response., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background: The use of ChatGPT (Generative Pretrained Transformer), which is a natural language artificial intelligence model, has gained unparalleled attention with the accumulation of over 100 million users within months of launching. As such, we aimed to compare the following: 1) orthopaedic surgeons' evaluation of the appropriateness of the answers to the most frequently asked patient questions after total hip arthroplasty; and 2) patients' evaluation of ChatGPT and arthroplasty-trained nurses responses to answer their postoperative questions., Methods: We prospectively created 60 questions to address the most commonly asked patient questions following total hip arthroplasty. We obtained answers from arthroplasty-trained nurses and from the ChatGPT-3.5 version for each of the questions. Surgeons graded each set of responses based on clinical judgment as 1) "appropriate," 2) "inappropriate" if the response contained inappropriate information, or 3) "unreliable" if the responses provided inconsistent content. Each patient was given a randomly selected question from the 60 aforementioned questions, with responses provided by ChatGPT and arthroplasty-trained nurses, using a Research Electronic Data Capture survey hosted at our local hospital., Results: The 3 fellowship-trained surgeons graded 56 out of 60 (93.3%) responses for the arthroplasty-trained nurses and 57 out of 60 (95.0%) for ChatGPT to be "appropriate." There were 175 out of 252 (69.4%) patients who were more comfortable following the ChatGPT responses and 77 out of 252 (30.6%) who preferred arthroplasty-trained nurses' responses. However, 199 out of 252 patients (79.0%) responded that they were "uncertain" with regard to trusting AI to answer their postoperative questions., Conclusions: ChatGPT provided appropriate answers from a physician perspective. Patients were also more comfortable with the ChatGPT responses than those from arthroplasty-trained nurses. Inevitably, its successful implementation is dependent on its ability to provide credible information that is consistent with the goals of the physician and patient alike., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Total hip arthroplasty (THA) for dislocated hips (Crowe IV dysplasia) presents unique challenges. Conventional approaches involve subtrochanteric osteotomies, but are complex with additional fixation and potentially lead to limb length discrepancies, nerve palsies, and other complications. An alternative strategy is a staged approach, where the femoral head (or remnant) is gradually lowered (distraction technique) to align with the true acetabulum over a period of time, followed by a second-stage anatomically acetabular-positioned THA. External fixation distraction and telescoping internal lengthening devices have been utilized to achieve preoperative alignment. We evaluated these techniques, including the types, time, and amount of distraction needed, as well as outcomes and complication rates., Methods: In this retrospective case series, 14 patients (9 women, 5 men), who had a mean age of 32 years (range, 16 to 67), underwent staged surgical interventions using hip distraction using external fixators or internal lengthening devices for hip dysplasia and other pathologies (Perthes disease, osteonecrosis) in preparation for a second-stage anatomically placed THA. The mean follow-up duration for external-fixation patients was 10 years (range, 6.5 to 13.4)., Results: Staged treatment involved external fixators (n = 8) or internal lengthening devices (n = 6) with a device placement mean of 48 days (range, 42 to 71). The amount of distraction ranged from 6 to 12 cm. There were 2 patients who required uncomplicated revision of the internal lengthening devices, and another patient had a temporary peroneal nerve palsy. There was 1 patient who underwent an acetabular revision at 7 years., Conclusions: We focused on a challenging patient cohort that emphasizes the efficacy of staged interventions in managing Crowe Type IV dysplasia and similar cases. Favorable outcomes were found with the immediate transition to THA after device removal that effectively addressed soft-tissue contractures and femoral migration. Despite the need for further validation via larger, prospective studies, this innovative approach may pave the way toward optimizing this strategy for these difficult hip pathologies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In 2021, alternative payment models accounted for 40% of traditional Medicare reimbursements. As such, we sought to examine health disparities through a standardized categorization of social disparity using the social vulnerability index (SVI). We examined (1) risk factors for SVI ≥ 0.50, (2) incidences of complications, and (3) risk factors for total complications between patients who have SVI < 0.50 and SVI ≥ 0.50 who had a total knee arthroplasty (TKA)., Methods: Patients who underwent TKA between January 1, 2022 and December 31, 2022 were identified in the state of Maryland. A total of 4,952 patients who had complete social determinants of health data were included. Patients were divided into 2 cohorts according to SVI: < 0.50 (n = 2,431) and ≥ 0.50 (n = 2,521) based on the national mean SVI of 0.50. The SVI identifies communities that may need support caused by external stresses on human health based on 4 themed scores: socioeconomic status, household composition and disability, minority status and language, and housing and transportation. The SVI theme of household composition and disability encompassed patients aged 65 years and more, patients aged 17 years and less, civilians who have a disability, single-parent households, and English language deficiencies. The higher the SVI, the more social vulnerability or resources are needed to thrive in a geographic area., Results: When controlling for risk factors and patient comorbidities, the theme of household composition and disability (odds ratio 2.0, 95% confidence interval 1.1 to 5.0, P = .03) was the only independent risk factor for total complications. Patients who had an SVI ≥0.50 were more likely to be women (65.8% versus 61.0%, P < .001), Black (34.4% versus 12.9%, P < .001), and have a median household income < $87,999 (21.3% versus 10.2%, P < .001) in comparison to the patients who had an SVI < 0.50, respectively., Conclusions: The SVI theme of household composition and disability, encompassing patients aged 65 years and more, patients aged 17 years and less, civilians who have a disability, single-parent households, and English language deficiencies, were independent risk factors for total complications following TKA. Together, these findings offer opportunities for interventions with selected patients to address social disparities., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In 2011, the American Academy of Orthopaedic Surgeons released a consensus recommending venous thromboembolism (VTE) prophylaxis after total knee arthroplasty (TKA). The purpose of our study was to examine (1) incidences of postoperative complications, including pulmonary embolism (PE), deep vein thrombosis (DVT), and transfusion rates; (2) trends from 2016 to 2021 in VTE prophylaxis; and (3) independent risk factors for 90-day total complications following TKA between aspirin, enoxaparin, rivaroxaban, and warfarin., Methods: Using a national, all-payer database from 2016 to 2021, we identified all patients who underwent primary TKA. Exclusions included all patients who had prescribed anticoagulants within 1 year prior to TKA, hypercoagulable states, and cancer. Data were collected on baseline demographics, including age, sex, diabetes, and a comorbidity index, in each of the VTE prophylaxis cohorts. Postoperative outcomes included rates of PE, DVT, and transfusion. Multivariable regressions were performed to determine independent risk factors for total complications at 90 days following TKA., Results: From 2016 to 2021, aspirin was the most used anticoagulant (n = 62,054), followed by rivaroxaban (n = 26,426), enoxaparin (n = 20,980), and warfarin (n = 13,305). The cohort using warfarin had the highest incidences of PE (1.8%) and DVT (5.7%), while the cohort using aspirin had the lowest incidences of PE (0.6%) and DVT (1.6%). The rates of aspirin use increased the most from 2016 to 2021 (32.1% to 70.8%), while the rates of warfarin decreased the most (19.3% to 3.0%). Enoxaparin, rivaroxaban, and warfarin were independent risk factors for total complications at 90 days., Conclusions: An epidemiological analysis of VTE prophylaxis use from 2016 to 2021 shows an increase in aspirin following TKA compared to other anticoagulant cohorts in a nationally representative population. This approach provides more insight and a better understanding of anticoagulation trends over this time period in a nationally representative sample., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Osteonecrosis of the femoral head (ONFH) poses a substantial burden to orthopaedic surgeons. However, the exact risk attributed by each specific patient factor for those who end up receiving a total hip arthroplasty (THA) are not well known. We assessed: (1) patient demographics (age and sex); (2) blood cell dyscrasias (sickle-cell disease and hypercoagulable states); and (3) substance use (oral corticosteroid use, tobacco use, and alcohol abuse)., Materials and Methods: A retrospective search examined all patients who had a primary THA (n=715,100) between January 1, 2010 and April 30, 2020 using a national, all-payer database. Risk factors studied included age, sex, sickle-cell, hypercoagulable state, oral corticosteroid use, tobacco use, and alcohol abuse., Results: Several risk factors were found to be significantly predictive for ONFH requiring THA: age <55 years (odds ratio [OR] 1.02, 95% confidence interval [CI] of 1.01 to 1.02, p<0.001), men (OR 1.07, 95% CI of 1.04 to 1.10, p<0.001), oral corticosteroid use (OR 1.21, 95% CI of 1.17 to 1.25, p<0.001), tobacco use (OR 1.15, 95% CI of 1.11 to 1.18, p<0.001), and alcohol abuse (OR 1.05, 95% CI of 1.01 to 1.08, p=0.009)., Conclusions: Based on the results of this study, young age, men, oral corticosteroid use, tobacco use, and alcohol abuse are risk factors for patients who have ONFH and had a THA. The degree of risk from greatest to least were: oral corticosteroid use, tobacco use, men, alcohol abuse, and age <55 years old.

This report provides an updated analysis for patients with osteoporosis following total hip arthroplasty (THA). The comorbidities of alcohol abuse, chronic kidney disease, cerebrovascular disease, obesity, and rheumatoid arthritis continue to be significant risk factors for periprosthetic femur fracture (PPFFx) and aseptic loosening in the population with osteoporosis. Patients with dual-energy x-ray absorptiometric (DEXA) scans were at risk for PPFFx regardless of femoral fixation method, and patients with DEXA scans with cementless fixation were at risk of aseptic loosening after THA. The patient population with severe osteoporosis may have higher risks for aseptic loosening and PPFFx than previously recognized., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Recent advances in total knee arthroplasty (TKA) have been driven by a growing focus on evidence-based medicine. This transition is reflected in the critical appraisal of both, the quality of work and the potential impact on the orthopedic community. The purpose of our study was to (1) identify the top 100 most-cited articles in TKA in the last decade and from all-time, and (2) compare methodological rigor of the most-cited articles in TKA in the last decade to articles all-time by level of evidence., Methods: The top 100 cited articles were recorded for manuscripts from the last decade, January 1, 2012 to December 31, 2022, and manuscripts from all-time for TKA. We collected authors, year of publication, journal of the article, country of origin of authors, article type (basic science article, clinical research article), level of evidence, methodological index for non-randomized studies score, physiotherapy evidence database scale, and citation density (total citations/years published)., Results: The largest number of studies for all-time TKA (53.0%) and decade TKA (42.0%) were Level III. The average methodological index for non-randomized studies score for comparative studies was 18.7 for all-time TKA and 20.7 for decade TKA (P < .001). The average physiotherapy evidence database score was 6.1 for all-time TKA and 8.1 for decade TKA (P > .05). The highest citation density for all-time TKA was 111 and for past decade was 63. The number of level II studies in TKA increased from 19.0% from all time to 38.0% from the last decade (P < .05)., Conclusions: Our findings of improved methodologies over time reflect positive steps toward evidence-based practice in TKA. A continued focus on producing methodologically sound studies may guide evidence-based clinical decision-making., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The mode of femoral fixation for primary total hip arthroplasty (THA) is undetermined, with reported outcomes favoring different fixation methods. This study aimed to compare postoperative complications between cemented and cementless fixation at 90 days, 1 year, and 2 years in patients aged 65 years of age and older undergoing THA for osteoarthritis., Methods: Using an all-payer, national database, patients 65 years and older undergoing primary THA, either with cementless (n = 56,701) or cemented (n = 6,283) femoral fixation for osteoarthritis were identified. A 1:1 propensity-matched analysis for age, sex, comorbidity index, alcohol abuse, tobacco use, obesity, and diabetes was performed, resulting in n = 6,283 patients in each cohort. Postoperative outcomes, including postoperative periprosthetic joint infection, aseptic revision, surgical site infection, pulmonary embolism, venous thromboembolism, wound complications, dislocation, periprosthetic fracture, and aseptic loosening were assessed., Results: The cemented cohort had higher rates of infection (4.5 versus 0.8%, odds ratio [OR] 5.9, 95% confidence interval [CI] 4.33 to 7.93, P < .001), aseptic revision (2.9 versus 2.0%, OR 1.47, 95% CI 1.17 to 1.85, P = .001), venous thromboembolism (1.8 versus 1.3%, OR 1.40, 95% CI 1.05 to 1.87, P < .001), and aseptic loosening (1.5 versus 0.7%, OR 2.31, 95% CI 1.60 to 3.32, P < .001) at 90-days. At 1 and 2 years, the cemented cohort had higher rates of infection, aseptic revision, and aseptic loosening (all P < .001). Rates of periprosthetic fracture were similar at all time points (all P < .001)., Conclusions: Cemented fixation had higher rates of infection, aseptic loosening, and aseptic revision. This finding supports the current use of cementless fixation, but the ultimate decision regarding fixation type should be based on the proper optimization of the patient's comorbidities and bone quality., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: There is continued debate regarding the survivorship and revision rate of cementless versus cemented total knee arthroplasty (TKA) prostheses. This includes the assessment of early revision surgery due to aseptic loosenings and periprosthetic joint infections (PJIs). Studies have not always taken into account the impact of comorbidities, such as diabetes, obesity, and tobacco. Therefore, we compared revisions in a large population of patients undergoing cemented or cementless TKAs at 90 days, 1 year, and 2 years., Methods: A review of an administrative claims database was used to identify patients undergoing primary TKA, either cementless (n = 8,890) or cemented (n = 215,460), from October 1, 2015 to October 31, 2020. Revision surgery for PJI and aseptic loosening were identified with diagnosis and associated procedural codes at 90 days, 1 year, and 2 years and then compared between groups. A propensity matched-analysis was performed for age, sex, Charles Comorbidity Index (CCI) > 3, alcohol abuse, tobacco use, obesity, and diabetes. Chi square tests assessed statistical significance of differences in the matched cohorts using odds ratios (ORs) with 95% confidence intervals (CIs). A P < 0.05 was defined as statistically significant., Results: Cementless TKA was associated with similar revisions rates due to PJIs at 90 days (OR, 1.04, 95% CI 0.79-1.38, p = 0.83), 1 year (OR, 0.93, 95% CI 0.75-1.14, p = 0.53, and 2 years (OR, 0.87, 95% CI 0.73-1.05, p = 0.17) in comparison to the cemented TKA cohort. The odds ratio of revision due to aseptic loosening was similar as well at 90 days (OR, 0.67, 95% CI 0.34-1.31, 0.31), 1 year (OR, 1.09, 95% CI 0.73-1.61, p = 0.76), and 2 years (OR, 1.00, 95% CI 0.73-1.61, p = 0.99)., Conclusions: This study found a comparable risk of PJI and aseptic loosening in cementless and cemented TKA when controlling for several comorbidities, such as tobacco, diabetes, and alcohol. Therefore, with proper patient selection, cementless TKAs can be performed with expectation of low risks of infections and aseptic loosenings., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Introduction: An increasing number of states are beginning to legalize recreational cannabis use, and as such, more patients using cannabis are undergoing shoulder arthroplasty procedures. The present study sought to examine the impact of cannabis use on post-operative outcomes. The primary outcomes of interest were postoperative complications, which included infection, periprosthetic fractures, periprosthetic joint infections (PJI), dislocations, and aseptic loosening as well as medical complications. Secondary outcomes were risk factors for PJI and aseptic loosening at two-years., Methods: A private, nationwide, all-payer database (Pearldiver Technologies) was queried to identify shoulder arthroplasty patients from 2010 to 2020. Those not using tobacco or cannabis ("control", n = 10,000), tobacco users (n = 10,000), cannabis users (n = 155), and concurrent tobacco and cannabis users (n = 9,842) were identified. Risk factors for PJI and aseptic loosening at two-years were further quantified utilizing multivariable logistic regression analysis., Results: Compared to non-users, cannabis users experienced the highest odds for PJI and aseptic revisions, which were followed by concurrent cannabis and tobacco users and tobacco-only users. Concurrent users, as well as tobacco users were at higher risk for dislocation. Cannabis use was the most significant risk factor for PJI, followed by concurrent use and male sex., Conclusions: Our study found cannabis use to cause greater risk for superficial and deep infection. More research involving randomized trials are needed to fully elucidate the impact of cannabis use on shoulder arthroplasty procedures. Clinically, these findings can appropriately guide surgeons and patients alike regarding expectations prior to undergoing TSA., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Of the targets for HIV-1 therapeutics, the capsid core is a relatively unexploited but alluring drug target due to its indispensable roles throughout virus replication. Because of this, we aimed to identify "clickable" covalent modifiers of the HIV-1 capsid protein (CA) for future functionalization. We screened a library of fluorosulfate compounds that can undergo sulfur(VI) fluoride exchange (SuFEx) reactions, and five compounds were identified as hits. These molecules were further characterized for antiviral effects. Several compounds impacted in vitro capsid assembly. One compound, BBS-103, covalently bound CA via a SuFEx reaction to Tyr145 and had antiviral activity in cell-based assays by perturbing virus production, but not uncoating. The covalent binding of compounds that target the HIV-1 capsid could aid in the future design of antiretroviral drugs or chemical probes that will help study aspects of HIV-1 replication., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: The gold standard to decrease total joint arthroplasty (TJA) periprosthetic joint infection (PJI) is preoperative antibiotic prophylaxis. Despite substantial prevention efforts, rates of PJIs are increasing. While cefazolin is the drug of choice for preoperative prophylaxis, adjunctive vancomycin therapy has been used in methicillin-resistant Staphylococcus aureus (MRSA) endemic areas. However, studies examining these combinations are lacking. Therefore, we sought to examine complications among vancomycin plus cefazolin and cefazolin-only recipients prior to primary TJA in a single institutional sample and specifically assessed: (1) microbiological aspects, including periprosthetic joint and surgical site infections, microbes cultured from the infection, and frequency of microbes cultured from nasal swab screening; (2) 30-day emergency department (ED) visits and re-admissions; as well as (3) associated risk factors for infection., Methods: A total of 2,907 patients (1,437 receiving both cefazolin and vancomycin and 1,470 given cefazolin only) who underwent primary TJA between 1 January 2014 and 31 May 2021 were identified. SSI and PJI as well as rates of cultured microbes rates were obtained through one year, those with prior nasal swab screening and 30-day re-admission were identified. Subsequently, multiple regression analyses were performed to investigate potential independent risk factors for PJIs., Results: There was no significant difference in the rates of SSI (P = 0.089) and PJI (P = 0.279) between the groups at one year after operation. Commonly identified organisms included Staphylococcus and Streptococcus species. The VC cohort did have a greater reduction of MRSA in the previously nasal swab-screened subset of patients. Multiple regression analyses demonstrated emergency as well as inpatient admissions as risk factors for PJI., Conclusions: Adjunctive vancomycin therapy offers increased protection against MRSA in previously screened individuals. However, those negative for MRSA screening do not require vancomycin and have similar protection to infection compared to recipients of cefazolin only in a high-powered single institution analysis in an MRSA endemic area., (© 2024. The Author(s).)

Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/H803).

Background: Distal femoral replacements (DFRs) are excellent treatment options for limb salvage procedures in patients who have bone loss secondary to neoplasm. Multiple studies report adequate survivorship and complication rates following DFR implantation, primarily for non-neoplastic indications. However, current literature regarding neoplasm-specific reports is often limited by sample size, survivorship, and patient reported outcome measurements. Therefore, we sought to examine patients who received a DFR for a neoplastic indication at multiple tertiary academic centers. Specific outcomes analyzed included: (1) revision-free survival, (2) medical/surgical complications, and (3) Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR)., Methods: All patients who underwent a DFR for a neoplastic indication were retrospectively reviewed. A total of 29 knees were included for various neoplastic indications. Outcomes of interest included: post-operative thromboses, pneumonia, dislocations, periprosthetic joint infections (PJIs), aseptic loosening, osteolysis, emergency department visits, inpatient readmissions, and revision surgeries. Patient-reported outcome measure (PROM) collected included: Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR)., Results: Revision-free survivorship was 72.4 % at 23 months with radiographic follow-up. PJI was the most common post-operative complication, affecting 3 knees (10.3 %). The mean number of emergency department visits and inpatient readmissions averaged less than one per patient (0.63 and 0.41, respectively). KOOS JR scores improved markedly among from baseline to final follow-up (44.1-57.8)., Conclusion: The use of DFR led to satisfactory medium-term clinical outcomes with an acceptable complication rate for this challenging group of patients. The marked improvement in patient satisfaction for this patient population gives a promising outlook for patients who will undergo this procedure in the future and can guide patient-provider regarding surgical expectations., Competing Interests: ZC- None. SB- None; JD- None. DH- None. CD- None. CS- None. MM- None; MW- None. RD-is a paid consultant for Microport Orthopedics, receives Research support from a company or supplier as a Principal Investigator from Microport Orthopedics, Stryker, United Orthopedic Corporation, on the Medical/Orthopaedic publications editorial/governing board of Journal of Arthroplasty, Journal of the American Osteopathic Medicine Association, Orthopedic Knowledge, Journal of Knee Surgery, Knee and Board member/committee appointments for a society. Of the arthritis foundation. AA- American Journal of Orthopedics: Editorial or governing boardAmgen Co: Stock or stock Options, Clinical Orthopaedics and Related Research: Editorial or governing board, Epizyme: Paid consultant, Journal of Bone and Joint Surgery - American: Editorial or governing board, Journal of the American Academy of Orthopaedic Surgeons: Editorial or governing board, Orthopedics: Editorial or governing board., (© 2024 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

This study examined the impact of a hypercaloric high-fat high-fructose diet (HFFD) in dogs as a potential model for human impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). The HFFD not only led to weight gain but also triggered metabolic alterations akin to the precursors of human T2DM, notably insulin resistance and β-cell dysfunction. Following the HFFD intervention, the dogs exhibited a 50% decrease in insulin sensitivity within the first four weeks, paralleling observations in the progression from normal to IGT in humans. Calculations of the insulinogenic index using both insulin and C-peptide measurements during oral glucose tolerance tests revealed a significant and sustained decrease in early-phase insulin release, with partial compensation in the later phase, predominantly stemming from reduced hepatic insulin clearance. In addition, the Disposition Index, representing the β-cell's capacity to compensate for diminished insulin sensitivity, fell dramatically. These results confirm that a HFFD can instigate metabolic changes in dogs akin to the early stages of progression to T2DM in humans. The study underscores the potential of using dogs subjected to a HFFD as a model organism for studying human IGT and T2DM., Competing Interests: Justin Gregory has served as an advisory board member for Sanofi, Eli Lilly, Medtronic, Dompe, vTv Therapeutics, and Mannkind Corporation and in data and safety monitoring roles for vTv Therapeutics and Medtronic. Alan Cherrington is a scientific advisor, consultant, and holds stock in Fractyl Laboratories. He also holds stock in Metavention. The other authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Gregory 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.)

Natural planned exposure (NPE) remains one of the most common methods in swine herds to boost lactogenic immunity against rotaviruses. However, the efficacy of NPE protocols in generating lactogenic immunity has not been investigated before. A longitudinal study was conducted to investigate the dynamics of genotype-specific antibody responses to different doses (3, 2 and 1) of Rotavirus A (RVA) NPE (genotypes G4, G5, P[7] and P[23]) in gilts and the transfer of lactogenic immunity to their piglets. Group 1 gilts received three doses of NPE at 5, 4 and 3 weeks pre-farrow (WPF), group 2 received two doses at 5 and 3 WPF, group 3 received one dose at 5 WPF, and group 4 received no NPE (control group). VP7 (G4 and G5) and truncated VP4* (P[7] and P[23]) antigens of RVA were expressed in mammalian and bacterial expression systems, respectively, and used to optimize indirect ELISAs to determine antibody levels against RVA in gilts and piglets. In day-0 colostrum samples, group 1 had significantly higher IgG titers compared to the control group for all four antigens, and either significantly or numerically higher IgG titers than groups 2 and 3. Group 1 also had significantly higher colostrum IgA levels than the control group for all antigens (except G4), and either significantly or numerically higher IgA levels compared to groups 2 and 3. In piglet serum, group 1 piglets had higher IgG titers for all four antigens at day 0 than the other groups. Importantly, RVA NPE stimulated antibodies in all groups regardless of the treatment doses and prevented G4, G5, P[7] and P[23] RVA fecal shedding prior to weaning in piglets in the absence of viral challenge. The G11 and P[34] RVA genotypes detected from pre-weaning piglets differed at multiple amino acid positions with parent NPE strains. In conclusion, the results of this study suggest that the group 1 NPE regimen (three doses of NPE) resulted in the highest anti-RVA antibody (IgG and IgA) levels in the colostrum/milk, and the highest IgG levels in piglet serum.

Introduction: The pleiotropic effects of statins extend beyond managing cardiovascular health and are suggested to modulate Staphylococcus aureus biofilm formation with prosthetic joint infection (PJI) reduction. However, a large analysis of statin use prior to total joint arthroplasty (TJA) to determine infection and revision risk is lacking. We specifically evaluated: 90-day to two-year (1) prosthetic joint infection (PJIs); (2) revisions; and (3) respective risk factors., Materials and Methods: We queried a national, all-payer database for patients undergoing either TKA or THA between 2010-2020. Chronic statin exposure was defined as >3 prescriptions filled within one-year prior to TJA (statin users). A control cohort of patients undergoing TJA without history of statin use prior was identified (statin naïve). Cohorts were matched 1:1 based on demographics and comorbidities (TKA: n=579,136; THA: n=202,092). Multivariate logistic regression was performed to evaluate risk factors for PJIs and revisions., Results: Among TKA recipients, statin users had lower incidence of PJIs at one year (0.36 vs. 0.39%) to two years (0.45 vs. 0.49%) compared to the statin naïve (all, p≤0.007). Similarly, statin users had lower incidence of one- to two-year revisions (all, p≤0.048). Among THA recipients, statin users had lower incidence of PJIs at 90 days (0.37 vs. 0.45%) to two years (2% vs. 2.14%) (all, p<0.001). Similar trends were observed for 90-day to two-year revisions (all, p≤0.022). Statin use was independently associated with decreased odds of PJIs and revisions by one year., Conclusions: Statin use is associated with a reduced risk of PJIs and revisions from one to two years following TJA. It may be worthwhile to ensure patients take statin therapy if indicated for previously established cardiovascular guidelines.

Introduction: In elderly patients who have proximal humerus fractures, treatment commonly involves total shoulder arthroplasty (TSA) or reverse shoulder arthroplasty (RSA). Following these procedures, patients often require opioids for postoperative analgesia. This common scenario is of clinical and societal importance, as increased postoperative opioid usage has been shown to worsen outcomes and increase the likelihood for dependence. We aimed to compare postoperative opioid use in patients undergoing either TSA or RSA for fixation of their proximal humerus fracture. Specifically, we assessed: (1) postoperative opioid use at two, four, six, eight, and greater than eight weeks postoperatively; (2) aseptic revision rates at 90-days, one year, and two years postoperatively; and (3) periprosthetic joint infection (PJI) rates at 90-days, one year, and two years postoperatively between patients undergoing TSA or RSA for the surgical management of their proximal humerus fractures., Materials and Methods: For this review, we queried a national all-payer database from October 1, 2015 to October 31, 2020 (n=1.5 million) for all patients who had a "proximal humerus fracture" diagnosis who underwent either TSA or RSA. There were two cohorts: patients undergoing TSA (n=731) and patients undergoing RSA (n=731). Bivariate Chi-square analyses., Results: We found no differences (p>0.05) in opioid use postoperatively in patients undergoing RSA for proximal humerus management compared to patients undergoing TSA after two weeks. There was not a significant difference in aseptic revision or PJI rates between the two cohorts (all p>0.05)., Conclusion: The evidence comparing opioid use in patients undergoing either TSA or RSA for proximal humerus fracture fixation is lacking. Our study specifically showed no differences in opioid use postoperatively in patients undergoing RSA for proximal humerus management compared to patients undergoing TSA.

Introduction: Venous thromboembolism (VTE) has long been acknowledged as a potential complication of total hip arthroplasty (THA) contributing to heightened patient morbidity, mortality, and substantial healthcare costs. We aimed to: 1) assess trends in VTE prophylaxis utilization between 2016 and 2021; 2) determine the incidence of postoperative VTE and transfusions; and 3) identify independent risk factors for 90-day VTE and transfusion risks following THA in relation to the use of aspirin, dabigatran, enoxaparin, rivaroxaban, and warfarin., Methods: A national, all-payer database was queried from January 1, 2016 and December 31, 2022. Use trends for aspirin, enoxaparin, rivaroxaban, dabigatran, and warfarin as thromboprophylaxis following THA was assessed. Incidence of ninety-day postoperative outcomes assessed included rates of 90-day postoperative VTE and transfusion., Results: From 2016 to 2021, aspirin (n = 36,346) was the most used agent for VTE prophylaxis after THA, followed by dabigatran (n = 13,065), rivaroxaban (n = 11,790), enoxaparin (n = 11,380), and warfarin (n = 6326). Independent risk factors for 90-day VTE included CKD, COPD, CHF, obesity, dabigatran, enoxaparin, rivaroxaban, and warfarin (all p  < 0.05)., Conclusion: Aspirin was used with increasing frequency and demonstrated lower rates of VTE and transfusion following THA, compared to dabigatran, enoxaparin, rivaroxaban, and warfarin. These findings seem to indicate that the increasing use of aspirin in VTE prophylaxis has been accomplished in appropriately selected patients., Competing Interests: JD- None. DH-None. JN- Arthritis Foundation: Board or committee member, Journal of Arthroplasty, Journal of the American Osteopathic Medicine Association, Orthopedic, Knowledge Online: Editorial or governing board, Journal of Knee Surgery: Editorial or governing board, Knee: Editorial or governing board, Microport: Paid consultant; Paid presenter or speaker; Research support, Stryker: Research support United: Research support RD- Baltimore City Medical Society.: Board or committee member, Biocomposites, Inc.: Research support, CyMedica Orthopedics: Research support, DePuy Synthes, Product, Inc.: Research support, Flexion Therapeutics: Research support, Microport Orthopedics, Inc.: Research support, Orthofix, Inc.: Research support, Patient-Centered Outcomes Research Institute (PCORI): Research support, Smith & Nephew: Research support, Stryker: Research support, Tissue Gene: Research support, United Orthopedic Corporation: Research support MM - None. SB - None., (© 2023 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

This study reports the coding-complete genome sequences of three rotavirus A (RVA) reference strains previously adapted in tissue culture: RVA/Mouse-tc/USA/EDIM/XXXX/G16P[16] with a G16-P[16]-I7-R7-C7-M8-A7-N7-T10-E7-H9 genotype constellation, RVA/Human-tc/USA/Ph158/1998/G9P[6] with a G9-P[6]-I2-R2-C2-M2-A2-N2-T2-E2-H2 genotype constellation, and RVA/Human-tc/USA/CC425/1998/G3P[9] with a G3-P[9]-I2-R2-C2-M2-A3-N2-T1-E2-H3 genotype constellation., Competing Interests: The authors declare no conflict of interest.

Background: The American Academy of Orthopaedic Surgeons (AAOS) provides clinical guidelines and frequently updates and expands on the recommendations. High quality, up-to-date, and applicable clinical guidelines are increasingly important tools for physicians to have. Assessing these continuously updating guidelines' overall quality has most recently been done in 2013 when there were 14 guidelines. Since then, nearly all guidelines have been updated and now 28 guidelines are provided. Our goal was to evaluate the updated 2023 AAOS guidelines using the well-established Advancing Guideline Development, Reporting and Evaluation in Health Care (AGREE II) tool., Methods: On April 23, 2023, all 28 guidelines set forth by AAOS were compiled. Using the AGREE II tool, a well-recognized and established tool for evaluation of guideline quality used across all disciplines, three independent reviewers appraised the current guidelines. These data were used to run descriptive statistics and assessed accordingly., Results: Across the 28 guidelines, the average AGREE II domain scores were as follows: Scope and Purpose (median score, 85%), Stakeholder Involvement (median score, 87%), Rigor of Development (median score, 87%), Clarity of Presentation (median score, 87%), Applicability (median score, 48%), Editorial Independence (median score, 87%), and Overall Assessment (median score, 80s%)., Conclusions: Five of the six AGREE II domains, including the overall assessment, tested achieved a median score above the 50% mark. These results indicate that the AAOS guidelines met many criteria for high quality based on a critical appraisal., (© 2023 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

Introduction: Arthrofibrosis occurs in up to 10% of patients who undergo total knee arthroplasty (TKA). For cases that are not amenable to manipulation under anesthesia (MUA), there is little consensus on how many components should be revised. We compared outcomes of polyethylene exchanges, when doing lysis of adhesions (LOA) versus full component revision. Specifically, we assessed: (1) re-operation rates at one and two years; (2) rates of surgical complications at one year; and (3) associated risk factors for requiring a LOA., Methods: A database queried all patients who underwent revision TKA for arthrofibrosis. A total of 2410 patients were identified, 1120 (46.5%) of which underwent all-component knee revision, while the remaining 1290 (53.5%) underwent polyethylene spacer revision. Multivariate logistic regressions assessed re-operation rates and risk factors for requiring LOA., Results: The incidence and odds of re-operation within one year following polyethylene exchange was not significantly different than full component revision (10.9 versus 12.9%, odds ratio (OR) 0.83, 95% confidence interval (CI) [0.64-1.06], p  = 0.145). However, the adjusted models for re-operation within one- and two-years following LOA in the form of polyethylene exchange revision was significantly higher than the full component revision cohort (OR 1.52 CI [1.07-2.17], p = 0.022 and OR 1.44 CI [1.06-1.97] p = 0.022). Risk factors associated with the need for lysis of adhesions included age less than 60 years, depression, fibromyalgia, and anxiety., Conclusions: Full component revision TKA for arthrofibrosis was associated with lower two-year re-operation rate than polyethylene exchange. Risk factors for LOA include younger age and fibromyalgia., Competing Interests: ZC- None. SB- None. JD- None. DH- None. OS- None. MM- None. SP- None. RD-is a paid consultant for Microport Orthopedics, receives Research support from a company or supplier as a Principal Investigator from Microport Orthopedics, Stryker, United Orthopedic Corporation, on the Medical/Orthopaedic publications editorial/governing board of Journal of Arthroplasty, Journal of the American Osteopathic Medicine Association, Orthopedic Knowledge, Journal of Knee Surgery, Knee and Board member/committee appointments for a society Of the arthritis foundation. JN- receives research support from Johnson & Johnson, Biocomposites, CyMedica Orthopedics, Depuy Synthes Product, Flexion Therapeutics, Microport, Orthopedics, Orthofix, Patient-Centered Outcomes Research Institute (PCORI), Smith & Nephew, Stryker, Tissue Gene, United Orthopedic Corporation, is a Medical/Orthopaedic publications editorial/governing board for Journal of Knee Surgery and Board member/committee appointments for a society for Baltimore City Medical Society., (© 2023 Published by Elsevier B.V. on behalf of Professor P K Surendran Memorial Education Foundation.)

Angelman Syndrome is a rare, genetically induced neurodevelopmental disorder. This disorder stems from a mutation or deletion of the maternal UBE3A gene. Characteristics of this disease include developmental delay, recurring seizures, and severe intellectual disabilities. We studied seizure activity in male Drosophila melanogaster with a knockdown of Ube3a in different neuronal populations (GABAergic, glutamatergic, mushroom body, and all neurons) and investigated the effects of the antiseizure medication (ASM) on seizure-like activity. Epileptiform activity was monitored in individual fruit flies using imaging chambers and mechanically induced seizures using a vortex assay. A positive control was also used: eas ( easily shocked seizure phenotype). Seizure activity was analyzed for sums of seizure durations, number of seizures, and total time to return to normal activity.  Ube3a knockdowns in GABAergic neurons elicited more seizure-like episodes than knockdowns in glutamatergic neurons and were on par with the positive control group and those with knockdowns in the mushroom bodies. We have established a method whereby valproate could be administered through food rather than through injections to effectively treat epileptiform activity. We demonstrated that if Ube3a is not knocked down pan-neuronally, Angelman Syndrome seizure-like activity can be studied using Drosophila melanogaster and therefore allows for high-throughput drug discovery., 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., (© 2023 The Authors.)

Objective: The objective of this study was to qualitatively examine coping mechanisms and desired supports in pregnant and birthing Black and Biracial adolescent and young adult women during the COVID-19 pandemic., Methods: Black and Biracial participants ages 16-23 were recruited for virtual individual semi-structured interviews. Participants (n = 25) were asked about pre- and post-natal experiences with the healthcare system, effects of the pandemic, and participants' experiences of or desires for ideal care within the healthcare system. Interviews were transcribed verbatim and coded for qualitative analysis using nVivo. Discussions around postpartum mental health evolved organically when asked about how participants were coping postpartum., Results: Nearly half the interviewees organically reported mental health symptoms consistent with postpartum depression (PPD) during questions regarding their postpartum experience. Of the 11 interviewees who reported mental health symptoms consistent with PPD, 2 were afraid to disclose their symptoms to a healthcare provider due to fear of child protective services involvement and their belief they would be treated unfairly because of their race., Conclusion: Clinicians who care for Black and Biracial adolescent and young adult mothers must be particularly attuned to structural barriers for appropriate screening and treatment of postpartum depression. Expanding investigations of intersectional influences on young mothers' perinatal health and PPD are needed., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: An increase in the number of policy initiatives, such as alternative payment models, have prompted healthcare providers to examine health-care expenditures while seeking to improve quality of care. Performing total joint arthroplasty (TJA) in the outpatient setting is an attractive option in driving costs down and providing psychological benefits to patients. Concerns regarding the safety and effectiveness of same-day discharge protocols warrants further investigation, especially on the state level. Due to the lack of consensus, we aimed to compare: (1) risk factors for outpatient arthroplasty and (2) incidences of postoperative complications between inpatient vs outpatient arthroplasty using an in-state database., Methods: Patients who underwent total knee or hip arthroplasty between January 1, 2022 and December 31, 2022 were identified. Data was drawn from the Maryland State Inpatient Database (SID) and Maryland State Ambulatory Surgery and Services Database (SASD). A total of 7817 patients had TJA within this time. Patients were divided into inpatient arthroplasty (n = 1429) and outpatient arthroplasty (n = 6338). Demographic variables, medical comorbidities, and 90-day complication rates were compared between inpatient and outpatient procedures. Additional independent variables included: marital status, primary language, race, and median household income. A multivariate logistic regression analysis was performed to identify independent risk factors for complications following TJA after controlling for risk factors and patient comorbidities., Results: Arthroplasty in the outpatient setting were more likely to be married (61.3% vs. 51.2%, p < 0.001), white (75.5% vs. 60.9%, <0.001), speak English as primary language (98.7% vs. 88.6%, p < 0.001), and have lower rates of diabetes (4.8% vs. 9.7%, p < 0.001), chronic obstructive pulmonary disease (16.3% vs. 21.8%, p < 0.001), and obesity (30.0% vs. 45.2%, p < 0.001) compared to arthroplasty in the inpatient setting, respectively. There were lower incidences of acute kidney injury (0.2 vs. 0.8%, p < 0.001) and infection (0.3% vs. 1.1%, p < 0.001) in the outpatient cohort compared to the inpatient cohort, respectively. Inpatient arthroplasty (Odds Ratio (OR) 1.98, 95% CI 1.30-3.02, p = 0.002) and hypertension (OR 2.12, 95% CI 1.23-3.64, p = 0.007) were independent risk factors for total complications following TJA., Conclusion: Arthroplasty in the outpatient setting showed fewer complications than compared to patients in the inpatient setting. Although multiple factors should guide the decision for arthroplasty, outpatient arthroplasty may be a safe option for select, healthier patients without the increased burden of increased complications., (© 2023 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

Introduction: Revision total hip arthroplasty (rTHA) is at increased risk for postoperative instability when compared to primary cases, which has been mitigated to some extent with the introduction of dual mobility (DM) reconstructions. These constructs were designed to lower dislocation rates and to improve impingement-free range of motion. As a follow-up to our prior institutional study, we expanded on a cohort of DM reconstructions compared to non-DM constructs. We examined a modular dual mobility system in rTHA to measure loosening of the acetabular component, as well as revision and dislocation rates in comparison to an historical cohort of single articulation prostheses.Materials/Methods: This retrospective cohort study from a single center included 254 patients who underwent rTHA with a dual mobility liner by three fellowship-trained surgeons between January 1, 2014 and December 1, 2019. This was a follow-up to an historical cohort of revisions performed with a single articulation prosthesis (n = 120) from the same surgeons performed between January 1, 2011 and December 23, 2013. The inclusion criteria included consecutively performed rTHAs that had a minimum follow-up of 2 years. We excluded patients who had femoral revisions and head/liner revisions only. The average follow-up in the dual mobility cohort and the single articulation cohort was 5 years (range, 2-10 years) and 2.5 years (range, 1.5-4.3 years), respectively. The primary outcomes were dislocation, aseptic loosening, and re-revision rates. Secondary outcomes were radiographic analyses of cup migration and osteolysis., Results: There were 4 out of 256 (1.6%) dislocations from the dual mobility cohort compared to 7 out of 120 (5.8%), P  < 0.001 from the single articulation cohort. The rates of aseptic loosening were 3.2% (8 out of 254) and 4.2% (5 out of 120), P  = 0.124, respectively, between the cohorts. The re-revision rate was 5.9% for the DM liners and 8.3% in the control cohort, P  = 0.38. Radiographic analyses revealed no cup migration and osteolysis in any of the patients that had no dislocations., Conclusion: The dual mobility articulations in rTHA demonstrated improved results in terms of lower dislocations rates when compared to a single articulation prostheses. Our center uses these articulations for revisions and surgeons should consider the use of these bearings when performing rTHA., (© 2023 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

We performed deep metagenomic sequencing on hydrocarbon-degrading marine microcosms designed to experimentally determine the effect of photo-oxidation on oil biodegradation dynamics. Assembly, binning, and dereplication yielded 73 unique metagenome-assembled genomes (MAGs) from 6 phyla, of which 61 are predicted to be over 90% complete., Competing Interests: The authors declare no conflict of interest.

In this study, we report the detection of a G6P[14] rotavirus strain from a human stool sample within the United States. The full genotype constellation of the G6P[14] strain was identified as G6-P[14]-I2-R2-C2-M2-A11-N2-T6-E2-H3., Competing Interests: The authors declare no conflict of interest.

Objective: The objective of this study was to qualitatively examine coping mechanisms and desired supports in pregnant and birthing Black and biracial adolescent and young adult women during the COVID-19 pandemic. Method: Black and biracial participants ages 16-23 were recruited for virtual individual semi-structured interviews. Participants (n=25) were asked about pre- and post-natal experiences with the healthcare system, effects of the pandemic, and participants' experiences of or desires for ideal care within the healthcare system. Interviews were transcribed verbatim and coded for qualitative analysis using nVivo. Discussions around postpartum mental health evolved organically when asked about how participants were coping postpartum. Results: Nearly half the interviewees reported mental health symptoms consistent with postpartum depression (PPD). Of the 11 interviewees who reported mental health symptoms consistent with PPD, 2 were afraid to disclose their symptoms to a healthcare provider due to fear of child protective services involvement and their belief they would be treated unfairly because of their race. Conclusion: Clinicians who care for Black and biracial adolescent and young adult mothers must be particularly attuned to structural barriers for appropriate screening and treatment of postpartum depression. Expanding investigations of intersectional influences on young mothers' perinatal health and PPD are needed.

Sustaining, maintaining, and upgrading the electricity grid, while meeting decarbonization goals is a challenge facing policymakers, regulators, grid operators, and investors. Simultaneously meeting demands for future capacity, retiring older inefficient technologies, and addressing externalities from energy production and use requires more diverse and inclusive technologies to avoid constraints and shortfalls in grid capability. Changing the energy production paradigm by encouraging alternative technologies was a key driver for FERC Order 2222. This stimulus for developing new small-scale generation will complement and supplement the existing fleet only if it attracts new investment. This investment must reflect technology that goes beyond the energy-only characteristics of traditional generation, creating systems where suites of energy-equivalent outputs are enhanced by environmental quality benefits and offsets. We use energy system designs to highlight the contribution that measuring and accounting for equivalency values provides net increases in capacity, electricity, and alternative fuels while simultaneously reducing carbon waste impacts., Competing Interests: The authors declare no competing interests., (© 2021.)