Ribosomal frameshifting selectively modulates the assembly, function, and pharmacological rescue of a misfolded CFTR variant.

The cotranslational misfolding of the cystic fibrosis transmembrane conductance regulator chloride channel (CFTR) plays a central role in the molecular basis of CF. The misfolding of the most common CF variant (ΔF508) remodels both the translational regulation and quality control of CFTR. Nevertheless, it is unclear how the misassembly of the nascent polypeptide may directly influence the activity of the translation machinery. In this work, we identify a structural motif within the CFTR transcript that stimulates efficient -1 ribosomal frameshifting and triggers the premature termination of translation. Though this motif does not appear to impact the interactome of wild-type CFTR, silent mutations that disrupt this RNA structure alter the association of nascent ΔF508 CFTR with numerous translation and quality control proteins. Moreover, disrupting this RNA structure enhances the functional gating of the ΔF508 CFTR channel at the plasma membrane and its pharmacological rescue by the CFTR modulators contained in the CF drug Trikafta. The effects of the RNA structure on ΔF508 CFTR appear to be attenuated in the absence of the ER membrane protein complex, which was previously found to modulate ribosome collisions during "preemptive quality control" of a misfolded CFTR homolog. Together, our results reveal that ribosomal frameshifting selectively modulates the assembly, function, and pharmacological rescue of a misfolded CFTR variant. These findings suggest that interactions between the nascent chain, quality control machinery, and ribosome may dynamically modulate ribosomal frameshifting in order to tune the processivity of translation in response to cotranslational misfolding.

Differentiation of Prior SARS-CoV-2 Infection and Postacute Sequelae by Standard Clinical Laboratory Measurements in the RECOVER Cohort.

BACKGROUND: There are currently no validated clinical biomarkers of postacute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: To investigate clinical laboratory markers of SARS-CoV-2 and PASC. DESIGN: Propensity score-weighted linear regression models were fitted to evaluate differences in mean laboratory measures by prior infection and PASC index (≥12 vs. 0). (ClinicalTrials.gov: NCT05172024). SETTING: 83 enrolling sites. PARTICIPANTS: RECOVER-Adult cohort participants with or without SARS-CoV-2 infection with a study visit and laboratory measures 6 months after the index date (or at enrollment if >6 months after the index date). Participants were excluded if the 6-month visit occurred within 30 days of reinfection. MEASUREMENTS: Participants completed questionnaires and standard clinical laboratory tests. RESULTS: Among 10 094 participants, 8746 had prior SARS-CoV-2 infection, 1348 were uninfected, 1880 had a PASC index of 12 or higher, and 3351 had a PASC index of zero. After propensity score adjustment, participants with prior infection had a lower mean platelet count (265.9 × 109 cells/L [95% CI, 264.5 to 267.4 × 109 cells/L]) than participants without known prior infection (275.2 × 109 cells/L [CI, 268.5 to 282.0 × 109 cells/L]), as well as higher mean hemoglobin A1c (HbA1c) level (5.58% [CI, 5.56% to 5.60%] vs. 5.46% [CI, 5.40% to 5.51%]) and urinary albumin-creatinine ratio (81.9 mg/g [CI, 67.5 to 96.2 mg/g] vs. 43.0 mg/g [CI, 25.4 to 60.6 mg/g]), although differences were of modest clinical significance. The difference in HbA1c levels was attenuated after participants with preexisting diabetes were excluded. Among participants with prior infection, no meaningful differences in mean laboratory values were found between those with a PASC index of 12 or higher and those with a PASC index of zero. LIMITATION: Whether differences in laboratory markers represent consequences of or risk factors for SARS-CoV-2 infection could not be determined. CONCLUSION: Overall, no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC. PRIMARY FUNDING SOURCE: National Institutes of Health.

Resumption of Cardiac Activity after Withdrawal of Life-Sustaining Measures.

BACKGROUND: The minimum duration of pulselessness required before organ donation after circulatory determination of death has not been well studied. METHODS: We conducted a prospective observational study of the incidence and timing of resumption of cardiac electrical and pulsatile activity in adults who died after planned withdrawal of life-sustaining measures in 20 intensive care units in three countries. Patients were intended to be monitored for 30 minutes after determination of death. Clinicians at the bedside reported resumption of cardiac activity prospectively. Continuous blood-pressure and electrocardiographic (ECG) waveforms were recorded and reviewed retrospectively to confirm bedside observations and to determine whether there were additional instances of resumption of cardiac activity. RESULTS: A total of 1999 patients were screened, and 631 were included in the study. Clinically reported resumption of cardiac activity, respiratory movement, or both that was confirmed by waveform analysis occurred in 5 patients (1%). Retrospective analysis of ECG and blood-pressure waveforms from 480 patients identified 67 instances (14%) with resumption of cardiac activity after a period of pulselessness, including the 5 reported by bedside clinicians. The longest duration after pulselessness before resumption of cardiac activity was 4 minutes 20 seconds. The last QRS complex coincided with the last arterial pulse in 19% of the patients. CONCLUSIONS: After withdrawal of life-sustaining measures, transient resumption of at least one cycle of cardiac activity after pulselessness occurred in 14% of patients according to retrospective analysis of waveforms; only 1% of such resumptions were identified at the bedside. These events occurred within 4 minutes 20 seconds after a period of pulselessness. (Funded by the Canadian Institutes for Health Research and others.).

Avian influenza A viruses exhibit plasticity in sialylglycoconjugate receptor usage in human lung cells.

IMPORTANCE: It is well known that influenza A viruses (IAV) initiate host cell infection by binding to sialic acid, a sugar molecule present at the ends of various sugar chains called glycoconjugates. These sugar chains can vary in chain length, structure, and composition. However, it remains unknown if IAV strains preferentially bind to sialic acid on specific glycoconjugate type(s) for host cell infection. Here, we utilized CRISPR gene editing to abolish sialic acid on different glycoconjugate types in human lung cells, and evaluated human versus avian IAV infections. Our studies show that both human and avian IAV strains can infect human lung cells by utilizing any of the three major sialic acid-containing glycoconjugate types, specifically N-glycans, O-glycans, and glycolipids. Interestingly, simultaneous elimination of sialic acid on all three major glycoconjugate types in human lung cells dramatically decreased human IAV infection, yet had little effect on avian IAV infection. These studies show that avian IAV strains effectively utilize other less prevalent glycoconjugates for infection, whereas human IAV strains rely on a limited repertoire of glycoconjugate types. The remarkable ability of avian IAV strains to utilize diverse glycoconjugate types may allow for easy transmission into new host species.

The Landscape of Gold Nanocrystal Surface Chemistry.

ConspectusGold nanoparticles (AuNPs) exhibit unique size- and shape-dependent properties not obtainable at the macroscale. Gold nanorods (AuNRs), with their morphology-dependent optical properties, ability to convert light to heat, and high surface-to-volume ratios, are of great interest for biosensing, medicine, and catalysis. While the gold core provides many fascinating properties, this Account focuses on AuNP soft surface coatings, which govern the interactions of nanoparticles with the local environments. Postmodification of AuNP surface chemistry can greatly alter NP colloidal stability, nano-bio interactions, and functionality. Polyelectrolyte coatings provide controllable surface-coating thickness and charge, which impact the composition of the acquired corona in biological settings. Covalent modification, in which covalently bound ligands replace the original capping layer, is often performed with thiols and disulfides due to their ability to replace native coatings. N-heterocyclic carbenes and looped peptides expand the possible functionalities of the ligand layer.The characterization of surface ligands bound to AuNPs, in terms of ligand density and dynamics, remains a challenge. Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for understanding molecular structures and dynamics. Our recent NMR work on AuNPs demonstrated that NMR data were obtainable for ligands on NPs with diameters up to 25 nm for the first time. This was facilitated by the strong proton NMR signals of the trimethylammonium headgroup, which are present in a distinct regime from other ligand protons' signals. Ligand density analyses showed that the smallest AuNPs (below 4 nm) had the largest ligand densities, yet spin-spin T2 measurements revealed that these smallest NPs also had the most mobile ligand headgroups. Molecular dynamics simulations were able to reconcile these seemingly contradictory results.While NMR spectroscopy provides ligand information averaged over many NPs, the ligand distribution on individual particles' surfaces must also be probed to fully understand the surface coating. Taking advantage of improvements in electron energy loss spectroscopy (EELS) detectors employed with scanning transmission electron microscopy (STEM), a single-layer graphene substrate was used to calibrate the carbon K-edge EELS signal, allowing quantitative imaging of the carbon atom densities on AuNRs with sub-nanometer spatial resolution. In collaboration with others, we revealed that the mean value for surfactant-bilayer-coated AuNRs had 10-30% reduced ligand density at the ends of the rods compared to the sides, confirming prior indirect evidence for spatially distinct ligand densities.Recent work has found that surface ligands on nanoparticles can, somewhat surprisingly, enhance the selectivity and efficiency of the electrocatalytic reduction of CO2 by controlling access to the active site, tuning its electronic and chemical environment, or denying entry to impurities that poison the nanoparticle surface to facilitate reduction. Looking to the future, while NMR and EELS are powerful and complementary techniques for investigating surface coatings on AuNPs, the frontier of this field includes the development of methods to probe the surface ligands of individual NPs in a high-throughput manner, to monitor nano-bio interactions within complex matrices, and to study structure-property relationships of AuNPs in biological systems.

Analysis of seizure-cluster circadian periodicity from a long-term, open-label safety study of diazepam nasal spray.

OBJECTIVE: Seizure clusters require prompt medical treatment to minimize possible progression to status epilepticus, increased health care use, and disruptions to daily life. Isolated seizures may exhibit cyclical patterns, including circadian and longer rhythms. However, little is known about the cyclical patterns in seizure clusters. This post hoc analysis of data from a long-term, phase 3, open-label, repeat-dose safety study of diazepam nasal spray modeled the periodicity of treated seizure clusters. METHODS: Mixed-effects cosinor analysis evaluated circadian rhythmicity, and single component cosinors using 12 and 24 h were used to calculate cosinor parameters (e.g., midline statistic of rhythm, wave ampitude, and acrophase [peak]). Analysis was completed for the full cohort and a consistent cohort of participants with two or more seizure clusters in each of four, 3-month periods. The influence of epilepsy type on cosinor parameters was also analyzed. RESULTS: Seizure-cluster events plotted across 24 h showed a bimodal distribution with acrophases (peaks) at ~06:30 and ~18:30. A 12-h plot showed a single peak at ~06:30. Cosinor analyses of the full and consistent cohort aligned, with acrophases for both models predicting peak seizure activity at ~23:30 on a 24-h scale and ~07:30 on a 12-h scale. The consistent cohort was associated with increases in baseline and peak seizure-cluster activity. Analysis by epilepsy type identified distinct trends. Seizure clusters in the focal epilepsy group peaked in the evening (acrophase 19:19), whereas events in the generalized epilepsy group peaked in the morning (acrophase 04:46). Together they compose the bimodal clustering observed over 24 h. SIGNIFICANCE: This analysis of seizure clusters treated with diazepam nasal spray demonstrated that seizure clusters occur cyclically in 12- and 24-h time frames similar to that reported with isolated seizures. Further elucidation of these patterns may provide important information for patient care, ranging from improved patient-centered outcomes to seizure-cluster prediction.

Childhood Sexual Abuse and Compulsive Sexual Behavior Among Men Who Have Sex with Men Newly Diagnosed with HIV.

Childhood sexual abuse (CSA) continues to be a public health challenge. The prevalence of experiencing CSA is higher among men who have sex with men (MSM) than the general population. CSA has been linked to compulsive sexual behavior (CSB) among varying populations but has not been examined among MSM who were newly diagnosed with HIV. Therefore, the aims of this study were to assess the direct association between CSA and CSB among newly diagnosed MSM living with HIV, and to identify the potential mediating roles of depressive symptoms and emotion regulation in the association between CSA and CSB. The study was a secondary data analysis using data obtained from 2012 to 2017 from two community HIV clinics in New York City (n = 202). CSA was operationalized with questions asking about sexual abuse during childhood/adolescence. CSB was measured using the 13-item Compulsive Sexual Behavior Inventory (CSBI). Depressive symptoms were measured using the 20-item Centers for Epidemiologic Studies Depression (CES-D) scale and emotion regulation was measured using a 36-item Difficulties in Emotion Regulation Scale (DERS). Path analysis was conducted to determine the mediating role of depressive symptoms and emotion regulation in the association between CSA and CSB. There was a statistically significant association between CSA and CSB (ß = 0.160; p = 0.019). There were statistically significant indirect associations between CSA, depressive symptoms, emotion regulation, and CSB (depressive symptoms ß = 0.0.071; p = 0.010; DERS: ß = 0.080; p = 0.006). Depressive symptoms were also correlated with emotion regulation (r = 0.596; p < 0.001). The relationship between CSA and CSB was significantly mediated by depressive symptoms and emotion regulation. Trauma-informed interventions addressing depressive symptoms and difficulties in emotion regulation may help to reduce CSB among MSM living with HIV.

Childhood sexual abuse and antiretroviral therapy adherence among older adults living with HIV: a mixed methods study.

Findings on the association between childhood sexual abuse (CSA) and antiretroviral therapy (ART) adherence have been varied, with some studies showing a relationship, or a lack thereof. However, to our knowledge, no study has examined this association among older adults living with HIV (OALH). Therefore, the purpose of this study was to examine the association between CSA and ART adherence among OALH using a mixed methods approach. This study, which involved a concurrent design, had two phases. The first phase comprised in-depth, semi-structured interviews of 24 adults aged 50 and older living with HIV in South Carolina. The second phase included data from 91 OALH. Thematic analysis and multivariable regression models, adjusting for age, gender, race, and income, were used to determine the association between CSA and ART adherence. The main theme emerging from the qualitative data was that CSA was not linked with ART adherence. However, contrastingly, quantitative analyses revealed a negative statistically significant association between CSA and ART adherence (adjusted ß: -3.35; 95% CI: -5.37, -1.34). This difference in findings could be due to the hidden impact of trauma and/or the use of different study populations. Future research should assess mediating pathways between CSA and ART adherence.

Preclinical toxicity studies supporting 2DG for treatment of status epilepticus.

2-deoxy-D-glucose (2DG) has been proposed as a potential antiseizure treatment based on seizure suppressive actions in multiple acute and chronic seizure models, including models of status epilepticus (SE). Here we summarize recently completed preclinical toxicological studies of single doses of an intravenous formulation of 2DG supporting potential safety of 2DG for acute treatment of SE and acute repetitive seizures (ARS).

Epilepsy monitoring unit practices and safety among NAEC epilepsy centers: A census survey.

OBJECTIVE: An epilepsy monitoring unit (EMU) is a specialized unit designed for capturing and characterizing seizures and other paroxysmal events with continuous video electroencephalography (vEEG). Nearly 260 epilepsy centers in the United States are accredited by the National Association of Epilepsy Centers (NAEC) based on adherence to specific clinical standards to improve epilepsy care, safety, and quality. This study examines EMU staffing, safety practices, and reported outcomes. METHOD: We analyzed NAEC annual report data and results from a supplemental survey specific to EMU practices reported in 2019 from 341 pediatric or adult center directors. Data on staffing, resources, safety practices and complications were collated with epilepsy center characteristics. We summarized using frequency (percentage) for categorical variables and median (inter-quartile range) for continuous variables. We used chi-square or Fisher's exact tests to compare staff responsibilities. RESULTS: The supplemental survey response rate was 100%. Spell classification (39%) and phase 1 testing (28%) were the most common goals of the 91,069 reported admissions. The goal ratio of EEG technologist to beds of 1:4 was the most common during the day (68%) and off-hours (43%). Compared to residents and fellows, advanced practice providers served more roles in the EMU at level 3 or pediatric-only centers. Status epilepticus (SE) was the most common reported complication (1.6% of admissions), while cardiac arrest occurred in 0.1% of admissions. SIGNIFICANCE: EMU staffing and safety practices vary across US epilepsy centers. Reported complications in EMUs are rare but could be further reduced, such as with more effective treatment or prevention of SE. These findings have potential implications for improving EMU safety and quality care.

The effect of alcohol consumption on human physiological and perceptual responses to heat stress: a systematic scoping review.

BACKGROUND: Ethyl alcohol (ethanol) consumption is ostensibly known to increase the risk of morbidity and mortality during hot weather and heatwaves. However, how alcohol independently alters physiological, perceptual, and behavioral responses to heat stress remains poorly understood. Therefore, we conducted a systematic scoping review to understand how alcohol consumption affects thermoregulatory responses to the heat. METHODS: We searched five databases employing the following eligibility criteria, studies must have: 1) involved the oral consumption of ethanol, 2) employed a randomized or crossover-control study design with a control trial consisting of a volume-matched, non-alcoholic beverage, 3) been conducted in healthy adult humans, 4) reported thermophysiological, perceptual, hydration status markers, and/or behavioral outcomes, 5) been published in English, 6) been conducted in air or water at temperatures of > 28°C, 7) involved passive rest or exercise, and 8) been published before October 4th, 2023. RESULTS: After removing duplicates, 7256 titles were screened, 29 papers were assessed for eligibility and 8 papers were included in the final review. Across the 8 studies, there were a total of 93 participants (93 male/0 female), the average time of heat exposure was 70 min and average alcohol dose was 0.68 g·kg1. There were 23 unique outcome variables analyzed from the studies. The physiological marker most influenced by alcohol was core temperature (lowered with alcohol consumption in 3/4 studies). Additionally, skin blood flow was increased with alcohol consumption in the one study that measured it. Typical markers of dehydration, such as increased urine volume (1/3 studies), mass loss (1/3 studies) and decreased plasma volume (0/2 studies) were not consistently observed in these studies, except for in the study with the highest alcohol dose. CONCLUSION: The effect of alcohol consumption on thermoregulatory responses is understudied, and is limited by moderate doses of alcohol consumption, short durations of heat exposure, and only conducted in young-healthy males. Contrary to current heat-health advice, the available literature suggests that alcohol consumption does not seem to impair physiological responses to heat in young healthy males.

Understanding the Effects of Trauma Exposure, Life Stress, Intimate Partner Violence, and Depression on Sexually Transmitted Infection Risk in Post-Conflict Liberia.

In sub-Saharan Africa, sexually transmitted infections (STIs) are a public health concern. The impact of STIs are exacerbated in post-conflict low- and middle-income countries, such as Liberia, where exposure to traumatic events is prevalent and access to mental health services are limited. Following a syndemics framework, this study used regression analyses to explore the independent, additive, and multiplicative effects of four psychosocial conditions (exposure to war-related traumatic events, intimate partner violence [IPV], stressful life events, and depressive symptoms) on self-reported STIs. Data were collected from 379 youth aged 18-30 years (n = 170 women; n = 179 men) in Montserrado County, Liberia. Results revealed that psychosocial variables correlated with each other and STI risk. In multivariable analysis, stressful life events, depressive symptoms, and IPV were statistically significant predictors of STI risk. We found support for an additive effect between the number of psychosocial conditions reported and STI risk, as well as a multiplicative effect (interaction) between IPV and depressive symptoms on STI risk. Our results suggest a synergy between experiencing psychosocial conditions and STI risk and point to the potential benefit of multi-level sexual health approaches that simultaneously address mental health and IPV among youth in Liberia.

Association between state-level medical marijuana legalization and marijuana use during pregnancy: A population-based study.

BACKGROUND AND OBJECTIVES: Despite marijuana's association with adverse pregnancy and birth outcomes, its use during pregnancy increased over the last two decades. During this period, medical marijuana has been legalized in 38 states and the District of Columbia. States with legalized medical marijuana have observed increased marketing of marijuana and related products. This study aims to examine the association between state-level medical marijuana legalization and marijuana use during pregnancy in the United States. METHODS: Using the 2015-2021 National Survey on Drug Use and Health, we evaluated the association between marijuana use in the past month among currently pregnant mothers (N = 4338) and legalized medical marijuana in their state of residence. Survey-weighted descriptive, bivariate, and multivariable logistic regression analyzes were performed. RESULTS: About 5.7% of pregnant women reported using marijuana in the past month, and 59.0% lived in a state where medical marijuana was legalized across 2015-2021. Compared to those living in states without marijuana legalization, more pregnant women living in states with marijuana legalization reported using marijuana (4.6% vs. 6.5%). In the multivariable model, pregnant women residing in states with medical marijuana legalization were more likely to use marijuana than residents of states without legalization (adjusted Odds Ratio: 1.56; 95% Confidence Interval: 1.11-2.18). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: This is the first known study to find that pregnant women living in states where medical marijuana is legalized are more likely to use marijuana during pregnancy. Pregnant women should be informed of adverse pregnancy and birth outcomes linked to marijuana use during pregnancy.

"It's another gay disease": an intersectional qualitative approach contextualizing the lived experiences of young gay, bisexual, and other sexual minoritized men in the United States during the mpox outbreak.

BACKGROUND: The U.S. mpox outbreak in 2022 introduced new and exacerbated existing challenges that disproportionately stigmatize gay, bisexual, and other sexual minoritized men (GBSMM). This study contextualizes the perceptions, susceptibility, and lived experiences of the mpox outbreak among GBSMM in the U.S. using an intersectional framework. METHODS: Between September 2022 to February 2023, we conducted 33 semi-structured qualitative interviews with purposively sampled GBSMM in the Northeast and the South region of the United States on various aspects related to their experience during the mpox outbreak. RESULTS: We identified four themes: (1) understanding and conceptualizations of mpox, (2) mpox vaccine availability and accessibility, (3) mpox vaccine hesitancy and mistrust, and (4) call to action and recommendations. GBSMM collectively discussed the elevated mpox stigmatization and homophobic discourse from mainstream social media and news outlets. GBSMM also discussed the lack of availability of mpox vaccines, unclear procedures to receive the vaccine, and continued mistrust in government, non-government, and other institutions of health that were complicit in anti-LGBTQ + narratives related to mpox. However, they expressed that these challenges may be addressed through more LGTBQ + representation and leveraging ways to empower these communities. CONCLUSION: GBSMM have mpox experiences that are distinct and multifaceted. Effectively addressing mpox and mitigating public health emergencies for GBSMM requires prioritizing destigmatizing communication channels and vaccine distribution strategies by centering their stories and lived experiences to advance health equity.

May Measurement Month 2021: an analysis of blood pressure screening results from a suburban community in the Democratic Republic of the Congo.

Hypertension remains the most powerful contributor to the global morbidity and mortality. May Measurement Month (MMM), a worldwide screening campaign initiated by the International Society of Hypertension (ISH), is organized annually to increase awareness of high blood pressure (BP). We screened 20 913 adult (≥18 years) residents of suburb hamlets of Mbujimayi (mean age 35.1 ± 15.1 years; Black ethnicity: 98.8%; women: 29.6%; diabetes: 1.6%; alcohol drinkers: 16.8% and smokers: 6.7%, previous myocardial infarction: 1.4%; stroke: 0.8%; taking aspirin: 3.2%; taking statins: 1.9%). Three sitting BP readings were taken, and hypertension was defined as a systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg or being on antihypertensive medication. Half of the participants had never had their BP checked, whilst 4.2% of respondents had participated in the MMM19 campaign. 0.9% and 1.7% reported COVID-19 vaccination and positive test, respectively. After multiple imputation of missing BP readings, 14.0% of respondents had hypertension of which 35.8% were aware, 28.0% were on antihypertensive medication and 14.1% had controlled BP. Of those on antihypertensive medication, 40.4% were on monotherapy, 37.2% adhered to taking their medication regularly, and 50.4% had controlled BP (<140/90 mmHg). In regression analyses adjusted for age, sex, and antihypertensive treatment, smoking was associated with lower systolic BP, having more years of education was associated with higher systolic and diastolic BP, and physical activity was associated with lower systolic and diastolic BP. This campaign contributes somewhat to reducing the 'black hole' on the prevalence of hypertension in DRC pending systematic countrywide BP screening.

Short-Term (6 Months or Less) Pain in Cemented versus Cementless Total Knee Arthroplasty: A Systematic Review and Meta-Analysis.

BACKGROUND: Cementless total knee arthroplasty (TKA) has increased in popularity to potentially improve survivorship. Radiostereometric studies demonstrate increased component migration during the first 3 to 6 months in cementless constructs, generating concern for increased postoperative pain during early osseointegration. The purpose of this study was to evaluate short-term (≤ 6 months) pain and function in cemented versus cementless TKA. We hypothesized that cementless TKA patients report increased pain during the short-term (≤ 6 months) postoperative period. METHODS: The MEDLINE, EMBASE, CINAHL, and Cochrane Libraries were searched for studies evaluating short-term (≤ 6 months) outcomes of cemented versus cementless primary TKA. Studies involving hybrid fixation were excluded. A meta-analysis was performed using standardized mean difference for primary outcomes (early postoperative pain) and weighted mean difference (WMD) for secondary outcomes (early postoperative function). RESULTS: There were eleven studies included. There was no significant difference in acute postoperative pain between cemented and cementless TKA within 6 months of index TKA (standardized mean difference 0.08 in favor of cemented TKA; P = .10). Early postoperative forgotten joint scores (WMD 0.81; P = .81) and knee injury and osteoarthritis outcome scores for joint replacement (WMD 0.80 in favor of cemented TKA; P = .14) were also similar between groups. CONCLUSIONS: There is no difference in short-term (≤ 6 months) pain or early function between patients receiving cemented and cementless TKA. This suggests that surgeons may utilize cementless TKA without fear of increased pain due to micromotion within 6 months of index arthroplasty. However, additional studies with uniform assessment methods are needed to further inform differences in short-term pain and early functional outcomes between cemented and cementless TKA.

Tracking animal movements via collaborative acoustic telemetry networks: Multiscale habitat use, phenology, and management insights.

Estuaries support diverse fish and invertebrate communities, including resident species that rely on estuarine habitats year-round and transient migratory species. The unique movement patterns of these animals connect habitats within and far beyond the estuary and are integrally linked to fisheries management objectives. With a focus on Chesapeake Bay, this study leveraged data from collaborative acoustic telemetry networks in the northwest Atlantic to assess habitat use and phenology of movements for seven species of fish (cownose rays, dusky sharks, smooth dogfish, alewife, striped bass, common carp, and blue catfish) and one invertebrate (horseshoe crabs). A total of 288 acoustically tagged individuals were detected >3.2 million times (6,743 to 2,095,717 detections per species) on receivers across ~20.5 degrees of latitude spanning the North American Atlantic seaboard from Florida, USA, to New Brunswick, Canada. Common metrics of movement and phenology grouped these species as resident (common carp, blue catfish, horseshoe crabs), primarily resident in estuaries (juvenile striped bass), and coastal migrant (cownose rays, dusky sharks, smooth dogfish, alewife); maximum distance traveled varied by three orders of magnitude among these species. Further analysis of phenology for coastal migrants elucidated the timing and duration of these species' use of Chesapeake Bay. Collectively, movements linked habitats within Chesapeake Bay and connected the estuary to coastal ecosystems both to the north (e.g., alewife) and south (e.g., cownose rays), creating networks of fisheries management jurisdictions that varied in complexity and identified opportunities for enhancement to current management or co-management of some species. Our results elucidate the importance of estuaries to species with diverse movement behaviors, identify scales and pathways of habitat connectivity via animal movements, and highlight the utility of collaborative acoustic telemetry networks for quantifying movements relevant to both ecological research and fisheries management.

The potential of oviduct tags and fine-scale acoustic telemetry to reveal the timing and location of spawning in Arctic salmonids (Salvelinus spp.).

Identifying and characterizing spawning locations are paramount for the protection of critical fish habitats but can be challenging, particularly in remote locations. Using the underexplored oviduct-tagging technique, we aimed to identify the timing and location of spawning for wild Arctic char (Salvelinus alpinus) and lake trout (Salvelinus namaycush) in two high-Arctic lakes in Nunavut. Specifically, Innovasea V7 acoustic telemetry transmitters were inserted into the oviducts of 13 Arctic char and 4 lake trout, and the timing and location of tag expulsion were determined using a fine-scale positioning system. Twenty Arctic char and 20 lake trout were also tagged with abdominal V16 transmitters, and 10 of them were paired with the oviduct tags, to further study the behavior of individual fish during the spawning season. Oviduct tags from four Arctic char and one lake trout could be used to assess the timing and location of spawning. Spawning anadromous Arctic char drastically reduced their activity and remained proximate to their presumed spawning location immediately before and for months after spawning. In contrast, a non-anadromous (i.e., freshwater resident) Arctic char and a lake trout showed little to no reduction in activity around presumed spawning events. Because of the highlighted sedentary behavior of inferred spawning anadromous Arctic char implanted with both abdominal and oviduct tags, we could also infer potential spawning based on the behavior of individuals equipped only with abdominal tags. Spawning areas identified via telemetry also aligned well with Inuit knowledge of those lakes. This is the first field study to use acoustic oviduct and abdominal tags coupled with a fine-scale positioning system. Despite a limited success rate of ejection, the study reveals the strong potential of the method to study spawning habitat and timing, particularly in remote areas.

Monitoring post-spawning movement, habitat use, and survival of adult anadromous rainbow smelt using acoustic telemetry in a New Hampshire estuary.

Anadromous rainbow smelt (Osmerus mordax, [Mitchill 1814]) are found along the northeast Atlantic coastline of North America, with their range now limited to north of Cape Cod, Massachusetts, USA. Although their anadromous life cycles are described broadly, gaps remain regarding how adult rainbow smelt use estuaries post-spawning, including movement behaviors, habitats used, and specific timing of emigration to coastal waters. In spring 2021, we used acoustic telemetry to characterize movements during and after the spawning season of rainbow smelt captured in tributaries to Great Bay, New Hampshire, USA, a large estuarine system near the southern edge of their range. Forty-four adult rainbow smelt (n = 35 male, n = 9 female) were tagged with Innovasea V5 180-kHz transmitters and an array of 22,180 kHz VR2W receivers were deployed throughout Great Bay to detect movements of tagged fish from March to October 2021. Rainbow smelt were detected 14,186 times on acoustic telemetry receivers, with 41 (93%) of the tagged individuals being detected at least once post-tagging. Individuals were detected moving between tributaries, revealing that rainbow smelt can use multiple rivers during the spawning season (March-April). Mark-recapture Cormack-Jolly-Seber models estimated 83% (95% confidence interval 66%-92%) of rainbow smelt survived to the mainstem Piscataqua River, and a minimum of 50% (22 of 44) reached the seaward-most receivers and were presumed to have survived emigration. Most individuals that survived remained in the estuary for multiple weeks (average = 19.47 ± 1.99 standard error days), displaying extended use of estuarine environments. Downstream movements occurred more frequently during ebb tides and upstream movements with flood tides, possibly a mechanism to reduce energy expenditures. Fish emigrated from the estuary by mid-May to the coastal Gulf of Maine. Our results underscore that rainbow smelt need access to a variety of habitats, including multiple tributaries and high-quality estuarine habitat, to complete their life cycle.

Time-to-event clinical trial designs: Existing evidence and remaining concerns.

Well-designed placebo-controlled clinical trials are critical to the development of novel treatments for epilepsy, but their design has not changed for decades. Patients, clinicians, regulators, and innovators all have concerns that recruiting for trials is challenging, in part, due to the static design of maintaining participants for long periods on add-on placebo when there are an increasing number of options for therapy. A traditional trial maintains participants on blinded treatment for a static period (e.g., 12 weeks of maintenance), during which participants on placebo have an elevated risk of sudden unexpected death in epilepsy compared to patients on an active treatment. Time-to-event trials observe participants on blinded treatment until a key event occurs (e.g., post-randomization seizure count matches pre-randomization monthly seizure count). In this article, we review the evidence for these designs based on re-analysis of prior trials, one published trial that used a time-to-second seizure design, and experience from an ongoing blinded trial. We also discuss remaining concerns regarding time-to-event trials. We conclude that, despite potential limitations, time-to-event trials are a potential promising mechanism to make trials more patient friendly and reduce placebo exposure, which are urgent needs to improve safety and increase recruitment to trials.