Recruitment of a threatened foundation oyster species varies with large and small spatial scales.

Understanding how habitat attributes (e.g., patch area and sizes, connectivity) control recruitment and how this is modified by processes operating at larger spatial scales is fundamental to understanding population sustainability and developing successful long-term restoration strategies for marine foundation species-including for globally threatened reef-forming oysters. In two experiments, we assessed the recruitment and energy reserves of oyster recruits onto remnant reefs of the oyster Saccostrea glomerata in estuaries spanning 550 km of coastline in southeastern Australia. In the first experiment, we determined whether recruitment of oysters to settlement plates in three estuaries was correlated with reef attributes within patches (distances to patch edges and surface elevation), whole-patch attributes (shape and size of patches), and landscape attributes (connectivity). We also determined whether environmental factors (e.g., sedimentation and water temperature) explained the differences among recruitment plates. We also tested whether differences in energy reserves of recruits could explain the differences between two of the estuaries (one high- and one low-sedimentation estuary). In the second experiment, across six estuaries (three with nominally high and three with nominally low sedimentation rates), we tested the hypothesis that, at the estuary scale, recruitment and survival were negatively correlated to sedimentation. Overall, total oyster recruitment varied mostly at the scale of estuaries rather than with reef attributes and was negatively correlated with sedimentation. Percentage recruit survival was, however, similar among estuaries, although energy reserves and condition of recruits were lower at a high- compared to a low-sediment estuary. Within each estuary, total oyster recruitment increased with patch area and decreased with increasing tidal height. Our results showed that differences among estuaries have the largest influence on oyster recruitment and recruit health and this may be explained by environmental processes operating at the same scale. While survival was high across all estuaries, growth and reproduction of oysters on remnant reefs may be affected by sublethal effects on the health of recruits in high-sediment estuaries. Thus, restoration programs should consider lethal and sublethal effects of whole-estuary environmental processes when selecting sites and include environmental mitigation actions to maximize recruitment success.

Attract-and-kill for managing Popillia japonica (Coleoptera: Scarabaeidae) abundance and leaf injury in commercial vineyards.

Popillia japonica Newman (Coleoptera: Scarabaeidae) feeding negatively impacts many plant species, including grapes, potentially reducing fruit quality and yield. Chemical control, representing the current grower standard, relies on frequent broadcast applications of broad-spectrum insecticides, with alternative management strategies mostly lacking. Attract-and-kill (A&K) is a behavioral management strategy that combines semiochemical attractants and a killing agent on a substrate. This study assessed the impact of A&K on (i) the number of P. japonica adults and (ii) the percent of P. japonica feeding injury on grape foliage compared to the grower standard in commercial vineyards. This 2-year study was conducted at 3 commercial vineyards with 4 paired plots consisting of a grower standard control and an A&K treatment. The A&K treatment consisted of commercial lures, each placed on outside-edge grapevines, and weekly applications of carbaryl on the plants holding lures. The grower standard received broadcast insecticide applications at the grower's discretion. The A&K treatment experienced similar numbers of P. japonica adults and similar proportions of leaf injury compared to the grower standard. The use of A&K reduced by 96% the crop area treated with insecticides compared to the grower standard. The area treated by A&K was at the edge of the vineyards, where more leaf injury occurred regardless of treatment. A&K is a targeted approach that was effective at managing P. japonica and reducing chemical inputs on a small scale. It has the potential to be scaled up and refined to provide growers with a new management strategy.

Trisomy 21 Alters Cell Proliferation and Migration of iPSC-Derived Cardiomyocytes on Type VI Collagen.

Purpose: Individuals with Down syndrome (DS) are 2000 times more likely to develop a congenital heart defect (CHD) than the typical population Freeman et al. in Am J Med Genet 80:213-217 (1998). The majority of CHDs in individuals with DS characteristically involve the atrioventricular (AV) canal, including the valves and the atrial or ventricular septum. Type VI collagen (COLVI) is the primary structural component in the developing septa and endocardial cushions, with two of the three genes encoding for COLVI located on human chromosome 21 and upregulated in Down syndrome (von Kaisenberg et al. in Obstet Gynecol 91:319-323, 1998; Gittenberger-De Groot et al. in Anatom Rec Part A 275:1109-1116, 2023). Methods: To investigate the effect of COLVI dosage on cardiomyocytes with trisomy 21, induced pluripotent stem cells (iPSC) from individuals with DS and age- and sex-matched controls were differentiated into cardiomyocytes (iPSC-CM) and plated on varying concentrations of COLVI. Results: Real time quantitative PCR showed decreased expression of cardiac-specific genes of DS iPSC-CM lines compared to control iPSC-CM. As expected, DS iPSC-CM had increased expression of genes on chromosome 21, including COL6A1, COL6A2, as well as genes not located on chromosome 21, namely COL6A3, HAS2 and HYAL2. We found that higher concentrations of COLVI result in decreased proliferation and migration of DS iPSC-CM, but not control iPSC-CM. Conclusions: These results suggest that the increased expression of COLVI in DS may result in lower migration-driven elongation of endocardial cushions stemming from lower cell proliferation and migration, possibly contributing to the high incidence of CHD in the DS population. Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-023-00791-x.

Non-inferiority and Safety of Increased Povidone-Iodine (Betadine) Concentration for Irrigation Following Primary Total Joint Arthroplasty (TJA).

Introduction Diluted Betadine (Purdue Pharma, Stamford, Conn) irrigation following primary total joint arthroplasty (pTJA) may reduce the risk of periprosthetic joint infection (PJI). A recent in vitro study found a minimal inhibitory concentration (MIC) of 0.63% Povidone-iodine (Betadine) for several bacterial isolates. This study reports outcomes of patients undergoing TJA using 0.54% Betadine irrigation compared to a historical cohort using 0.3% Betadine irrigation. Methods A retrospective chart review of patients who underwent pTJA from September 2017 to December 2020. 0.3% Betadine was used in a historical cohort and 0.54% Betadine in the experimental group. Patient demographics, intra-operative data, all-cause revision, and infection data were collected for the three-month post-operative period. Outcome frequencies between groups were compared using Fisher-Exact tests. Results Six hundred sixty-one patients underwent pTJA: 308 total knee arthroplasty (TKA), and 353 total hip arthroplasty (THA). 0.3% Betadine group had seven (3.1%) revisions: five (2.2%) underwent a revision for non-infectious reasons, and two (0.9%) for PJI. 0.54% Betadine group had 11 (2.5%) revisions: nine (2.1%) underwent revision for non-infectious reasons, two (0.4%) for PJI. No significant difference was found for rates of all-cause revision or infection between groups. No adverse intra-operative events occurred with the higher Betadine concentration. Conclusion This study demonstrated no difference in rates of all-cause revision or PJI when using 0.3% Betadine versus 0.54% Betadine for irrigation following pTJA. No adverse intraoperative events occurred with 0.54% Betadine irrigation. Given recent in vitro data supporting increased Betadine MIC, our results showed safety and non-inferiority with respect to three-month post-operative complication rates. Further investigation through a large powered randomized controlled study is needed to determine the optimal Betadine irrigation concentration for PJI prevention is required.

A Comprehensive Review of Solriamfetol to Treat Excessive Daytime Sleepiness.

Purpose of Review: This is a comprehensive review of the literature regarding the use of Solriamfetol for excessive daytime sleepiness. It covers the background and current therapeutic approaches to treating excessive daytime sleepiness, the management of common comorbidities, and the existing evidence investigating the use of Solriamfetol for this purpose. Recent Findings: Excessive daytime sleepiness leads to worse quality of life, a medical sequela and significant economic cost. There are multiple phenotypes of excessive daytime sleepiness depending on the comorbidity making treatment challenging. Due to the complexity of etiology there is not a cure for this ailment. Solriamfetol is a norepinephrine/dopamine dual reuptake antagonist that can be used to manage daytime sleepiness. Solriamfetol was first approved by the FDA in 2018 for use in excessive daytime sleepiness associated with obstructive sleep apnea and narcolepsy. Ongoing literature has proved this drug to be a safe and effective alternative pharmacotherapy. Summary: Recent epidemiological data estimate up to one-third of the general adult population suffers from excessive daytime sleepiness. There is no cure to daytime somnolence and current pharmacotherapeutic regimens have worrisome side effect profiles. Solriamfetol is a new class of drug that offers a safe and effective alternative option for clinical providers treating excessive daytime sleepiness.

A Comprehensive Review of Lemborexant to Treat Insomnia.

Purpose of Review: This is a comprehensive review of the literature regarding Lemborexant for the treatment of insomnia. It covers the background and management of insomnia and then reviews the body of existing evidence evaluating the use of Lemborexant for this purpose. Recent Findings: Insomnia leads to significant decreased in quality of life and economic burden due to decreased workplace performance and increased health care costs. Insomnia manifests as a single common pathway of hyperarousal due to a highly complex network of interactions between activation of the sympathetic system and the endocrine system. Lemborexant is a dual orexin 1/2 antagonist that blocks cortical arousal and promotes sleep state transition. Lemborexant was approved by the FDA in 2019 for use in insomnia. It belongs to a class of orexin neuropeptide inhibitors that is growing in popular clinical application. Summary: Insomnia is a crippling disorder of the sleep wake cycle that drives significant morbidity and mortality in the United States. It carries a high societal and economic toll due to direct and indirect effects to the healthcare system. Lemborexant is a new addition to the orexin antagonist class of drugs that already includes Almorexant and Suvorexant that has superior pharmacokinetic properties. While Lemborexant does have a mild side effect profile, its clinical safety and efficacy make it a promising insomnia drug of the future.

Müllerian-type carcinosarcoma arising in gastric endometriosis: Case report and review of the literature.

Although endometriosis is a common condition, both extrapelvic endometriosis and endometriosis associated malignancy (EAM) are rare. We describe the first reported case of a patient with Müllerian-type carcinosarcoma arising in gastric endometriosis.

Photorefractive Keratectomy in Student Naval Aviators: Outcomes of the U.S. Navy Accessioning Study.

PURPOSE: To present the outcomes of the U.S. Navy photorefractive keratectomy (PRK) accessioning study conducted between 2000 and 2005 that helped lead to the acceptance of laser vision correction within the U.S. aviation industry. METHODS: In this prospective masked study, a total of 301 students who had PRK and underwent naval flight training were compared to 4,368 untreated peers. Three training pipelines were compared: propeller/jet transport, jet fighters, and helicopters. The evaluated metrics were flight and academic performance (assessed for the primary and advanced stage of the training as normalized Navy Standard Score [NSS]), as well as the student attrition rate from training. RESULTS: The attrition rate was lower in the PRK group compared to controls (15.9% vs 23.2%; P = .004). In the primary stage of training, students who had PRK outperformed controls in flight training performance in the propeller/jet transport pipeline (average NSS after PRK: 52.4 ± 7.5 vs controls: 50.7 ± 6.4, P = .02), but the flight performance in the jet fighter and helicopter pipelines was comparable between the two groups. Academic performance in the primary stage of training was approximately 7% to 13% higher in students who had PRK for all training pipelines. During the advanced training stage, there was no difference in the flight performance between the groups in any of the presented pipelines. Academic performance was significantly better for students who had PRK in the helicopter pipeline (51.2 ± 11.0 vs 46.7 ± 11.7 P < .001) but comparable between the two groups in the remaining pipelines. CONCLUSIONS: Refractive surgery did not have adverse effects on flight performance metrics. Pilots who had PRK had comparable or better outcomes than their untreated peers. [J Refract Surg. 2024:40(3):e173-e181.].

Functional EPAS1/HIF2A missense variant is associated with hematocrit in Andean highlanders.

Hypoxia-inducible factor pathway genes are linked to adaptation in both human and nonhuman highland species. EPAS1, a notable target of hypoxia adaptation, is associated with relatively lower hemoglobin concentration in Tibetans. We provide evidence for an association between an adaptive EPAS1 variant (rs570553380) and the same phenotype of relatively low hematocrit in Andean highlanders. This Andean-specific missense variant is present at a modest frequency in Andeans and absent in other human populations and vertebrate species except the coelacanth. CRISPR-base-edited human cells with this variant exhibit shifts in hypoxia-regulated gene expression, while metabolomic analyses reveal both genotype and phenotype associations and validation in a lowland population. Although this genocopy of relatively lower hematocrit in Andean highlanders parallels well-replicated findings in Tibetans, it likely involves distinct pathway responses based on a protein-coding versus noncoding variants, respectively. These findings illuminate how unique variants at EPAS1 contribute to the same phenotype in Tibetans and a subset of Andean highlanders despite distinct evolutionary trajectories.

Systematic review of the patient burden of generalised myasthenia gravis in Europe, the Middle East, and Africa.

BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune disease characterised by muscle weakness, and progression from ocular (oMG) to generalised (gMG) symptoms results in a substantial negative impact on quality of life (QoL). This systematic review aimed to provide an overview of the patient burden experienced by people living with gMG. METHODS: Electronic database searches (conducted March 2022), supplemented by interrogation of grey literature, were conducted to identify studies reporting patient burden outcomes in patients with gMG in Europe, the Middle East and Africa. Results were synthesised narratively due to the heterogeneity across trials. RESULTS: In total, 39 patient burden publications (representing 38 unique studies) were identified as relevant for inclusion in the systematic review, consisting of 37 publications reporting formal patient-reported outcome measures (PROMs), and two publications describing alternative qualitative assessments of patient experience. The studies included a variety of measures including generic and disease-specific PROMs, as well as symptom-specific PROMs focusing on key comorbidities including depression, anxiety, fatigue and sleep disturbance. The findings showed some variation across studies and PROMs; however, in general there was evidence for worse QoL in patients with gMG than in healthy controls or in patients with oMG, and a trend for worsening QoL with increasing MG severity. CONCLUSIONS: This review highlights the importance of considering patient QoL when developing and assessing treatment and management plans for patients with gMG. However, the heterogeneity identified across studies illustrates the need for further representative and well-powered studies in large cohorts administering consistent, validated questionnaires. TRIAL REGISTRATION: The protocol for this systematic review was registered in PROSPERO: CRD42022328444.

Data-driven decomposition of crowd noise from indoor sporting events.

Separating crowd responses from raw acoustic signals at sporting events is challenging because recordings contain complex combinations of acoustic sources, including crowd noise, music, individual voices, and public address (PA) systems. This paper presents a data-driven decomposition of recordings of 30 collegiate sporting events. The decomposition uses machine-learning methods to find three principal spectral shapes that separate various acoustic sources. First, the distributions of recorded one-half-second equivalent continuous sound levels from men's and women's basketball and volleyball games are analyzed with regard to crowd size and venue. Using 24 one-third-octave bands between 50 Hz and 10 kHz, spectrograms from each type of game are then analyzed. Based on principal component analysis, 87.5% of the spectral variation in the signals can be represented with three principal components, regardless of sport, venue, or crowd composition. Using the resulting three-dimensional component coefficient representation, a Gaussian mixture model clustering analysis finds nine different clusters. These clusters separate audibly distinct signals and represent various combinations of acoustic sources, including crowd noise, music, individual voices, and the PA system.

Effects of a high cholesterol diet on chill tolerance are highly context-dependent in Drosophila.

Chill susceptible insects are thought to be injured through different mechanisms depending on the duration and severity of chilling. While chronic chilling causes "indirect" injury through disruption of metabolic and ion homeostasis, acute chilling is suspected to cause "direct" injury, in part through phase transitions of cell membrane lipids. Dietary supplementation of cholesterol can reduce acute chilling injury in Drosophila melanogaster (Shreve et al., 2007), but the generality of this effect and the mechanisms underlying it remain unclear. To better understand how and why cholesterol has this effect, we assessed how a high cholesterol diet and thermal acclimation independently and interactively impact several measures of chill tolerance. Cholesterol supplementation positively affected tolerance to acute chilling in warm-acclimated flies (as reported previously). Conversely, feeding on the high-cholesterol diet negatively affected tolerance to chronic chilling in both cold and warm acclimated flies, as well as tolerance to acute chilling in cold acclimated flies. Cholesterol had no effect on the ability of flies to remain active in the cold or recover movement after a cold stress. Our findings support the idea that dietary cholesterol reduces mechanical injury to membranes caused by direct chilling injury, and that acute and chronic chilling are associated with distinct mechanisms of injury. Feeding on a high-cholesterol diet may interfere with mechanisms involved in cold acclimation, leaving cholesterol augmented flies more susceptible to chilling injury under some conditions.

Tubular mitochondrial pyruvate carrier disruption elicits redox adaptations that protect from acute kidney injury.

OBJECTIVE: Energy-intensive kidney reabsorption processes essential for normal whole-body function are maintained by tubular epithelial cell metabolism. Although tubular metabolism changes markedly following acute kidney injury (AKI), it remains unclear which metabolic alterations are beneficial or detrimental. By analyzing large-scale, publicly available datasets, we observed that AKI consistently leads to downregulation of the mitochondrial pyruvate carrier (MPC). This investigation aimed to understand the contribution of the tubular MPC to kidney function, metabolism, and acute injury severity. METHODS: We generated tubular epithelial cell-specific Mpc1 knockout (MPC TubKO) mice and employed renal function tests, in vivo renal 13C-glucose tracing, mechanistic enzyme activity assays, and tests of injury and survival in an established rhabdomyolysis model of AKI. RESULTS: MPC TubKO mice retained normal kidney function, displayed unchanged markers of kidney injury, but exhibited coordinately increased enzyme activities of the pentose phosphate pathway and the glutathione and thioredoxin oxidant defense systems. Following rhabdomyolysis-induced AKI, compared to WT control mice, MPC TubKO mice showed increased glycolysis, decreased kidney injury and oxidative stress markers, and strikingly increased survival. CONCLUSIONS: Our findings suggest that decreased renal tubular mitochondrial pyruvate uptake hormetically upregulates oxidant defense systems before AKI and is a beneficial adaptive response after rhabdomyolysis-induced AKI. This raises the possibility of therapeutically modulating the MPC to attenuate AKI severity.

PDGFRß Signaling Cooperates with ß-Catenin to Modulate c-Abl and Biologic Behavior of Desmoid-Type Fibromatosis.

PURPOSE: This study sought to identify ß-catenin targets that regulate desmoid oncogenesis and determine whether external signaling pathways, particularly those inhibited by sorafenib (e.g., PDGFRß), affect these targets to alter natural history or treatment response in patients. EXPERIMENTAL DESIGN: In vitro experiments utilized primary desmoid cell lines to examine regulation of ß-catenin targets. Relevance of results was assessed in vivo using Alliance trial A091105 correlative biopsies. RESULTS: CTNNB1 knockdown inhibited hypoxia-regulated gene expression in vitro and reduced levels of HIF1α protein. ChIP-seq identified ABL1 as a ß-catenin transcriptional target that modulated HIF1α and desmoid cell proliferation. Abrogation of either CTNNB1 or HIF1A inhibited desmoid cell-induced VEGFR2 phosphorylation and tube formation in endothelial cell co-cultures. Sorafenib inhibited this activity directly but also reduced HIF1α protein expression and c-Abl activity while inhibiting PDGFRß signaling in desmoid cells. Conversely, c-Abl activity and desmoid cell proliferation were positively regulated by PDGF-BB. Reduction in PDGFRß and c-Abl phosphorylation was commonly observed in biopsy samples from patients after treatment with sorafenib; markers of PDGFRß/c-Abl pathway activation in baseline samples were associated with tumor progression in patients on the placebo arm and response to sorafenib in patients receiving treatment. CONCLUSIONS: The ß-catenin transcriptional target ABL1 is necessary for proliferation and maintenance of HIF1α in desmoid cells. Regulation of c-Abl activity by PDGF signaling and targeted therapies modulates desmoid cell proliferation, thereby suggesting a reason for variable biologic behavior between tumors, a mechanism for sorafenib activity in desmoids, and markers predictive of outcome in patients.

Radiological analysis and outcomes of isolated greater tuberosity fracture-dislocations.

BACKGROUND: The purpose of this study was to investigate different radiological characteristics for isolated greater tuberosity (GT) fracture-dislocations and their effects on complication and reoperation rates. METHODS: A two-centre, retrospective study was performed on patients with a minimum 1-year follow-up (median 4.5 years). Patients were split into two groups, Group A (<65 years old) and Group B (≥65 years old). Outcomes included initial injury characteristics (dislocation and fracture type, AC/BC ratio and distances), the reduction environment and postreduction outcomes including complications. RESULTS: A total of 55 patients were included in this study, with a reduction in the emergency department (ED) performed in 93% of patients. Complication rates (47% overall) were similar in both groups, with an overall nonunion rate of 27%. No nonunions occurred in fractures reduced in theatre compared with 29% occurring in reductions in ED (p<0.001); 11% of patients experienced surgical neck fractures, the majority of which were in Group B (p=0.003). A larger fracture fragment (i.e. higher AC/BC or AC distances) was correlated with a higher incidence of nonunion in Group B compared with Group A (p=0.003), and a higher risk of stiffness in both groups (p=0.049); 16% of patients demonstrated delayed displacement of their GT. CONCLUSIONS: This study highlights the high complication rates associated with these injuries. Age and specific radiological parameters should be taken into consideration when risk stratifying, as should reducing these fractures in a theatre setting. Interval radiographs are also advised to monitor GT displacement for at least 2-3 weeks.

Higher glucose and insulin responses to a mixed meal are associated with increased risk of diabetic retinopathy in Indigenous Americans.

PURPOSE: Prior research has focused on glucose/insulin responses to meal challenges to create personalized diets to improve health, though it is unclear if these responses predict chronic diseases. We aimed to identify glucose and insulin responses to a mixed meal tolerance test (MMTT) that predict the development of diabetic retinopathy (DR) and compare the predictive abilities with the oral glucose tolerance test (OGTT). METHODS: Indigenous American adults without diabetes (n = 168) underwent a 4-h MMTT, body composition assessment, and a 3-h OGTT at baseline. During follow-up (median 13.4 years), DR was diagnosed by direct ophthalmoscopy (n = 28) after onset of type 2 diabetes. Total and incremental area under the curve (AUC and iAUC) were calculated from glucose/insulin responses after the MMTT and OGTT. RESULTS: In separate Cox proportional hazards models adjusted for age, sex, and body fat (%), MMTT glucose AUCs (180-min and 240-min) and iAUC (180-min) predicted DR (HR 1.50, 95% CI 1.06, 2.12; HR 1.50, 95% CI 1.05, 2.14; HR 1.58, 95% CI 1.01, 2.46). The predictive abilities were better than the fasting OGTT glucose (p < 0.01) but similar to the 120-min OGTT glucose (p = 0.53). MMTT insulin AUCs (180-min and 240-min) and iAUC (180-min) also predicted DR (HR 1.65, 95% CI 1.09, 2.51; HR 1.58, 95% CI 1.00, 2.35; HR 1.53 95% CI 1.06, 2.22) while insulin AUC and iAUC from the OGTT did not (p > 0.05). CONCLUSIONS: Higher MMTT glucose and insulin responses predicted DR and were comparable to the OGTT, supporting the use of a meal challenge for precision nutrition. TRIAL REGISTRATIONS: Clinical Trial Registry: ClinicalTrials.gov identifier: NCT00340132, NCT00339482.

Mercury concentrations and export from small central Canadian boreal forest catchments before, during, and after forest harvest.

Northern boreal forests are a strong sink for mercury (Hg), a global contaminant of significant concern to wildlife and human health. Mercury stored in forest soils can be mobilized via runoff and erosion, and under suitable conditions can be methylated to its much more bioaccumulative form, methylmercury. Forest harvesting can affect the mobilization and methylation of Hg, though the direction and magnitude of the impact is unclear or conflicting across previous studies. This study examined 5 harvested and 2 reference watersheds in northwestern Ontario, Canada, before, during, and after harvest to quantify changes in stream total and methylmercury concentration and loads and identified potential landscape and management factors that contribute to differences in stream response. In watersheds where streams were buffered by natural vegetation (≥30 m), no significant changes in total Hg or methylmercury concentrations or loads were observed. Significant increases in methylmercury concentrations and loads were observed downstream of a stream crossing in a watershed where the relatively small stream was unmapped and therefore only buffered by a 3 m machine exclusion zone. These results show that when current best management practices that minimize soil and water disturbance are followed, harvest can have a minimal impact on total and methylmercury loads, even in extensively harvested watersheds. However, there is a need for improved mapping of small streams to ensure best management practices are applied adequately across the landscape.