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Aluminum hydroxide polymorphs are of widespread importance yet their kinetics of nucleation and growth remain beyond the reach of current models. Here we attempt to unveil the reaction processes underlying the polymorphs formation at high chemical potential. We examine their formation in-situ from supersaturated alkaline sodium aluminate solutions using deuteration and time-resolved neutron pair distribution function analyses, which indicate the formation of individual Al(OD)3 layers as an intermediate particle phase. These layers ultimately stack to form gibbsite- or bayerite-like layered heterostructures. Ex-situ characterization of the recovered precipitates using 27Al magic angle spinning nuclear magnetic resonance spectroscopy, Raman, X-ray diffraction, and scanning electron microscopy, suggests the presence of additional intermediate states, an amorphous compound bearing both tetrahededrally- and penta-coordinated Al3+. These observations reveal the complex pathways to form Al(OD)3 monolayers via either transient pentacoordinate species or amorphous-to-ordered transitions. The subsequent crystallization of admixed gibbsite/bayerite is followed by an Al(OD)3 monolayer attachment process.
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The connection between solution structure, particle forces, and emergent phenomena at solid-liquid interfaces remains ambiguous. In this case study on boehmite aggregation, we established a connection between interfacial solution structure, emerging hydration forces between two approaching particles, and the resulting structure and kinetics of particle aggregation. In contrast to expectations from continuum-based theories, we observed a nonmonotonic dependence of the aggregation rate on the concentration of sodium chloride, nitrate, or nitrite, decreasing by 15-fold in 4 molal compared to 1 molal solutions. These results are accompanied by an increase in repulsive hydration forces and interfacial oscillatory features from 0.27-0.31 nm in 0.01 molal to 0.38-0.52 nm in 2 molal. Moreover, molecular dynamics (MD) simulations indicated that these changes correspond to enhanced ion correlations near the interface and produced loosely bound aggregates that retain electrolyte between the particles. We anticipate that these results will enable the prediction of particle aggregation, attachment, and assembly, with broad relevance to interfacial phenomena.
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In Staphylococcus aureus infections in men eligible for doxycycline post-exposure prophylaxis (doxy-PEP), tetracycline non-susceptibility is more prevalent than in the overall population and is associated with resistance to trimethoprim-sulfamethoxazole and clindamycin. Doxy-PEP may select for S. aureus multi-drug resistance, underscoring the importance of surveillance.
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Background: Coronary plaque is common among people with HIV (PWH) with low-to-moderate traditional atherosclerotic cardiovascular disease (ASCVD) risk. Objectives: The purpose of this study was to determine the association of high-sensitivity cardiac troponin T (hs-cTnT) levels with coronary plaque characteristics and evaluate if hs-cTnT improves identification of these features beyond traditional ASCVD risk factors among PWH. Methods: Among PWH receiving stable antiretroviral therapy with low-to-moderate ASCVD risk and no known history of ASCVD, hs-cTnT levels and measures of plaque by coronary computed tomography angiography were assessed. Primary outcomes included the association of hs-cTnT level with the presence of any plaque, vulnerable plaque, coronary artery calcium (CAC) score, and Leaman score. Assessment of model discrimination of hs-cTnT for plaque characteristics was also performed. Results: The cohort included 708 U.S. participants with a mean age of 51 ± 6 years, 119 (17%) females, a median ASCVD risk score of 4.4% (Q1-Q3: 2.5%-6.6%), and a median hs-cTnT level of 6.7 ng/L (detectable level ≥6 ng/L in 61%). Any plaque was present in 341 (48%), vulnerable plaque in 155 (22%), CAC>100 in 68 (10%), and a Leaman score >5 in 105 (15%). After adjustment for ASCVD risk score, participants with hs-cTnT >9.6 ng/L (highest category) versus an undetectable level (<6 ng/L) had a greater relative risk for any plaque (1.37, 95% CI: 1.12-1.67), vulnerable plaque (1.47, 95% CI: 1.16-1.87), CAC>100 (2.58, 95% CI: 1.37-4.83), and Leaman score >5 (2.13, 95% CI: 1.32-3.46). The addition of hs-cTnT level modestly improved the discrimination of ASCVD risk score to identify critical plaque features. Conclusions: In PWH without known ASCVD, hs-cTnT levels were strongly associated with and improved prediction of subclinical coronary plaque. (Evaluating the Use of Pitavastatin to Reduce the Risk of Cardiovascular Disease in HIV-Infected Adults [REPRIEVE]; NCT02344290).
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Importance: Obesity is associated with numerous psychosocial complications, making psychiatric safety a consideration for treating people with obesity. Few studies have investigated the psychiatric safety of newly available antiobesity medications. Objective: To evaluate the psychiatric safety of subcutaneous semaglutide, 2.4 mg, once weekly in people without known major psychopathology. Design, Setting, and Participants: This post hoc analysis of pooled data from the randomized, double-blind, placebo-controlled, multicenter phase 3a STEP 1, 2, and 3 trials (68 weeks; 2018-2020) and phase 3b STEP 5 trial (104 weeks; 2018-2021) included adults with overweight or obesity; STEP 2 participants also had type 2 diabetes. Trial designs have been published previously. Interventions: Semaglutide, 2.4 mg, vs placebo. Main Outcomes and Measures: Depressive symptoms and suicidal ideation/behavior were assessed using the Patient Health Questionnaire (PHQ-9) and Columbia-Suicide Severity Rating Scale, respectively. Psychiatric and nervous system disorder adverse events were investigated. Results: This analysis included 3377 participants in the STEP 1, 2, and 3 trials (2360 women [69.6%]; mean [SD] age, 49 [13] years) and 304 participants in STEP 5 (236 women [77.6%]; mean [SD] age, 47 [11] years). In the STEP 1, 2, and 3 trials, mean (SD) baseline PHQ-9 scores for the semaglutide, 2.4 mg, and placebo groups were 2.0 (2.3) and 1.8 (2.3), respectively, indicating no/minimal symptoms of depression. PHQ-9 scores at week 68 were 2.0 (2.9) and 2.4 (3.3), respectively; the estimated treatment difference (95% CI) between groups was -0.56 (-0.81 to -0.32) (P < .001). Participants treated with semaglutide vs placebo were less likely to shift (from baseline to week 68) to a more severe category of PHQ-9 depression (odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001). Based on the Columbia-Suicide Severity Rating Scale, 1% or fewer of participants reported suicidal ideation/behavior during treatment, with no differences between semaglutide, 2.4 mg, and placebo. Psychiatric disorder adverse events were generally balanced between groups. Similar results were observed in STEP 5. Conclusions and Relevance: The results of this post hoc analysis suggest that treatment with semaglutide, 2.4 mg, did not increase the risk of developing symptoms of depression or suicidal ideation/behavior vs placebo and was associated with a small but statistically significant reduction in depressive symptoms (not considered clinically meaningful). People with obesity should be monitored for mental health concerns so they can receive appropriate support and care. Trial Registration: ClinicalTrials.gov Identifiers: STEP 1 (NCT03548935), 2 (NCT03552757), 3 (NCT03611582), and 5 (NCT03693430).
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BACKGROUND: Noise-induced hearing loss (NIHL) is a serious concern for orthopedic surgeons. The National Institute for Occupational Safety and Health (NIOSH) sets the safe exposure limit at 85 dB for 8 hours, yet operating rooms often surpass this limit. This study investigated if using an automated broaching system exposes orthopedic surgeons to dangerous decibel (dB) levels. MATERIALS AND METHODS: A prospective study analyzed 138 intraoperative sound recordings from 92 total hip arthroplasty (THA) surgeries and 46 baseline measurements at an academic-affiliated private practice, using the NIOSH Sound Level Meter (SLM) application and a microphone. The surgeries were categorized into manual and automated broaching. Key metrics measured included maximal dB level (MDL), peak sound pressure (LCpeak), average continuous sound (LAeq), and average weighted sound in an 8-hour period (TWA), along with dose representations, to identify hazardous noise levels. RESULTS: Of the 92 THA sound recordings, 50 used manual broaching and 42 employed automated broaching. Automated broaching exhibited higher noise levels, with an average MDL of 109.92 dBA, a LAeq of 86.09 dBA, a TWA of 76.48 dBA, and a projected noise dose of 137.74%. In contrast, manual broaching exhibited an average MDL of 105.87 dBA, a LAeq of 83.06 dBA, a TWA of 72.82 dBA, and a projected noise dose of 82.02%. CONCLUSION: This study highlights the auditory risks from automated broach and manual THA surgeries that orthopedic surgeons experience. Manufacturers should focus on reducing instrument noise when designing surgical tools and orthopedic surgeons and operating room staff should take measures to protect themselves from NIHL during surgery. [Orthopedics. 202x;4x(x):xx-xx.].
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Interim results from two phase 1 trials demonstrate progress in the use of chimeric antigen receptor (CAR) T cell therapy for recurrent glioblastoma (GBM).
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Glioblastoma , Receptores Quiméricos de Antígenos , Linfocitos T , Glioblastoma/terapia , Glioblastoma/inmunología , Humanos , Receptores Quiméricos de Antígenos/inmunología , Linfocitos T/inmunología , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/inmunología , Inmunoterapia Adoptiva/métodos , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores de Antígenos de Linfocitos T/inmunologíaRESUMEN
Monitoring forest canopies is vital for ecological studies, particularly for assessing epiphytes in rain forest ecosystems. Traditional methods for studying epiphytes, such as climbing trees and building observation structures, are labor, cost intensive and risky. Unmanned Aerial Vehicles (UAVs) have emerged as a valuable tool in this domain, offering botanists a safer and more cost-effective means to collect data. This study leverages AI-assisted techniques to enhance the identification and mapping of epiphytes using UAV imagery. The primary objective of this research is to evaluate the effectiveness of AI-assisted methods compared to traditional approaches in segmenting/identifying epiphytes from UAV images collected in a reserve forest in Costa Rica. Specifically, the study investigates whether Deep Learning (DL) models can accurately identify epiphytes during complex backgrounds, even with a limited dataset of varying image quality. Systematically, this study compares three traditional image segmentation methods Auto Cluster, Watershed, and Level Set with two DL-based segmentation networks: the UNet and the Vision Transformer-based TransUNet. Results obtained from this study indicate that traditional methods struggle with the complexity of vegetation backgrounds and variability in target characteristics. Epiphyte identification results were quantitatively evaluated using the Jaccard score. Among traditional methods, Watershed scored 0.10, Auto Cluster 0.13, and Level Set failed to identify the target. In contrast, AI-assisted models performed better, with UNet scoring 0.60 and TransUNet 0.65. These results highlight the potential of DL approaches to improve the accuracy and efficiency of epiphyte identification and mapping, advancing ecological research and conservation.
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Dispositivos Aéreos No Tripulados , Costa Rica , Ecosistema , Monitoreo del Ambiente/métodos , Aprendizaje Profundo , Inteligencia Artificial , Bosques , Plantas , Bosque Lluvioso , ÁrbolesRESUMEN
BACKGROUND: Patients being evaluated for revision total joint arthroplasty (RTJA) are often referred to tertiary care centers, which may decrease their access to adequate health care and overburden these health care systems. The purpose of this study was to evaluate the feasibility and effectiveness of RTJA patient evaluation via telehealth. MATERIALS AND METHODS: We identified a consecutive series of patients newly evaluated for a symptomatic TJA by two academic surgeons during a 1-year period. Clinical records, radiographs, and laboratory values were reviewed to determine whether the patient was indicated for RTJA. Efficiency was determined by calculating the percentage of patients who could have been adequately evaluated with telehealth. We then used the modalities required for diagnosis in each RTJA case to determine the feasibility of evaluating such patients through telehealth. RESULTS: Of the 381 patients evaluated for RTJA candidacy, 154 (40.4%) were indicated for revision surgery. All 152 patients evaluated for possible hip revision could have been evaluated and diagnosed via telehealth, demonstrating a telehealth efficiency of 100%. Of 229 patients evaluated for possible knee revision, 183 were able to be evaluated and diagnosed via telehealth. The 46 remaining patients were indicated for revision secondary to instability, which would require an in-office examination for diagnosis. The efficiency of telehealth for potential knee revision patients was 79.9%. CONCLUSION: Telehealth may be useful in evaluating patients with symptomatic TJA. It may increase the efficiency of in-office evaluations and reduce potential barriers to health care access. [Orthopedics. 202x;4x(x):xx-xx.].
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Targeted protein degradation (TPD) is a therapeutic approach that leverages the cell's natural machinery to degrade targets instead of inhibiting them. This is accomplished by using mono- or bifunctional small molecules designed to induce the proximity of target proteins and E3 ubiquitin ligases, leading to ubiquitination and subsequent proteasome-dependent degradation of the target. One of the most significant attributes of the TPD approach is its proposed catalytic mechanism of action, which permits substoichiometric exposure to achieve the desired pharmacological effects. However, apart from one in vitro study, studies supporting the catalytic mechanism of degraders are largely inferred based on potency. A more comprehensive understanding of the degrader catalytic mechanism of action can help aspects of compound development. To address this knowledge gap, we developed a workflow for the quantitative measurement of the catalytic rate of degraders in cells. Comparing a selective and promiscuous BTK degrader, we demonstrate that both compounds function as efficient catalysts of BTK degradation, with the promiscuous degrader exhibiting faster rates due to its ability to induce more favorable ternary complexes. By leveraging computational modeling, we show that the catalytic rate is highly dynamic as the target is depleted from cells. Further investigation of the promiscuous kinase degrader revealed that the catalytic rate is a better predictor of optimal degrader activity toward a specific target compared to degradation magnitude alone. In summary, we present a versatile method for mapping the catalytic activity of any degrader for TPD in cells.
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Proteolisis , Humanos , Agammaglobulinemia Tirosina Quinasa/metabolismo , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación , Complejo de la Endopetidasa Proteasomal/metabolismoRESUMEN
In biogeochemical phosphorus cycling, iron oxide minerals are acknowledged as strong adsorbents of inorganic and organic phosphorus. Dephosphorylation of organic phosphorus is attributed only to biological processes, but iron oxides could also catalyze this reaction. Evidence of this abiotic catalysis has relied on monitoring products in solution, thereby ignoring iron oxides as both catalysts and adsorbents. Here we apply high-resolution mass spectrometry and X-ray absorption spectroscopy to characterize dissolved and particulate phosphorus species, respectively. In soil and sediment samples reacted with ribonucleotides, we uncover the abiotic production of particulate inorganic phosphate associated specifically with iron oxides. Reactions of various organic phosphorus compounds with the different minerals identified in the environmental samples reveal up to ten-fold greater catalytic reactivities with iron oxides than with silicate and aluminosilicate minerals. Importantly, accounting for inorganic phosphate both in solution and mineral-bound, the dephosphorylarion rates of iron oxides were within reported enzymatic rates in soils. Our findings thus imply a missing abiotic axiom for organic phosphorus mineralization in phosphorus cycling.
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BACKGROUND: Patients undergoing total joint arthroplasty (TJA) may receive unexpected medical bills. Such "surprise" bills may cause financial hardship for patients, which prompted policymakers to pass the No Surprises Act. The purpose of this study was to determine the incidence of surprise bills for patients undergoing TJA and the effect of surprise billing on patient satisfaction. MATERIALS AND METHODS: This was a retrospective study of patients who underwent a primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) at a large multi-state institution. Patients completed a questionnaire regarding the incidence of surprise bills after their surgery, details of those bills, and how the bills affected their surgical satisfaction. Independent predictors for receiving a surprise bill were assessed through a multivariate regression analysis. RESULTS: Twelve percent of participants received at least one surprise bill after their TJA. The most common surprise bill came from the surgical facility (48%), followed by anesthesia (36%). Multivariate logistic regression analysis identified older age and Black race to be independent predictors of surprise billing. Furthermore, surgery occurring after the No Surprises Act bill enforcement on January 1, 2022, was found to increase a patient's likelihood of receiving a surprise bill (P=.039, effect size=0.18). Patients who received a surprise bill reported being significantly less satisfied with their surgery (P=.002, effect size=0.45). Forty-nine percent of patients with a surprise bill felt their billing negatively affected their surgical satisfaction. CONCLUSION: Surprise billing continues to occur after TJA and can negatively affect patient satisfaction. Although surgeons may be unable to limit the amount of bills patients receive postoperatively, increased communication and education regarding the perioperative billing process may prove to be beneficial for both patient satisfaction and the physician-patient relationship. [Orthopedics. 2024;47(5):283-288.].
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Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Satisfacción del Paciente , Humanos , Satisfacción del Paciente/estadística & datos numéricos , Masculino , Femenino , Estudios Retrospectivos , Artroplastia de Reemplazo de Cadera/economía , Persona de Mediana Edad , Anciano , Artroplastia de Reemplazo de Rodilla/economía , Encuestas y CuestionariosRESUMEN
Melioidosis is a potentially severe disease caused by the gram-negative soil-dwelling bacterium called Burkholderia pseudomallei. The true breadth of the distribution of this tropical pathogen is starting to emerge with environmental and clinical isolates frequently characterized in new countries and regions. Even so, isolates, clinical cases, and genetic data from the continent of Africa remain scant. We previously confirmed the presence of B. pseudomallei in the environment of Ghana, unmasking a new area of endemicity for this pathogen. Here, we describe the genetic characteristics of isolates obtained from that environmental survey. Twenty-one isolates were subjected to whole genome sequencing and found to represent three discrete sequence types (ST), one of which was novel, and designated ST2058. Phylogenetic analysis places this novel isolate within a B. pseudomallei clade that includes genomes derived from the Americas, although it is closely related to a sub-clade that includes isolates from Africa. Importantly, phenotypic characterization demonstrates common features including API 20NE profiles and B. pseudomallei CPS to support existing diagnostics, and susceptibility to standard of care antibiotics often used in the clinical management of melioidosis. These findings add to our knowledge about the presence and distribution of B. pseudomallei in Africa and represent the first published genomes out of Ghana.
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Surveillance of triatomines or kissing bugs (Hemiptera: Reduviidae: Triatominae), the insect vectors of Trypanosoma cruzi, a Chagas disease agent, is hindered by the lack of an effective trap. To develop a kissing bug trap, we made iterative improvements over 3 years on a basic design resulting in 7 trap prototypes deployed across field sites in Texas, United States and Northern Mexico, yielding the capture of 325 triatomines of 4 species (Triatoma gerstaeckeri [Stål], T. sanguisuga [LeConte], T. neotomae [Neiva], and T. rubida [Uhler]). We began in 2019 with vertical transparent tarpaulin panel traps illuminated with artificial light powered by AC current, which were successful in autonomous trapping of flying triatomines, but were expensive, labor-intensive, and fragile. In 2020, we switched to white LED lights powered by a solar cell. We tested a scaled-down version of the vertical panel traps, a commercial cross-vane trap, and a multiple-funnel trap. The multiple-funnel traps captured 2.6× more kissing bugs per trap-day than cross-vane traps and approached the performance of the vertical panel traps in number of triatomines captured, number of triatomines per trap-day and triatomines per arthropod bycatch. Multiple-funnel traps required the least labor, were more durable, and had the highest triatomines per day per cost. Propylene glycol in the collection cups effectively preserved captured triatomines allowing for molecular detection of T. cruzi. The trapping experiments established dispersal patterns for the captured species. We conclude that multiple-funnel traps with solar-powered LED lights should be considered for adoption as surveillance and potentially mass-trapping management tools for triatomines.
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Circular RNAs are a novel class of RNA transcripts, which regulate important cellular functions in health and disease. Herein, we report on the functional relevance of the circPCMTD1 transcript in acute leukemias. In screening experiments, we found that circPCMTD1 depletion strongly inhibited the proliferative capacity of leukemic cells with BCR-ABL translocations. Mass cytometry experiments identified the aberrant activation of the DNA damage response as an early downstream event of circPCMTD1 depletion. In in vivo experiments, circPCMTD1 targeting prolonged the survival of mice engrafted with leukemic blasts harboring the Philadelphia chromosome. Mechanistically, we found that circPCMTD1 was enriched in the cytoplasm and associated with the ribosomes of the leukemic cells. We detected a cryptic open reading frame within the circPCMTD1 sequence and found that circPCMTD1 could generate a peptide product. The circPCMTD 1-derived peptide interacted with proteins of the BTR complex and enhanced BTR complex formation, thereby increasing tolerance to genotoxic stress.