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1.
Artigo em Inglês | MEDLINE | ID: mdl-38722914

RESUMO

INTRODUCTION: Anatomic and reverse total shoulder arthroplasties (TSAs) are effective treatment options for end-stage glenohumeral osteoarthritis. Those undergoing TSA may also have fibromyalgia, a musculoskeletal condition. However, the association of fibromyalgia with shorter and longer term outcomes after TSA has not been well characterized. METHODS: Patients undergoing TSA for osteoarthritis indications were identified in the PearlDiver M165 database from January 2016 to October 2022. Exclusion criteria included age younger than 18 years, shoulder infection, neoplasm, or trauma within 90 days before surgery, and inactivity in the database within 90 days of surgery. Patients with fibromyalgia were matched in a 1:4 ratio to patients without based on age, sex, and Elixhauser Comorbidity Index. Ninety-day adverse events were compared using univariable and multivariable analyses. Five-year revision-free survival was compared using the log-rank test. RESULTS: Of 163,565 TSA patients, fibromyalgia was identified for 9,035 (5.52%). After matching, cohorts of 30,770 non-fibromyalgia patients and 7,738 patients with fibromyalgia were identified. Multivariable analyses demonstrated patients with fibromyalgia were at independently increased odds ratios (ORs) for the following 90-day complications (decreasing OR order): urinary tract infection (OR = 4.49), wound dehiscence (OR = 3.63), pneumonia (OR = 3.46), emergency department visit (OR = 3.45), sepsis (OR = 3.15), surgical site infection (OR = 2.82), cardiac events (OR = 2.72), acute kidney injury (OR = 2.65), deep vein thrombosis (OR = 2.48), hematoma (OR = 2.03), and pulmonary embolism (OR = 2.01) (P < 0.05 for each). These individual complications contributed to the increased odds of aggregated minor adverse events (OR = 3.68), all adverse events (OR = 3.48), and severe adverse events (OR = 2.68) (P < 0.05 for each). No statistically significant difference was observed in 5-year revision-free survival between groups. DISCUSSION: This study found TSA patients with fibromyalgia to be at increased risk of adverse events within 90 days of surgery. Proper surgical planning and patient counseling are crucial to this population. Nonetheless, it was reassuring that those with fibromyalgia had similar 5-year revision-free survival compared with those without.


Assuntos
Artroplastia do Ombro , Fibromialgia , Complicações Pós-Operatórias , Humanos , Feminino , Fibromialgia/complicações , Masculino , Complicações Pós-Operatórias/epidemiologia , Idoso , Pessoa de Meia-Idade , Osteoartrite/cirurgia , Fatores de Risco , Estudos Retrospectivos
2.
Childs Nerv Syst ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578479

RESUMO

PURPOSE: Despite previous research supporting patient safety in sports after craniosynostosis surgery, parental anxiety remains high. This study sought to evaluate the role of healthcare providers in guiding patients and families through the decision-making process. METHODS: Parents of children with repaired craniosynostosis were asked to assess sports involvement and parental decision-making in children ages 6 and older. Questions were framed primarily on 5-point Likert scales. Sport categorizations were made in accordance with the American Academy of Pediatrics. Chi-squared, linear regression, and Pearson correlation tests were used to analyze associations between the questions. RESULTS: Forty-three complete parental responses were recorded. Mean ages at surgery and time of sports entry were 7.93 ± 4.73 months and 4.76 ± 2.14 years, respectively. Eighty-two percent of patients participated in a contact sport. Discussions with the primary surgeon were more impactful on parental decisions about sports participation than those with other healthcare providers (4.04 ± 1.20 vs. 2.69 ± 1.32). Furthermore, children whose parents consulted with the primary surgeon began participating in sports at a younger age (4.0 ± 1.0 vs. 5.8 ± 2.7 years, p = 0.034). The mean comfort level with contact sports (2.8 ± 1.4) was lower than that with limited-contact (3.8 ± 1.1, p = 0.0001) or non-contact (4.4 ± 1.3, p < 0.0001) sports. CONCLUSION: This study underscores the critical role that healthcare professionals, primarily surgeons, have in guiding families through the decision-making process regarding their children's participation in contact sports.

3.
Hand (N Y) ; : 15589447241247247, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654508

RESUMO

BACKGROUND: Prior studies have compared perioperative opioid prescriptions between carpal tunnel release (CTR) performed wide-awake and with traditional anesthetic techniques, but the association of opioid prescriptions with surgical setting has not been fully explored. The current study assessed the association of opioid prescriptions with surgical setting (office or operating room) for wide-awake CTR. METHODS: Patients with open CTR were identified in an administrative claims database (PearlDiver). Exclusion criteria included age less than 18 years, preoperative data less than 6 months, postoperative data less than 1 month, bilateral surgery, concomitant hand surgery, and traditional anesthesia (general anesthesia, sedation, or regional block). Patients were stratified by surgical setting (office or operating room) and matched by age, sex, Elixhauser Comorbidity Index, and geographic region. Prior opioid prescriptions, opioid dependence/abuse, substance use disorder, back/neck pain, generalized anxiety, and major depression were identified. Opioid prescriptions within 7 days before and 30 days after surgery were characterized. RESULTS: Each matched cohort included 5713 patients. Compared with patients with surgery in the operating room, fewer patients with office-based surgery filled opioid prescriptions (45% vs 62%), and those prescriptions had lower morphine milligram equivalents (MMEs, median 130 vs 188). These findings were statistically significant on univariate and multivariate analysis. CONCLUSIONS: Following office-based CTR, fewer patients filled opioid prescriptions, and filled prescriptions had lower MME. This likely reflects patient and provider attitudes about pain control and opioid utilization. Further patient- and provider-level investigation may provide additional insights that could aid in efforts to reduce perioperative opioid utilization across surgical settings.

4.
Viruses ; 16(4)2024 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-38675924

RESUMO

In people living with HIV (PLHIV), integrase strand transfer inhibitors (INSTIs) are part of the first-line combination antiretroviral therapy (cART), while non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens are alternatives. Distinct cART regimens may variably influence the risk for non-AIDS comorbidities. We aimed to compare the metabolome and lipidome of INSTI and NNRTI-based regimens. The 2000HIV study includes asymptomatic PLHIV (n = 1646) on long-term cART, separated into a discovery cohort with 730 INSTI and 617 NNRTI users, and a validation cohort encompassing 209 INSTI and 90 NNRTI users. Baseline plasma samples from INSTI and NNRTI users were compared using mass spectrometry-based untargeted metabolomic (n = 500) analysis. Perturbed metabolic pathways were identified using MetaboAnalyst software. Subsequently, nuclear magnetic resonance spectroscopy was used for targeted lipoprotein and lipid (n = 141) analysis. Metabolome homogeneity was observed between the different types of INSTI and NNRTI. In contrast, higher and lower levels of 59 and 45 metabolites, respectively, were found in the INSTI group compared to NNRTI users, of which 77.9% (81/104) had consistent directionality in the validation cohort. Annotated metabolites belonged mainly to 'lipid and lipid-like molecules', 'organic acids and derivatives' and 'organoheterocyclic compounds'. In pathway analysis, perturbed 'vitamin B1 (thiamin) metabolism', 'de novo fatty acid biosynthesis', 'bile acid biosynthesis' and 'pentose phosphate pathway' were detected, among others. Lipoprotein and lipid levels in NNRTIs were heterogeneous and could not be compared as a group. INSTIs compared to individual NNRTI types showed that HDL cholesterol was lower in INSTIs compared to nevirapine but higher in INSTIs compared to doravirine. In addition, LDL size was lower in INSTIs and nevirapine compared to doravirine. NNRTIs show more heterogeneous cardiometabolic effects than INSTIs, which hampers the comparison between these two classes of drugs. Targeted lipoproteomic and lipid NMR spectroscopy showed that INSTI use was associated with a more unfavorable lipid profile compared to nevirapine, which was shifted to a more favorable profile for INSTI when substituting nevirapine for doravirine, with evidently higher fold changes. The cardiovascular disease risk profile seems more favorable in INSTIs compared to NNRTIs in untargeted metabolomic analysis using mass-spectrometry.


Assuntos
Infecções por HIV , Inibidores de Integrase de HIV , Inibidores da Transcriptase Reversa , Humanos , Infecções por HIV/tratamento farmacológico , Inibidores da Transcriptase Reversa/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Inibidores de Integrase de HIV/uso terapêutico , Metaboloma/efeitos dos fármacos , Fármacos Anti-HIV/uso terapêutico , Metabolômica , Estudos de Coortes , Terapia Antirretroviral de Alta Atividade
5.
J Hazard Mater ; 469: 133948, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38493633

RESUMO

Bioaccessibility and relative bioavailability of As, Cd, Pb and Sb was investigated in 30 legacy gold mining wastes (calcine sands, grey battery sands, tailings) from Victorian goldfields (Australia). Pseudo-total As concentration in 29 samples was 1.45-148-fold higher than the residential soil guidance value (100 mg/kg) while Cd and Pb concentrations in calcine sands were up to 2.4-fold and 30.1-fold higher than the corresponding guidance value (Cd: 20 mg/kg and Pb: 300 mg/kg). Five calcine sands exhibited elevated Sb (31.9-5983 mg/kg), although an Australian soil guidance value is currently unavailable. Arsenic bioaccessibility (n = 30) and relative bioavailability (RBA; n = 8) ranged from 6.10-77.6% and 10.3-52.9% respectively. Samples containing > 50% arsenopyrite/scorodite showed low As bioaccessibility (<20.0%) and RBA (<15.0%). Co-contaminant RBA was assessed in 4 calcine sands; Pb RBA ranged from 73.7-119% with high Pb RBA associated with organic and mineral sorbed Pb and, lower Pb RBA observed in samples containing plumbojarosite. In contrast, Cd RBA ranged from 55.0-67.0%, while Sb RBA was < 5%. This study highlights the importance of using multiple lines of evidence during exposure assessment and provides valuable baseline data for co-contaminants associated with legacy gold mining activities.


Assuntos
Arsênio , Poluentes do Solo , Arsênio/análise , Cádmio , Antimônio , Chumbo , Ouro , Areia , Disponibilidade Biológica , Poluentes do Solo/análise , Austrália , Solo , Mineração
6.
J Vitreoretin Dis ; 8(2): 138-143, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38465361

RESUMO

Purpose: To evaluate the risk factors for the development of concurrent or delayed-onset rhegmatogenous retinal detachment (RRD) related to endophthalmitis as well as the anatomic and visual outcomes with subsequent RRD repair. Methods: In this retrospective case study, a 2-tailed t test (continuous) and Fisher exact test were used to determine statistical significance of the observed findings. The relative risk (RR) and 95% CIs were calculated to assess statistical significance. Results: Of the 170 patients included, 22 were found to have a concurrent or subsequent RRD. Initial treatment with pars plana vitrectomy (PPV) (RR, 3.544; 95% CI, 1.650-7.614), aphakia (RR, 4.150; 95% CI, 1.434-12.011), endogenous endophthalmitis (RR, 2.684; 95% CI, 1.065-6.764), and posterior synechiae (RR, 3.026; 95% CI, 1.408-6.505) were statistically significant risk factors for RRD. Anatomically successful repair was achieved in 77.7% of patients. Conclusions: In addition to preexisting risk factors, the initial treatment of endophthalmitis may be a significant risk factor for RRD development, with a higher incidence of subsequent RRD in patients who have PPV as the initial treatment for endophthalmitis.

7.
Chem Sci ; 15(12): 4458-4465, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38516072

RESUMO

The palladium-mediated uncaging reaction of allene substrates remains a promising yet often overlooked strategy in the realm of bioorthogonal chemistry. This method exhibits high kinetic rates, rivaling those of the widely employed allylic and propargylic protecting groups. In this study, we investigate into the mechanistic aspects of the C-O bond-cleavage deallenylation reaction, examining how chloride levels influence the kinetics when triggered by Pd(ii) complexes. Focusing on the deallenylation of 1,2-allenyl protected 4-methylumbelliferone promoted by Allyl2Pd2Cl2, our findings reveal that reaction rates are higher in environments with lower chloride concentrations, mirroring intracellular conditions, compared to elevated chloride concentrations typical of extracellular conditions. Through kinetic and spectroscopic experiments, combined with DFT calculations, we uncover a detailed mechanism that identifies AllylPd(H2O)2 as the predominant active species. These insights provide the basis for the design of π-allylpalladium catalysts suited for selective uncaging within specific cellular environments, potentially enhancing targeted therapeutic applications.

8.
Small ; 20(17): e2307728, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38263806

RESUMO

Herein, the structure of integrated M3D inverters are successfully demonstrated where a chemical vapor deposition (CVD) synthesized monolayer WSe2 p-type nanosheet FET is vertically integrated on top of CVD synthesized monolayer MoS2 n-type film FET arrays (2.5 × 2.5 cm) by semiconductor industry techniques, such as transfer, e-beam evaporation (EBV), and plasma etching processes. A low temperature (below 250 °C) is employed to protect the WSe2 and MoS2 channel materials from thermal decomposition during the whole fabrication process. The MoS2 NMOS and WSe2 PMOS device fabricated show an on/off current ratio exceeding 106 and the integrated M3D inverters indicate an average voltage gain of ≈9 at VDD = 2 V. In addition, the integrated M3D inverter demonstrates an ultra-low power consumption of 0.112 nW at a VDD of 1 V. Statistical analysis of the fabricated inverters devices shows their high reliability, rendering them suitable for large-area applications. The successful demonstration of M3D inverters based on large-scale 2D monolayer TMDs indicate their high potential for advancing the application of 2D TMDs in future integrated circuits.

9.
Environ Sci Pollut Res Int ; 31(6): 9000-9010, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38183546

RESUMO

Many vulture species worldwide are declining at alarming rates due to a variety of anthropogenic causes, including exposure to pollutants and pharmaceuticals through consumption of contaminated carrion. However, little is known about the extent to which vultures are exposed to various contaminants as well as toxicity thresholds for trace elements and heavy metals. Our objective was to quantify levels of trace elements and heavy metals within black vulture (Coragyps atratus) and turkey vulture (Cathartes aura) tissues to determine the extent to which populations in the Southeastern United States are exposed to carrion that contains high levels of contaminants. We collected 34 black vulture liver samples and examined differences in trace element and heavy metal concentrations between sexes and age classes (adult and juvenile). Further, we collected 81 blood and 42 feather samples from additional black and turkey vultures and compared differences between species and age classes. We found similar element concentrations between juvenile and adult black vultures with the exception of Cu, where levels were higher in juveniles compared to adults. However, we did observe substantial differences in element concentrations between species for both blood and feather samples, with black vultures generally having higher concentrations of most elements. Our data revealed higher element levels in both species compared to toxicity thresholds found in other bird of prey species, such as blood and liver toxicity threshold suggestions for Pb poisoning in Falconiformes. Further, while average contaminant levels were generally low, extreme outliers were observed for some elements, including Pb, suggesting some individuals were exposed to high levels of potentially toxic elements. More research is needed to better understand contaminant exposure in black and turkey vultures across a broader geographic region, as well as elucidate toxicity thresholds and non-lethal impacts of contaminant exposure in these species.


Assuntos
Epilepsia , Falconiformes , Metais Pesados , Oligoelementos , Humanos , Animais , Chumbo , Aves , Sudeste dos Estados Unidos
10.
Annu Rev Med ; 75: 391-399, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-37729030

RESUMO

Hospital at Home (HaH) provides hospital-level services in the home to eligible patients who would otherwise require facility-based hospitalization. In the last two decades, studies have shown that HaH can improve patient outcomes and satisfaction and reduce hospital readmissions. Improved technology and greater experience with the model have led to expansion in the scope of patients served and services provided by the model, but dissemination in the United States has been hampered by lack of insurance coverage until recently. HaH is likely at the tipping point for wide adoption in the United States. To realize its full benefits, HaH will need to continue volume expansion to achieve culture change in clinical practice as facilitated by increased insurance coverage, technological advancements, and improved workforce expertise. It is also essential that HaH programs maintain high-quality acute hospital care, ensure that their benefits can be accessed by hard-to-reach rural populations, and continue to advance health equity.


Assuntos
Hospitalização , Readmissão do Paciente , Humanos , Estados Unidos , Hospitais
11.
Environ Pollut ; 341: 122881, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37935301

RESUMO

In this study, smelter contaminated soil was treated with various soil amendments (ferric sulfate [Fe2(SO4)3], triple superphosphate [TSP] and biochar) to determine their efficacy in immobilizing soil lead (Pb) and arsenic (As). In soils incubated with ferric sulfate (0.6M), gastric phase Pb bioaccessibility was reduced from 1939 ± 17 mg kg-1 to 245 ± 4.7 mg kg-1, while intestinal phase bioaccessibility was reduced from 194 ± 25 mg kg-1 to 11.9 ± 3.5 mg kg-1, driven by the formation of plumbojarosite. In TSP treated soils, there were minor reductions in gastric phase Pb bioaccessibility (to 1631 ± 14 mg kg-1) at the highest TSP concentration (6000 mg kg-1) although greater reductions were observed in the intestinal phase, with bioaccessibility reduced to 9.3 ± 2.2 mg kg-1. Speciation analysis showed that this was primarily driven by the formation of chloropyromorphite in the intestinal phase following Pb and phosphate solubilization in the low pH gastric fluid. At the highest concentration (10% w/w), biochar treated soils showed negligible decreases in Pb bioaccessibility in both gastric and intestinal phases. Validation of bioaccessibility outcomes using an in vivo mouse assay led to similar results, with treatment effect ratios (TER) of 0.20 ± 0.01, 0.76 ± 0.11 and 1.03 ± 0.10 for ferric sulfate (0.6M), TSP (6000 mg kg-1) and biochar (10% w/w) treatments. Results of in vitro and in vivo assays showed that only ferric sulfate treatments were able to significantly reduce As bioaccessibility and bioavailability with TER at the highest application of 0.06 ± 0.00 and 0.14 ± 0.04 respectively. This study highlights the potential application of ferric sulfate treatment for the immobilization of Pb and As in co-contaminated soils.


Assuntos
Arsênio , Poluentes do Solo , Animais , Camundongos , Arsênio/análise , Chumbo , Solo , Disponibilidade Biológica , Poluentes do Solo/análise , Resultado do Tratamento
12.
Eco Environ Health ; 2(3): 107-116, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38074988

RESUMO

Alcohol consumption alters gut microflora and damages intestinal tight junction barriers, which may affect arsenic (As) oral bioavailability. In this study, mice were exposed to arsenate in the diet (6 µg/g) over a 3-week period and gavaged daily with Chinese liquor (0.05 or 0.10 mL per mouse per day). Following ingestion, 78.0% and 72.9% of the total As intake was absorbed and excreted via urine when co-exposed with liquor at daily doses of 0.05 or 0.10 mL, significantly greater than when As was supplied alone (44.7%). Alcohol co-exposure significantly altered gut microbiota but did not significantly alter As biotransformation in the intestinal tract or tissue. Significantly lower relative mRNA expression was observed for genes encoding for tight junctions in the ileum of liquor co-exposed mice, contributing to greater As bioavailability attributable to enhanced As absorption via the intestinal paracellular pathway. However, As concentration in the liver, kidney, and intestinal tissue of liquor-treated mice was decreased by 24.4%-42.6%, 27.5%-38.1%, and 28.1%-48.9% compared to control mice. This was likely due to greater renal glomerular filtration rate induced by alcohol, as suggested by significantly lower expression of genes encoding for renal tight junctions. In addition, in mice gavaged daily with 0.05 mL liquor, the serum antidiuretic hormone level was significantly lower than control mice (2.83 ± 0.59 vs. 5.40 ± 1.10 pg/mL), suggesting the diuretic function of alcohol consumption, which may facilitate As elimination via urine. These results highlight that alcohol consumption has a significant impact on the bioavailability and accumulation of As.

13.
Environ Sci Technol ; 57(48): 19463-19472, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37943691

RESUMO

Prebiotics may stimulate beneficial gut microorganisms. However, it remains unclear whether they can lower the oral bioavailability of early life arsenic (As) exposure via regulating gut microbiota and altering As biotransformation along the gastrointestinal (GI) tract. In this study, weanling mice were exposed to arsenate (iAsV) via diet (7.5 µg As g-1) amended with fructooligosaccharides (FOS), galactooligosaccharides (GOS), and inulin individually at 1% and 5% (w/w). Compared to As exposure control mice, As concentrations in mouse blood, liver, and kidneys and As urinary excretion factor (UEF) were reduced by 43.7%-74.1% when treated with 5% GOS. The decrease corresponded to a significant proliferation of Akkermansia and Psychrobacter, reduced percentage of inorganic arsenite (iAsIII) and iAsV by 47.4% and 65.4%, and increased proportion of DMAV in intestinal contents by 101% in the guts of mice treated with 5% GOS compared to the As control group. In contrast, FOS and inulin either at l% or 5% did not reduce As concentration in mouse blood, liver, and kidneys or As UEF. These results suggest that GOS supplementation may be a gut microbiota-regulating approach to lower early life As exposure via stimulating the growth of Akkermansia and Psychrobacter and enhancing As methylation in the GI tract.


Assuntos
Arsênio , Microbioma Gastrointestinal , Camundongos , Animais , Inulina/metabolismo , Prebióticos , Fígado/metabolismo
14.
J Am Heart Assoc ; 12(20): e030606, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37804189

RESUMO

Background Cardiovascular disease is a major cause of morbidity and mortality in people living with HIV, who are at higher risk than the general population. We assessed, in a large cohort of people living with HIV, which cardiovascular, HIV-specific, and lipoproteomic markers were associated with carotid intima-media thickness (cIMT) and carotid plaque presence. We also studied guideline adherence on lipid-lowering medication in individuals with high and very high risk for cardiovascular disease. Methods and Results In 1814 individuals with a median (interquartile range) age of 53 (44-60) years, we found a carotid plaque in 909 (50.1%) and a median (interquartile range) intima-media thickness of 0.66 (0.57-0.76) mm. Ultrasonography was used for the assessment of cIMT and plaque presence. Univariable and multivariable regression models were used for associations with cIMT and presence of plaques. Age, Black race, body mass index, type 2 diabetes, and smoking (pack years) were all positively associated with higher cIMT. Levels of high-density lipoprotein cholesterol, specifically medium and large high-density lipoprotein subclasses, were negatively associated with higher cIMT. Only age and prior myocardial infarction were positively related to the presence of a carotid plaque. Lipid-lowering treatment was prescribed in one-third of people living with HIV, who are at high and very high risk for cardiovascular disease. Conclusions Traditional cardiovascular risk factors were significantly associated with higher cIMT but not with carotid plaques, except for age. HIV-specific factors were not associated with both ultrasound measurements. Future studies are needed to elucidate which factors contribute to plaque formation. Improvement of guideline adherence on prescription of lipid-lowering treatment in high- and very high-risk patients for cardiovascular disease is recommended. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03994835.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Infecções por HIV , Placa Aterosclerótica , Pré-Escolar , Humanos , Pessoa de Meia-Idade , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/complicações , Espessura Intima-Media Carotídea , Diabetes Mellitus Tipo 2/complicações , Fatores de Risco de Doenças Cardíacas , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Lipoproteínas HDL/uso terapêutico , Placa Aterosclerótica/complicações , Fatores de Risco
15.
Proc Natl Acad Sci U S A ; 120(44): e2306177120, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37871210

RESUMO

Lepidopterans affect crop production worldwide. The use of transgenes encoding insecticidal proteins from Bacillus thuringiensis (Bt) in crop plants is a well-established technology that enhances protection against lepidopteran larvae. Concern about widespread field-evolved resistance to Bt proteins has highlighted an urgent need for new insecticidal proteins with different modes or sites of action. We discovered a new family of insecticidal proteins from ferns. The prototype protein from Pteris species (Order Polypodiales) and variants from two other orders of ferns, Schizaeales and Ophioglossales, were effective against important lepidopteran pests of maize and soybean in diet-based assays. Transgenic maize and soybean plants producing these proteins were more resistant to insect damage than controls. We report here the crystal structure of a variant of the prototype protein to 1.98 Å resolution. Remarkably, despite being derived from plants, the structure resembles the 3-domain Cry proteins from Bt but has only two out of three of their characteristic domains, lacking the C-terminal domain which is typically required for their activities. Two of the fern proteins were effective against strains of fall armyworm that were resistant to Bt 3-domain Cry proteins Cry1Fa or Cry2A.127. This therefore represents a novel family of insecticidal proteins that have the potential to provide future tools for pest control.


Assuntos
Bacillus thuringiensis , Gleiquênias , Inseticidas , Traqueófitas , Animais , Inseticidas/metabolismo , Bacillus thuringiensis/genética , Bacillus thuringiensis/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Controle Biológico de Vetores , Endotoxinas/genética , Endotoxinas/metabolismo , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/metabolismo , Traqueófitas/metabolismo , Zea mays/metabolismo
16.
J Phys Chem B ; 127(39): 8456-8467, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37747822

RESUMO

Vibrational sum frequency generation (SFG) spectroscopy has been extensively used for obtaining structural information of molecular functional groups at two-dimensional (2D) interfaces buried in the gas or liquid medium. Although the SFG experiment can be done elegantly, interpreting the measured intensity in terms of molecular orientation with respect to the lab coordinate is quite complicated. One of the main reasons is the difficulty of determining the hyperpolarizability tensors of even simple molecules that govern their SFG responses. The single-bond polarizability derivative model has been proposed to estimate the relative magnitude of SFG-active hyperpolarizability by assuming that the perturbation associated to each vibration is negligible. In this study, density functional theory was used to calculate the polarizability and dipole derivative tensors of the CH3 stretch mode of CH3I, CH3CH2I, CH3OH, and CH3CH2OH. Then, the hyperpolarizability tensors of symmetric and asymmetric vibration modes were calculated considering the Boltzmann distribution of representative conformers, which allowed us to theoretically calculate their SFG intensities at all polarization combinations as a function of the tilt angle of the CH3 group with respect to the surface normal direction. Then, the ratios of the calculated SFG intensities for the CH3 symmetric and asymmetric stretch peaks used in experimental studies for the CH3 tilt angle determination were compared. This comparison clearly showed that the effect of vibrational coupling among neighboring functional groups is significant and cannot be assumed to be negligible. This study presents new parameters that can be used in determining the average tilt angle of the CH3 group at the 2D interface with SFG measurements as well as limitations of the method.

17.
Med Care ; 61(11): 805-812, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37733394

RESUMO

OBJECTIVES: To evaluate the effectiveness and safety of Rehabilitation-at-Home (RaH), which provides high-frequency, multidisciplinary post-acute rehabilitative services in patients' homes. DESIGN: Comparative effectiveness analysis. SETTING AND PARTICIPANTS: Medicare Fee-For-Service patients who received RaH in a Center for Medicare and Medicaid Innovation Center Demonstration during 2016-2017 (N=173) or who received Medicare Skilled Nursing Facility (SNF) care in 2016-2017 within the same geographic service area with similar inclusion and exclusion criteria (N=5535). METHODS: We propensity-matched RaH participants to a cohort of SNF patients using clinical and demographic characteristics with exact match on surgical and non-surgical hospitalizations. Outcomes included hospitalization within 30 days of post-acute admission, death within 30 days of post-acute discharge, length of stay, falls, use of antipsychotic medication, and discharge to community. RESULTS: The majority of RaH participants were older than or equal to 85 years (57.8%) and non-Hispanic white (72.2%) with mean hospital length of stay of 8.1 (SD 7.6) days. In propensity-matched analyses, 10.1% (95% CI: 0.5%, 19.8) and 4.2% (95% CI: 0.1%, 8.5%) fewer RaH participants experienced hospital readmission and death, respectively. RaH participants had, on average, 2.8 fewer days (95% CI 1.4, 4.3) of post-acute care; 11.4% (95% CI: 5.2%, 17.7%) fewer RaH participants experienced fall; and 25.8% (95% CI: 17.8%, 33.9%) more were discharged to the community. Use of antipsychotic medications was no different. CONCLUSIONS AND IMPLICATIONS: RaH is a promising alternative to delivering SNF-level post-acute RaH. The program seems to be safe, readmissions are lower, and transition back to the community is improved.

18.
Environ Sci Technol ; 57(34): 12838-12846, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37587565

RESUMO

As MPs are released into the soil, various equilibrium statuses are expected. MPs could play roles as a "source," a "cleaner," or a "sink" of HOCs. Three types of MPs (LDPE, PLA, and PS) were selected to study their effect on polychlorinated biphenyl (PCBs) relative bioavailability (RBA) measured by a mouse model. As a "source" of HOCs, exposure to MP-sorbed PCBs resulted in their accumulation in adipose tissue with PCB RBA as 101 ± 6.73% for LDPE, 76.2 ± 19.2% for PLA, and 9.22 ± 2.02% for PS. The addition of 10% MPs in PCB-contaminated soil led to a significant (p < 0.05) reduction in PCB RBA (52.2 ± 16.7%, 49.3 ± 4.85%, and 47.1 ± 5.99% for LDPE, PLA, and PS) compared to control (75.0 ± 4.26%), implying MPs acted as "cleaner" by adsorbing PCBs from the digestive system and reducing PCB accumulation. MPs acted as a "sink" for PCBs in contaminated soil after aging, but the sink effect varied among MP types with more pronounced effect for LDPE than PLA and PS. Therefore, the role played by MPs in bioavailability of HOCs closely depended on the MP types as well as the equilibrium status among MPs, soil, and HOCs.


Assuntos
Microplásticos , Bifenilos Policlorados , Animais , Camundongos , Disponibilidade Biológica , Plásticos , Polietileno , Poliésteres
19.
Environ Sci Technol ; 57(35): 12981-12990, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37615500

RESUMO

Few studies have investigated the long-term effect of exposure to arsenic (As), lead (Pb), and cadmium (Cd) via drinking water at the provisional guideline values on gut microflora. In this study, male and female mice were exposed to water As, Pb, or Cd at 10, 10, or 5 µg L-1 for 6 months. At the end of the exposure, the net weight gain of male mice exposed to As and Pb (9.91 ± 1.35 and 11.2 ± 1.50 g) was significantly (p < 0.05) lower compared to unexposed control mice (14.1 ± 3.24 g), while this was not observed for female mice. Relative abundance of Akkermansia, a protective gut bacterium against intestinal inflammation, was reduced from 29.7% to 3.20%, 4.83%, and 17.0% after As, Pb, and Cd exposure in male mice, which likely caused chronic intestinal inflammation, as suggested by 2.81- to 9.60-fold higher mRNA levels of pro-inflammatory factors in ileal enterocytes of male mice. These results indicate that long-term exposure to drinking water As, Pb, and Cd at concentrations equivalent to the China provisional guideline values can cause loss of protective bacteria and lead to chronic intestinal inflammation, thereby affecting body weight gain in male mice.


Assuntos
Arsênio , Água Potável , Microbioma Gastrointestinal , Feminino , Masculino , Animais , Camundongos , Cádmio/toxicidade , Chumbo , Inflamação/induzido quimicamente , Aumento de Peso
20.
Structure ; 31(10): 1166-1173.e6, 2023 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-37572661

RESUMO

Cellulose is an abundant cell wall component of land plants. It is synthesized from UDP-activated glucose molecules by cellulose synthase, a membrane-integrated processive glycosyltransferase. Cellulose synthase couples the elongation of the cellulose polymer with its translocation across the plasma membrane. Here, we present substrate- and product-bound cryogenic electron microscopy structures of the homotrimeric cellulose synthase isoform-8 (CesA8) from hybrid aspen (poplar). UDP-glucose binds to a conserved catalytic pocket adjacent to the entrance to a transmembrane channel. The substrate's glucosyl unit is coordinated by conserved residues of the glycosyltransferase domain and amphipathic interface helices. Site-directed mutagenesis of a conserved gating loop capping the active site reveals its critical function for catalytic activity. Molecular dynamics simulations reveal prolonged interactions of the gating loop with the substrate molecule, particularly across its central conserved region. These transient interactions likely facilitate the proper positioning of the substrate molecule for glycosyl transfer and cellulose translocation.


Assuntos
Celulose , Glucosiltransferases , Celulose/química , Glucosiltransferases/química , Glucose , Difosfato de Uridina
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