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1.
ACS Omega ; 9(17): 19182-19192, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38708195

ABSTRACT

Lightweight biobased insulation polyurethane (BPU) composite foams with high fire-resistance efficiency are interested in building effective energy and low environmental impact today. This study focuses on manufacturing lightweight BPU from liquefied bamboo polyols and biomass resources, including rice husk and wood flour. Then, they are combined with three flame retardant (FR) additives, such as aluminum diethyl phosphinate, aluminum trihydroxide, and diammonium phosphate, to improve their fire resistance performance. The physicochemical properties, microstructure, thermal stability, mechanical properties, and flame-retardant properties of the BPU composites are characterized to optimize their compromise properties. The results showed that composites with optimized FRs achieved UL94 V-0 and those with nonoptimized FRs reached UL94 HB. The limiting oxygen index exhibited that the fire resistance of BPU composites could increase up to 21-37% within FR additives. In addition, the thermal stability of BPU composites was significantly improved in a temperature range of 300-700 °C and the compressive strength of the BPU composites was also enhanced with the presence of FRs. The scanning electron microscopy observation showed an influence of FRs on the morphology and cell size of the BPU composites. The bio-PU-derived samples in this study showed significantly low thermal conductivity values, demonstrating their remarkable thermal insulation effectiveness.

2.
Toxins (Basel) ; 16(5)2024 May 09.
Article in English | MEDLINE | ID: mdl-38787068

ABSTRACT

Botulinum toxin (BoNT) injection can safely be done as an office-based procedure, but can be painful itself, especially when injecting pelvic floor muscles to treat chronic pelvic pain (CPP). Mindfulness interventions may reduce procedure-associated acute anxiety and pain. We applied mindfulness techniques to increase the tolerability of office-based pelvic floor BoNT injections in women with CPP. Women enrolled in a clinical trial of BoNT for endometriosis-associated CPP were offered a brief, guided mindfulness session before and/or after transvaginal injection. Anxiety, pain, and dysphoria were rated on a 0-10 numerical rating scale (NRS) before and after each mindfulness session. Eight women underwent mindfulness sessions. Five participants had a session before and two after the transvaginal injection. One participant had two sessions: one before and one after separate injections. All six women completing a session prior to injection had at least moderate anxiety, which lessened after the mindfulness session (median NRS change: -3.3/10). All three women reporting injection-associated pain experienced less intense pain following the post-injection session (median NRS change: -3/10). Three women experiencing dysphoria improved after the session (median NRS change: -3/10). A brief, guided mindfulness session may lessen acute pain, anxiety, and dysphoria associated with office-based transvaginal BoNT injection.


Subject(s)
Chronic Pain , Mindfulness , Pelvic Floor , Pelvic Pain , Humans , Female , Pelvic Pain/drug therapy , Pelvic Pain/therapy , Adult , Chronic Pain/drug therapy , Chronic Pain/therapy , Pelvic Floor/physiopathology , Anxiety/therapy , Anxiety/drug therapy , Middle Aged , Botulinum Toxins/administration & dosage , Endometriosis/drug therapy , Endometriosis/psychology , Endometriosis/complications
3.
Nat Hum Behav ; 8(5): 797, 2024 May.
Article in English | MEDLINE | ID: mdl-38724649
4.
J Pers ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38757772

ABSTRACT

OBJECTIVE: This research explored arousal levels as a motivating factor for solitude-seeking. We hypothesized that solitude becomes more desirable when high-arousal emotions were heightened and individual differences in extraversion and neuroticism would moderate this pattern. METHOD: We tracked individuals' hourly experiences throughout a day. We assessed their high-arousal positive (e.g., excitement) and negative emotions (e.g., tension), whether they were alone or with others, and their preferred situation at the time of the signal. We gathered 4338 surveys from 362 participants, with 103 participants completing all hourly surveys. RESULTS: Preference for and incidence of solitude changed throughout the day. Contrary to our hypotheses, lagged analyses did not indicate high-arousal emotions predicting reports of being alone an hour later. However, individuals were more likely to express a preference for solitude while experiencing high-arousal negative emotions, and less so while experiencing positive emotions. Younger individuals display stronger preference for solitude during experiences of high-arousal negative emotions. Extraversion and neuroticism did not moderate these patterns. CONCLUSIONS: The results highlight the distinctive appeal of solitude as a space for young adults to deal with negative emotions. We discussed how these findings are connected to existing literature and implications for future research.

5.
Plant Cell Physiol ; 65(6): 986-998, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38590126

ABSTRACT

Isotope labeling coupled with mass spectrometry imaging (MSI) presents a potent strategy for elucidating the dynamics of metabolism at cellular resolution, yet its application to plant systems is scarce. It has the potential to reveal the spatio-temporal dynamics of lipid biosynthesis during plant development. In this study, we explore its application to galactolipid biosynthesis of an aquatic plant, Lemna minor, with D2O labeling. Specifically, matrix-assisted laser desorption/ionization-MSI data of two major galactolipids in L. minor, monogalactosyldiacylglycerol and digalactosyldiacylglycerol, were studied after growing in 50% D2O media over a 15-day time period. When they were partially labeled after 5 d, three distinct binomial isotopologue distributions were observed corresponding to the labeling of partial structural moieties: galactose only, galactose and a fatty acyl chain and the entire molecule. The temporal change in the relative abundance of these distributions follows the expected linear pathway of galactolipid biosynthesis. Notably, their mass spectrometry images revealed the localization of each isotopologue group to the old parent frond, the intermediate tissues and the newly grown daughter fronds. Besides, two additional labeling experiments, (i) 13CO2 labeling and (ii) backward labeling of completely 50% D2O-labeled L. minor in H2O media, confirm the observations in forward labeling. Furthermore, these experiments unveiled hidden isotopologue distributions indicative of membrane lipid restructuring. This study suggests the potential of isotope labeling using MSI to provide spatio-temporal details in lipid biosynthesis in plant development.


Subject(s)
Araceae , Galactolipids , Isotope Labeling , Galactolipids/metabolism , Galactolipids/biosynthesis , Isotope Labeling/methods , Araceae/metabolism , Araceae/growth & development , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Deuterium Oxide/metabolism
6.
Adv Pharmacol ; 99: 83-124, 2024.
Article in English | MEDLINE | ID: mdl-38467490

ABSTRACT

Synthetic cathinone derivatives comprise a family of psychoactive compounds structurally related to amphetamine. Over the last decade, clandestine chemists have synthesized a consistent stream of innovative cathinone derivatives to outpace governmental regulatory restrictions. Many of these unregulated substances are produced and distributed as designer drugs. Two of the principal chemical scaffolds exploited to expand the synthetic cathinone family are methcathinone and α-pyrrolidinopentiophenone (or α-pyrrolidinovalerophenone, α-PVP). These compounds' main physiological targets are monoamine transporters, where they promote addiction by potentiating dopaminergic neurotransmission. This chapter describes techniques used to study the pharmacodynamic properties of cathinones at monoamine transporters in vitro. Biochemical techniques described include uptake inhibition and release assays in rat brain synaptosomes and in mammalian expression systems. Electrophysiological techniques include current measurements using the voltage clamp technique. We describe a Ca2+ mobilization assay wherein voltage-gated Ca2+ channels function as reporters to study the action of synthetic cathinones at monoamine transporters. We discuss results from systematic structure-activity relationship studies on simple and complex cathinones at monoamine transporters with an emphasis on identifying structural moieties that modulate potency and selectivity at these transporters. Moreover, different profiles of selectivity at monoamine transporters directly predict compounds associated with behavioral and subjective effects within animals and humans. In conclusion, clarification of the structural aspects of compounds which modulate potency and selectivity at monoamine transporters is critical to identify and predict potential addictive drugs. This knowledge may allow prompt allocation of resources toward drugs that represent the greatest threats after drugs are identified by forensic laboratories.


Subject(s)
Central Nervous System Stimulants , Synthetic Cathinone , Rats , Animals , Humans , Amphetamines , Central Nervous System Stimulants/chemistry , Central Nervous System Stimulants/pharmacology , Pyrrolidines/chemistry , Pyrrolidines/metabolism , Pyrrolidines/pharmacology , Mammals/metabolism
7.
J Am Chem Soc ; 146(12): 8618-8629, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38471106

ABSTRACT

Atomically dispersed first-row transition metals embedded in nitrogen-doped carbon materials (M-N-C) show promising performance in catalytic hydrogenation but are less well-studied for reactions with more complex mechanisms, such as hydrogenolysis. Their ability to catalyze selective C-O bond cleavage of oxygenated hydrocarbons such as aryl alcohols and ethers is enhanced with the participation of ligands directly bound to the metal ion as well as longer-range contributions from the support. In this article, we describe how Fe-N-C catalysts with well-defined local structures for the Fe sites catalyze C-O bond hydrogenolysis. The reaction is facilitated by the N-C support. According to spectroscopic analyses, the as-synthesized catalysts contain mostly pentacoordinated FeIII sites, with four in-plane nitrogen donor ligands and one axial hydroxyl ligand. In the presence of 20 bar of H2 at 170-230 °C, the hydroxyl ligand is lost when N4FeIIIOH is reduced to N4FeII, assisted by the H2 chemisorbed on the support. When an alcohol binds to the tetracoordinated FeII sites, homolytic cleavage of the O-H bond is accompanied by reoxidation to FeIII and H atom transfer to the support. The role of the N-C support in catalytic hydrogenolysis is analogous to the behavior of chemically and redox-non-innocent ligands in molecular catalysts based on first-row transition metal ions and enhances the ability of M-N-Cs to achieve the types of multistep activations of strong bonds needed to upgrade renewable and recycled feedstocks.

8.
J Hand Ther ; 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38320939

ABSTRACT

BACKGROUND: Upper extremity musculoskeletal injuries are common with active-duty Army Soldiers and result in increased limited duty days. Patient satisfaction and surgery rates improve with direct access to occupational therapy in the civilian community. PURPOSE: Examine the amount of time from initial evaluation following an upper extremity musculoskeletal injury (MSKI) to return to full duty plus occupational therapy (OT) utilization in Army Soldiers. STUDY DESIGN: Retrospective observational. METHODS: Electronic health records and profiles from 18,206 US active-duty Army soldiers with MSKI and OT evaluation between 2017-2018 were examined. Repeated measures generalized estimating equations provided the rate ratios (RRs) for OT healthcare utilization (total number of OT evaluations and treatment visits) by days to first OT evaluation and limited duty profile (total days on profile). RESULTS: Soldiers were on average 32.0 (SD = 8.9) y/o, predominantly senior enlisted (45.7%), white (58.0%), male (81.4%), 10.0 (SD = 8.4) years of service, and high school or less educated (51.3%). There were 22,617 UE MSKIs with an OT evaluation and 4936 UE MSKIs with profiles. Compared with UE MSKIs with an OT evaluation on the same day, there was a significant increase in rates of OT utilization for 1-7 days (RR: 1.4, 95% CI: 1.3, 1.5), 8-14 days (RR: 1.3, 95% CI: 1.2, 1.4), 15-30 days (RR: 1.4, 95% CI: 1.3, 1.5), 31-60 days (RR: 1.5, 95% CI: 1.4, 1.6), and +60 days later (RR: 1.6, 95% CI: 1.5, 1.7). Similar differences in rates for limited duty profiles were found. CONCLUSION: A greater number of days between diagnosis of UE MSKI and OT evaluation results in greater rates of OT utilization and longer temporary profile. Results suggest that earlier intervention by OT may decrease recovery and healthcare utilization of soldiers.

9.
J Vasc Surg ; 79(2): 366-381.e1, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37952783

ABSTRACT

OBJECTIVE: In the United States, an estimated $2.8 billion annually is spent on vascular access and its complications. Endovascular arteriovenous fistula (endoAVF) creation is a novel, minimally invasive alternative to traditional surgical AV fistula (sAVF) creation in ≤60% of patients. Although cost effective in single-payer systems, the clinical and financial impact of endoAVF in the United States remains uncertain. METHODS: We constructed a decision tree followed by a probabilistic cohort state-transition model to study the cost effectiveness of endoAVF vs sAVF creation. We conducted a systematic review to obtain input parameters including technical success, maturation, patency, and utility values. We derived costs from the Medicare 2022 fee schedule and from the literature. We used a 5-year time horizon, an annual discount rate of 3% for costs and utilities (measured in quality-adjusted life-years [QALYs]), and the common willingness-to-pay threshold of $50,000. One-way and Monte Carlo probabilistic sensitivity analyses were performed varying technical success, patency, reintervention, cost, and utility parameters. RESULTS: In the base-case scenario, endoAVF ($30,129 average per-person costs, 2.19 QALYs gained, 65% patent at 5 years) was not cost effective compared with sAVF ($12.987 average per-person costs, 2.11 QALYs gained, 66% patent at 5 years), generating an incremental cost-effectiveness ratio of $227,504 per QALY gained. In one-way sensitivity analyses, endoAVF becomes cost effective when the initial cost of sAVF creation exceeds endoAVF by ≥$600 (eg, if endoAVF creation costs ≤$3000 relative to the base-case sAVF cost of $3600), the additional QALYs gained from endoAVF exceeds 0.12 QALYs/year (eg, 0.81 QALYs gained/year from endoAVF compared with base-case sAVF 0.69 QALYs/year), the endoAVF maturation rate is >90% (base case 78%), or the sAVF maturation rate is <65% (base case 78%). Probabilistic sensitivity analysis demonstrated that sAVF remained the optimal strategy in 71% of iterations. CONCLUSIONS: EndoAVF is not cost effective compared with sAVF when modeling 5-year outcomes. The main driver of sAVF remaining cost effective is the four times higher up-front cost for endoAVF creation, as well as a relatively low additional increase in quality of life for endoAVF. It will be important to establish how the endoAVF learning curve contributes to upfront costs and, given the annual cost attributed to vascular access nationally, a randomized controlled trial is warranted.


Subject(s)
Arteriovenous Fistula , Cost-Effectiveness Analysis , Aged , Humans , United States , Quality of Life , Cost-Benefit Analysis , Medicare , Quality-Adjusted Life Years
10.
Semin Vasc Surg ; 36(3): 401-412, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37863612

ABSTRACT

In the past decade, artificial intelligence (AI)-based applications have exploded in health care. In cardiovascular disease, and vascular surgery specifically, AI tools such as machine learning, natural language processing, and deep neural networks have been applied to automatically detect underdiagnosed diseases, such as peripheral artery disease, abdominal aortic aneurysms, and atherosclerotic cardiovascular disease. In addition to disease detection and risk stratification, AI has been used to identify guideline-concordant statin therapy use and reasons for nonuse, which has important implications for population-based cardiovascular disease health. Although many studies highlight the potential applications of AI, few address true clinical workflow implementation of available AI-based tools. Specific examples, such as determination of optimal statin treatment based on individual patient risk factors and enhancement of intraoperative fluoroscopy and ultrasound imaging, demonstrate the potential promise of AI integration into clinical workflow. Many challenges to AI implementation in health care remain, including data interoperability, model bias and generalizability, prospective evaluation, privacy and security, and regulation. Multidisciplinary and multi-institutional collaboration, as well as adopting a framework for integration, will be critical for the successful implementation of AI tools into clinical practice.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , Peripheral Arterial Disease , Humans , Artificial Intelligence , Workflow , Neural Networks, Computer , Peripheral Arterial Disease/diagnostic imaging , Peripheral Arterial Disease/surgery
11.
Ann Vasc Surg ; 97: 163-173, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37586562

ABSTRACT

BACKGROUND: Fenestrated endovascular aneurysm repair (FEVAR) is a well-established treatment approach for juxtarenal and short-neck infrarenal aortic aneurysms. Recommendations and clinical outcomes are lacking for offering FEVAR in patients with chronic kidney disease (CKD). We aimed to compare short- and long-term outcomes for patients with none-to-mild versus moderate-to-severe CKD undergoing FEVAR. METHODS: We retrospectively reviewed consecutive patients undergoing standard FEVAR with Cook devices at a single institution. The cohort was stratified by preoperative CKD stage none-to-mild or moderate-to-severe (CKD 1-2 and CKD 3-5, respectively). The primary outcome was postoperative acute kidney injury (AKI). Secondary outcomes included 30-day perioperative complications, 1- and 5-year rates of overall survival, dialysis, renal target artery patency, endoleak, and reintervention assessed by the Kaplan-Meier method. Aneurysm sac regression, number of surveillance computed tomography (CT) scans, and CKD stage progression were assessed at latest follow-up. Multivariate Cox proportional hazards modeling was used to evaluate the association of CKD stage 3 and stage 4-5 with all-cause mortality, controlling for differences in baseline characteristics. RESULTS: From 2012- to 2022, 184 patients (of which 82% were male) underwent FEVAR with the Cook ZFEN device (mean follow-up 34.3 months). Group CKD 3-5 comprised 77 patients (42%), was older (75.2 vs. 73.0 years, P = 0.04), had increased preoperative creatinine (1.6 vs. 0.9 mg/dL, P < 0.01), and demonstrated increased renal artery ostial calcification (37.7% vs. 21.5%, P = 0.02) compared with Group CKD 1-2. Perioperatively, CKD 3-5 sustained higher estimated blood loss (342 vs. 228 ml, P = 0.01), longer operative times (186 vs. 162 min, P = 0.04), and longer length of stay (3 vs. 2 days, P < 0.01). Kaplan-Meier 1- and 5-year survival estimates were lower for CKD 3-5 (82.3% vs. 95.1%, P < 0.01 and 55.4% vs. 70.8%, P = 0.02). Fewer CKD 3-5 patients remained free from chronic dialysis at 1 year (94.4% vs. 100%, P = 0.015) and 5 years (84.7% vs. 100%, P < 0.01). There were no significant differences in postoperative AKI rate (CKD 1-2 6.5% vs. CKD 3-5 14.3%, P = 0.13), long-term renal artery patency, reinterventions, type I or III endoleak, mean sac regression, or total follow-up CT scans between groups. CKD stage progression occurred in 47 patients (31%) at latest follow-up but did not differ between stratified groups (P = 0.17). On multivariable modeling, age (hazard ratio 1.05, 95% confidence interval 1.01-1.09, P = 0.02) and CKD stage 4-5 (hazard ratio 6.39, 95% confidence interval 2.26-18.05, P < 0.01) were independently associated with mortality. CONCLUSIONS: Preoperative CKD status did not negatively impact the durability or technical success related to aneurysm outcomes after FEVAR. Worsening CKD stage was associated with lower 1- and 5-year overall survival and freedom from dialysis after FEVAR with no statistically significant differences in 30-day or long-term technical aneurysm outcomes.


Subject(s)
Acute Kidney Injury , Aortic Aneurysm, Abdominal , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Renal Insufficiency, Chronic , Humans , Male , Female , Blood Vessel Prosthesis/adverse effects , Aortic Aneurysm, Abdominal/complications , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/surgery , Endovascular Aneurysm Repair , Stents/adverse effects , Endoleak/surgery , Retrospective Studies , Treatment Outcome , Risk Factors , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/diagnosis , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Prosthesis Design
12.
Front Psychiatry ; 14: 1173441, 2023.
Article in English | MEDLINE | ID: mdl-37484662

ABSTRACT

Objectives: From the perspective of person-centered research, the present study aimed to identify the potential profiles of solitude among late adolescents based on their solitary behavior, motivation, attitude, and time alone. In addition, to echo the paradox of solitude, we further explored the links between solitude profiles and adjustment outcomes. Methods: The participants of the study were 355 late adolescents (56.34% female, M age = 19.71 years old) at three universities in Shanghai, China. Measures of solitary behavior, autonomous motivation for solitude, attitude toward being alone, and time spent alone were collected using adolescents' self-report assessments. The UCLA Loneliness Scale, the Beck Depression Inventory, and the Basic Psychological Needs Scales were measured as indices of adjustment. Results: Latent profile analysis revealed four distinct groups: absence of the aloneness group (21.13%), the positive motivational solitude group (29.01%), the negative motivational solitude group (38.03%), and the activity-oriented solitude group (11.83%). Differences emerged among these four groups in terms of loneliness, depressive symptoms, and basic needs satisfaction, with adolescents in the negative motivational solitude group facing the most risk of psychological maladjustment. Conclusion: Findings revealed the possible heterogeneous nature of solitude among Chinese late adolescents and provided a theoretical basis for further understanding of adolescents' solitary state.

13.
ACS Chem Neurosci ; 14(14): 2527-2536, 2023 07 19.
Article in English | MEDLINE | ID: mdl-37406364

ABSTRACT

α-Pyrrolidinohexiophenone (α-PHP) is the one-carbon unit α-extended homolog of the better-known and widely abused synthetic cathinone central stimulant α-PVP ("flakka"); both are now U.S. Schedule I controlled substances. Structurally, α-PVP and α-PHP possess a common terminal N-pyrrolidine moiety and differ only with respect to the length of their α-alkyl chain. Using a synaptosomal assay, we previously reported that α-PHP is at least as potent as α-PVP as a dopamine transporter (DAT) reuptake inhibitor. A systematic structure-activity study of synthetic cathinones (e.g., α-PHP) as DAT reuptake inhibitors (i.e., transport blockers), a mechanism thought responsible for their abuse liability, has yet to be conducted. Here, we examined a series of 4-substituted α-PHP analogues and found that, with one exception, all behaved as relatively (28- to >300-fold) selective DAT versus serotonin transporter (SERT) reuptake inhibitors with DAT inhibition potencies of most falling within a very narrow (i.e., <3-fold) range. The 4-CF3 analogue of α-PHP was a confirmed "outlier" in that it was at least 80-fold less potent than the other analogues and displayed reduced (i.e., no) DAT vs SERT selectivity. Consideration of various physicochemical properties of the CF3 group, relative to that of the other substituents involved here, provided relatively little insight. Unlike with DAT-releasing agents, as previously reported by us, a QSAR study was precluded because of the limited range of empirical results (with the exception of the 4-CF3 analogue) for DAT reuptake inhibition.


Subject(s)
Dopamine Plasma Membrane Transport Proteins , Synthetic Cathinone , Dopamine Plasma Membrane Transport Proteins/metabolism , Pyrrolidines/pharmacology , Pyrrolidines/chemistry , Dopamine Uptake Inhibitors/pharmacology , Dopamine Uptake Inhibitors/chemistry , Structure-Activity Relationship , Serotonin Plasma Membrane Transport Proteins , Selective Serotonin Reuptake Inhibitors
14.
Spine (Phila Pa 1976) ; 48(16): 1117-1126, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37249397

ABSTRACT

STUDY DESIGN: Cohort study. OBJECTIVE: We aimed to evaluate the associations of genetic and nongenetic factors with degenerative cervical myelopathy (DCM). SUMMARY OF BACKGROUND DATA: There is mounting evidence for an inherited predisposition for DCM, but uncertainty remains regarding specific genetic markers involved. Similarly, nongenetic factors are thought to play a role. MATERIALS AND METHODS: Using diagnosis codes from hospital records linked to the UK Biobank cohort, patients with cervical spondylosis were identified followed by the identification of a subset with DCM. Nongenetic variables evaluated included age, sex, race, Townsend deprivation index, body mass index, occupational demands, osteoporosis, and smoking. Genome-wide association analyses were conducted using logistic regression adjusted for age, sex, population principal components, and follow-up. RESULTS: A total of 851 DCM cases out of 2787 cervical spondylosis patients were identified. Several nongenetic factors were independently associated with DCM including age [odds ratio (OR)=1.11, 95% CI=1.01-1.21, P =0.024], male sex (OR=1.63, 95% CI=1.37-1.93, P <0.001), and relative socioeconomic deprivation (OR=1.03, 95% CI=1.00-1.06, P =0.030). Asian race was associated with lower DCM risk (OR=0.44, 95% CI=0.22-0.85, P =0.014). We did not identify genome-wide significant (≤5×10 -8 ) single-nucleotide polymorphisms (SNPs) associated with DCM. The strongest genome-wide signals were at SNP rs67256809 in the intergenic region of the genes LINC02582 and FBXO15 on chromosome 18 ( P =1.12×10 -7 ) and rs577081672 in the GTPBP1 gene on chromosome 22 ( P =2.9×10 -7 ). No SNPs reported in prior DCM studies were significant after adjusting for replication attempts. CONCLUSIONS: Increasing age, male sex, and relative socioeconomic deprivation were identified as independent risk factors for DCM, whereas Asian race was inversely associated. SNPs of potential interest were identified in GTPBP1 and an intergenic region on chromosome 18, but these associations did not reach genome-wide significance. Identification of genetic and nongenetic DCM susceptibility markers may guide understanding of DCM disease processes, inform risk, guide prevention and potentially inform surgical outcomes. LEVEL OF EVIDENCE: Prognostic level III.


Subject(s)
Spinal Cord Diseases , Spondylosis , Humans , Male , Cohort Studies , Genome-Wide Association Study , Spinal Cord Diseases/surgery , Risk Factors , Spondylosis/epidemiology , Spondylosis/genetics , Spondylosis/surgery
15.
JBMR Plus ; 7(4): e10719, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37065629

ABSTRACT

Basic combat training (BCT) is a physically rigorous period at the beginning of a soldier's career that induces bone formation in the tibia. Race and sex are determinants of bone properties in young adults but their influences on changes in bone microarchitecture during BCT are unknown. The purpose of this work was to determine the influence of sex and race on changes in bone microarchitecture during BCT. Bone microarchitecture was assessed at the distal tibia via high-resolution peripheral quantitative computed tomography at the beginning and end of 8 weeks of BCT in a multiracial cohort of trainees (552 female, 1053 male; mean ± standard deviation [SD] age = 20.7 ± 3.7 years) of which 25.4% self-identified as black, 19.5% as race other than black or white (other races combined), and 55.1% as white. We used linear regression models to determine whether changes in bone microarchitecture due to BCT differed by race or sex, after adjusting for age, height, weight, physical activity, and tobacco use. We found that trabecular bone density (Tb.BMD), thickness (Tb.Th), and volume (Tb.BV/TV), as well as cortical BMD (Ct.BMD) and thickness (Ct.Th) increased following BCT in both sexes and across racial groups (+0.32% to +1.87%, all p < 0.01). Compared to males, females had greater increases in Tb.BMD (+1.87% versus +1.40%; p = 0.01) and Tb.Th (+0.87% versus +0.58%; p = 0.02), but smaller increases in Ct.BMD (+0.35% versus +0.61%; p < 0.01). Compared to black trainees, white trainees had greater increases in Tb.Th (+0.82% versus +0.61%; p = 0.03). Other races combined and white trainees had greater increases in Ct.BMD than black trainees (+0.56% and + 0.55% versus +0.32%; both p ≤ 0.01). Changes in distal tibial microarchitecture, consistent with adaptive bone formation, occur in trainees of all races and sexes, with modest differences by sex and race. Published 2023. This article is a U.S. Government work and is in the public domain in the USA. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

16.
Med Sci Sports Exerc ; 55(9): 1533-1539, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37057721

ABSTRACT

PURPOSE: To determine whether changes in menstruation develop in female trainees during BCT and whether changes in body mass, body composition and/or physical activity are associated with menstrual interruption during BCT. METHODS: Female trainees grouped according to self-reported menstrual status in the 12 months before BCT as having regular cycles (RC; n = 352) or MD ( n = 97) completed height, body mass, and body composition assessments and questionnaires before and after BCT. Fisher's exact test and Mann-Whitney U test were used to compare between-group differences in categorical and continuous variables, respectively. Among RC trainees, odds ratios were calculated to examine the influence of changes in body mass, lean mass, and fat mass on a trainee's likelihood to miss a period during BCT. RESULTS: There were no differences in race, height, body mass, body mass index, or physical activity history at pre-BCT between RC and MD ( P > 0.05). Overall, 86% of trainees experienced changes to menstruation during BCT. RC were more likely than MD to have at least one period during BCT (81% vs 69%, respectively, P = 0.01). Among RC, gaining more body mass and lean mass and losing less fat mass were associated with increased odds of missing a period during BCT. CONCLUSIONS: These findings demonstrate that most female trainees experience menstrual changes during BCT. Menstrual cycle interruptions do not appear to align with loss of body or fat mass.


Subject(s)
Menstruation , Military Personnel , Humans , Female , Body Mass Index , Exercise , Body Composition , Menstrual Cycle
17.
N Engl J Med ; 388(12): 1067-1079, 2023 Mar 23.
Article in English | MEDLINE | ID: mdl-36867173

ABSTRACT

BACKGROUND: The benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression have not been extensively studied. METHODS: We conducted a two-step, open-label trial involving adults 60 years of age or older with treatment-resistant depression. In step 1, patients were randomly assigned in a 1:1:1 ratio to augmentation of existing antidepressant medication with aripiprazole, augmentation with bupropion, or a switch from existing antidepressant medication to bupropion. Patients who did not benefit from or were ineligible for step 1 were randomly assigned in step 2 in a 1:1 ratio to augmentation with lithium or a switch to nortriptyline. Each step lasted approximately 10 weeks. The primary outcome was the change from baseline in psychological well-being, assessed with the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales (population mean, 50; higher scores indicate greater well-being). A secondary outcome was remission of depression. RESULTS: In step 1, a total of 619 patients were enrolled; 211 were assigned to aripiprazole augmentation, 206 to bupropion augmentation, and 202 to a switch to bupropion. Well-being scores improved by 4.83 points, 4.33 points, and 2.04 points, respectively. The difference between the aripiprazole-augmentation group and the switch-to-bupropion group was 2.79 points (95% CI, 0.56 to 5.02; P = 0.014, with a prespecified threshold P value of 0.017); the between-group differences were not significant for aripiprazole augmentation versus bupropion augmentation or for bupropion augmentation versus a switch to bupropion. Remission occurred in 28.9% of patients in the aripiprazole-augmentation group, 28.2% in the bupropion-augmentation group, and 19.3% in the switch-to-bupropion group. The rate of falls was highest with bupropion augmentation. In step 2, a total of 248 patients were enrolled; 127 were assigned to lithium augmentation and 121 to a switch to nortriptyline. Well-being scores improved by 3.17 points and 2.18 points, respectively (difference, 0.99; 95% CI, -1.92 to 3.91). Remission occurred in 18.9% of patients in the lithium-augmentation group and 21.5% in the switch-to-nortriptyline group; rates of falling were similar in the two groups. CONCLUSIONS: In older adults with treatment-resistant depression, augmentation of existing antidepressants with aripiprazole improved well-being significantly more over 10 weeks than a switch to bupropion and was associated with a numerically higher incidence of remission. Among patients in whom augmentation or a switch to bupropion failed, changes in well-being and the occurrence of remission with lithium augmentation or a switch to nortriptyline were similar. (Funded by the Patient-Centered Outcomes Research Institute; OPTIMUM ClinicalTrials.gov number, NCT02960763.).


Subject(s)
Antidepressive Agents , Aripiprazole , Bupropion , Lithium Compounds , Nortriptyline , Treatment Switching , Aged , Humans , Antidepressive Agents/adverse effects , Antidepressive Agents/therapeutic use , Aripiprazole/adverse effects , Aripiprazole/therapeutic use , Bupropion/adverse effects , Bupropion/therapeutic use , Depression , Drug Therapy, Combination , Nortriptyline/adverse effects , Nortriptyline/therapeutic use , Lithium Compounds/adverse effects , Lithium Compounds/therapeutic use
18.
Angew Chem Int Ed Engl ; 62(15): e202218770, 2023 Apr 03.
Article in English | MEDLINE | ID: mdl-36789791

ABSTRACT

Possible routes for intra-cluster bond formation (ICBF) in protonated serine dimers have been studied. We found no evidence of ICBF following low energy collision-induced dissociation (in correspondence with previous works), however, we do observe clear evidence for ICBF following photon absorption in the 4.6-14 eV range. Moreover, the comparison of photon-induced dissociation measurements of the protonated serine dimer to those of a protonated serine dipeptide provides evidence that ICBF, in this case, involves peptide bond formation (PBF). The experimental results are supported by ab initio molecular dynamics and exploration of several excited state potential energy surfaces, unraveling a pathway for PBF following photon absorption. The combination of experiments and theory provides insight into the PBF mechanisms in clusters of amino acids, and reveals the importance of electronic excited states reached upon UV/VUV light excitation.

19.
J Vasc Surg ; 77(6): 1669-1673.e1, 2023 06.
Article in English | MEDLINE | ID: mdl-36781115

ABSTRACT

OBJECTIVE: Since 2005, the United States Preventative Services Task Force has recommended abdominal aortic aneurysm (AAA) ultrasound screening for 65- to 75-year-old male ever-smokers. Integrated health systems such as Kaiser Permanente and the Veterans Affairs (VA) health care system report 74% to 79% adherence, but compliance rates in the private sector are unknown. METHODS: The IBM Marketscan Commercial and Medicare Supplemental databases (2006-2017) were queried for male ever-smokers continuously enrolled from age 65 to 75 years. Exclusion criteria were previous history of AAA, connective tissue disorder, and aortic surgery. Patients with abdominal computed tomographic or magnetic resonance imaging from ages 65 to 75 years were also excluded. Screening was defined as a complete abdominal, retroperitoneal, or aortic ultrasound. A logistic mixed-effects model utilizing state as a random intercept was used to identify patient characteristics associated with screening. RESULTS: Of 35,154 eligible patients, 13,612 (38.7%) underwent screening. Compliance varied by state, ranging from 24.4% in Minnesota to 51.6% in Montana (P < .05). Screening activity increased yearly, with 0.7% of screening activity occurring in 2008 vs 22.2% in 2016 (P <.05). In a logistic mixed-effects model adjusting for state as a random intercept, history of hypertension (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.03-1.13), coronary artery disease (OR, 1.17; 95% CI, 1.10-1.22), congestive heart failure (OR, 1.14; 95% CI, 1.01-1.22), diabetes (OR, 1.1; 95% CI, 1.06-1.16), and chronic kidney disease (OR, 1.4; 95% CI, 1.24-1.53) were associated with screening. Living outside of a census-designated metropolitan area was negatively associated with screening (OR, 0.92; 95% CI, 0.87-0.97). CONCLUSIONS: In a private claims database representing 250 million claimants, 38.7% of eligible patients received United States Preventative Services Task Force-recommended AAA screening. Compliance was nearly one-half that of integrated health systems and was significantly lower for patients living outside of metropolitan areas. Efforts to improve early detection of AAA should include targeting non-metropolitan areas and modifying Medicare reimbursement and incentivization strategies to improve guideline adherence.


Subject(s)
Aortic Aneurysm, Abdominal , Coronary Artery Disease , Humans , Male , United States , Aged , Medicare , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/surgery , United States Department of Veterans Affairs , Mass Screening/methods
20.
J Vasc Surg ; 77(6): 1797-1802, 2023 06.
Article in English | MEDLINE | ID: mdl-36758909

ABSTRACT

OBJECTIVE: Survey data suggests that surgical residents spend 20% to 30% of training time using the electronic medical record (EMR), raising concerns about burnout and insufficient operative experience. We characterize trainee EMR activity in the vascular surgery service of a quaternary care center to identify modifiable factors associated with high EMR use. METHODS: Resident activity while on the vascular surgery service was queried from the EMR. Weekends and holidays were excluded to focus on typical staffing periods. Variables including daily time spent, post-graduate year (PGY), remote access via mobile device or personal laptop, and patient census including operative caseload were extracted. Univariate analysis was performed with t tests and χ2 tests where appropriate. We then fit a linear mixed-effects model with normalized daily EMR time as the outcome variable, random slopes for resident and patient census, and fixed effects of PGY level, academic year, and fractional time spent using remote access. RESULTS: EMR activity for 53 residents from July 2015 to June 2019 was included. The mean daily EMR usage was 1.6 hours, ranging from 3.6 hours per day in PGY1 residents to 1.1 hours in PGY4 to 5 residents. Across all PGYs, the most time-consuming EMR activities were chart review (43.0%-46.6%) and notes review (22.4%-27.0%). In the linear mixed-effects model, increased patient census was associated with increased daily EMR usage (Coefficient = 0.61, P-value < .001). Resident seniority (Coefficient = -1.2, P-value < .001) and increased remote access (Coefficient = -0.44, P-value < .001) were associated with reduced daily EMR usage. Over the study period, total EMR usage decreased significantly from the 2015/2016 academic year to the 2018/2019 academic year (mean difference, 2.4 hours vs 1.78; P-value < .001). CONCLUSIONS: In an audit of EMR activity logs on a vascular surgery service, mean EMR time was 1.6 hours a day, which is lower than survey estimates. Resident seniority and remote access utilization were associated with reduced time spent on the EMR, independent of patient census. Although increasing EMR accessibility via mobile devices and personal computers have been hypothesized to contribute to poor work-life balance, our study suggests a possible time-saving effect by enabling expedient access for data review, which constitutes the majority of resident EMR activity. Further research in other institutions and specialties is needed for external validation and exploring implications for resident wellness initiatives.


Subject(s)
Internship and Residency , Workload , Humans , Electronic Health Records , Vascular Surgical Procedures
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