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1.
Psychiatry Res ; 339: 116101, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39068897

RESUMO

Longitudinal research examining children's mental health (MH) over the course of the COVID-19 pandemic is scarce. We examined trajectories of depression and anxiety over two pandemic years among children with and without MH disorders. Parents and children 2-18 years completed surveys at seven timepoints (April 2020 to June 2022). Parents completed validated measures of depression and anxiety for children 8-18 years, and validated measures of emotional/behavioural symptoms for children 2-7 years old; children ≥10 years completed validated measures of depression and anxiety. Latent growth curve analysis determined depression and anxiety trajectories, accounting for demographics, child and parent MH. Data were available on 1315 unique children (1259 parent-reports; 550 child-reports). Trajectories were stable across the study period, however individual variation in trajectories was statistically significant. Of included covariates, only initial symptom level predicted symptom trajectories. Among participants with pre-COVID data, a significant increase in depression symptoms relative to pre-pandemic levels was observed; children and adolescents experienced elevated and sustained levels of depression and anxiety during the two-year period. Findings have direct policy implications in the prioritization and of maintenance of educational, recreational, and social activities with added MH supports in the face of future events.

2.
bioRxiv ; 2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39071315

RESUMO

Cryo-EM and X-ray crystallography provide crucial experimental data for obtaining atomic-detail models of biomacromolecules. Refining these models relies on library- based stereochemical restraints, which, in addition to being limited to known chemical entities, do not include meaningful noncovalent interactions relying solely on nonbonded repulsions. Quantum mechanical (QM) calculations could alleviate these issues but are too expensive for large molecules. We present a novel AI-enabled Quantum Refinement (AQuaRef) based on AIMNet2 neural network potential mimicking QM at substantially lower computational costs. By refining 41 cryo-EM and 30 X-ray structures, we show that this approach yields atomic models with superior geometric quality compared to standard techniques, while maintaining an equal or better fit to experimental data.

3.
Contraception ; : 110550, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39067560

RESUMO

OBJECTIVE: To compare cervical preparation with transcervical balloon to osmotic dilators for second-trimester procedural abortions. STUDY DESIGN: We performed an unblinded, randomized, non-inferiority trial of people undergoing second-trimester procedural abortion at 18+0 to 23+6 weeks gestation. We randomized participants to either overnight osmotic dilators (Dilapan-S) or transcervical balloon (Foley). Both groups received overnight mifepristone and pre-procedural misoprostol. We powered the study on mean difference in procedure duration; non-inferiority limit 5 minutes. We compared pre-procedure cervical dilation; need for additional dilation; and, using 100-point visual analogue scale, measured physician satisfaction and ease of procedure, and participant pain and satisfaction. RESULTS: We recruited 32 participants at a single academic center. Although procedure time (minutes) was similar (balloon: 22.6+8.9 vs Dilapan-S: 22.4+12.8, p=0.96), non-inferiority was not met (mean difference, 0.2 minutes; 95% confidence interval, -7.8 to 8.2). Cervical dilation >2cm was more likely after Dilapan-S (100% vs 62.5%, p=0.02). Placement was well tolerated with similar time (minutes) for insertion (balloon: 4.8+1.0, Dilapan-S: 5.1+2.3, p=0.64) and maximum pain (median) with insertion (balloon 39 (5-78), Dilapan-S: 39 (0-100), p=0.92). Pain immediately post-insertion was higher for Dilapan-S (33 (0-100) vs 18 (0-50), p=0.046), and similar for maximum pain overnight, participant satisfaction, and likelihood to recommend. Complications were minor and similar between groups (p=0.60). CONCLUSION: While significantly more people with transcervical balloon required mechanical dilation, the difference in operative time was clinically negligible. The transcervical balloon was well tolerated and acceptable by participants. IMPLICATIONS: Clinicians experienced in mechanical dilation may consider a transcervical balloon as a lower-cost tool for second-trimester abortion cervical preparation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT05099991.

4.
Polymers (Basel) ; 16(14)2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39065397

RESUMO

Electrospinning is a widely employed manufacturing platform for tissue engineering applications because it produces structures that closely mimic the extracellular matrix. Herein, we demonstrate the potential of poly(vinyl alcohol) (PVA) electrospun nanofibers as scaffolds for tissue engineering. Nanofibers were created by needleless direct current electrospinning from PVA with two different degrees of hydrolysis (DH), namely 98% and 99% and subsequently heat treated at 180 °C for up to 16 h to render them insoluble in aqueous environments without the use of toxic cross-linking agents. Despite the small differences in the PVA chemical structure, the changes in the material properties were substantial. The higher degree of hydrolysis resulted in non-woven supports with thinner fibres (285 ± 81 nm c.f. 399 ± 153 nm) that were mechanically stronger by 62% (±11%) and almost twice as more crystalline than those from 98% hydrolysed PVA. Although prolonged heat treatment (16 h) did not influence fibre morphology, it reduced the crystallinity and tensile strength for both sets of materials. All samples demonstrated a lack or very low degree of haemolysis (<5%), and there were no notable changes in their anticoagulant activity (≤3%). Thrombus formation, on the other hand, increased by 82% (±18%) for the 98% hydrolysed samples and by 71% (±10%) for the 99% hydrolysed samples, with heat treatment up to 16 h, as a direct consequence of the preservation of the fibrous morphology. 3T3 mouse fibroblasts showed the best proliferation on scaffolds that were thermally stabilised for 4 and 8 h. Overall these scaffolds show potential as 'greener' alternatives to other electrospun tissue engineering materials, especially in cases where they may be used as delivery vectors for heat tolerant additives.

5.
J Biol Chem ; : 107602, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39059496

RESUMO

Glycosylation is a predominant strategy plants employ to fine-tune the properties of small molecule metabolites to affect their bioactivity, transport, and storage. It is also important in biotechnology and medicine as many glycosides are utilized in human health. Small molecule glycosylation is largely carried out by family 1 glycosyltransferases. Here, we report a structural and biochemical investigation of UGT95A1, a family 1 GT enzyme from Pilosella officinarum that exhibits a strong, unusual regiospecificity for the 3'-O position of flavonoid acceptor substrate luteolin. We obtained an apo crystal structure to help drive the analyses of a series of binding site mutants, revealing that while most residues are tolerant to mutations, key residues M145 and D464 are important for overall glycosylation activity. Interestingly, E347 is crucial for maintaining the strong preference for 3'-O glycosylation, while R462 can be mutated to increase regioselectivity. The structural determinants of regioselectivity were further confirmed in homologous enzymes. Our study also suggests that the enzyme contains large, highly dynamic, disordered regions. We showed that while most disordered regions of the protein have little to no implication in catalysis, the disordered regions conserved among investigated homologues are important to both the overall efficiency and regiospecificity of the enzyme. This report represents a comprehensive in-depth analysis of a family 1 GT enzyme with a unique substrate regiospecificity and may provide a basis for enzyme functional prediction and engineering.

6.
Clin Infect Dis ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39041385

RESUMO

Cytomegalovirus (CMV) infection and disease are important causes of morbidity and mortality in transplant recipients. For the purpose of developing consistent reporting of CMV outcomes in clinical trials, definitions of CMV infection and disease were developed and most recently published in 2017. Since then, there have been major developments, including registration of new antiviral agents. Therefore, the Transplant Associated Virus Infections Forum, which consists of scientists, clinicians, regulators, and industry representatives, has produced an updated version of these definitions that incorporates recent knowledge with the aim of supporting clinical research and drug development. This also includes an update regarding the definition of resistant and refractory CMV infections previously published in 2019. As the field evolves, the need for updates of these definitions is clear, and collaborative efforts among clinicians, scientists, regulators, and industry representatives can provide a platform for this work.

7.
Pediatr Pulmonol ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953717

RESUMO

BACKGROUND: Several techniques can be used to assess bronchodilator response (BDR) in preschool-aged children, including spirometry, respiratory oscillometry, the interrupter technique, and specific airway resistance. However, there has not been a systematic comparison of BDR thresholds across studies yet. METHODS: A systematic review was performed on all studies up to May 2023 measuring a bronchodilator effect in children 2-6 years old using one of these techniques (PROSPERO CRD42021264659). Studies were identified using MEDLINE, Cochrane, EMBASE, CINAHL via EBSCO, Web of Science databases, and reference lists of relevant manuscripts. RESULTS: Of 1224 screened studies, 43 were included. Over 85% were from predominantly European ancestry populations, and only 22 studies (51.2%) calculated a BDR cutoff based on a healthy control group. Five studies included triplicate testing with a placebo to account for the within-subject intrasession repeatability. A relative BDR was most consistently reported by the included studies (95%) but varied widely across all techniques. Various statistical methods were used to define a BDR, with six studies using receiver operating characteristic analyses to measure the discriminative power to distinguish healthy from wheezy and asthmatic children. CONCLUSION: A BDR in 2- to 6-year-olds cannot be universally defined based on the reviewed literature due to inconsistent methodology and cutoff calculations. Further studies incorporating robust methods using either distribution-based or clinical anchor-based approaches to define BDR are required.

8.
J Occup Environ Med ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38955811

RESUMO

OBJECTIVES: Paradoxical associations between high occupational physical activity (OPA) and cardiovascular disease may be explained by exaggerated cardiovascular responses from high work-related stress or low worker fitness. METHODS: OPA, blood pressure (BP), heart rate (HR), and rate-pressure product (HR x BP, RPP) were measured objectively for 24-hours in nineteen male workers. Work-related stress was measured using the Stress-in-General Scale. Fitness was estimated using a submaximal treadmill test. Effect modification by work-related stress and fitness on associations between OPA and cardiovascular responses was examined using mixed models with interactions. RESULTS: Associations between OPA and RPP, HR, and BP were stronger with high stress (p < 0.05). Associations of work-time MVPA and RPP were attenuated with higher fitness (p < 0.05). CONCLUSIONS: OPA performed under high work-related stress or by workers with low fitness may exaggerate cardiovascular responses to OPA.

9.
Health Aff (Millwood) ; 43(7): 942-949, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38950298

RESUMO

There is widespread agreement that taxpayers pay more when Medicare beneficiaries are enrolled in Medicare Advantage (MA) plans than if those beneficiaries were enrolled in traditional Medicare. MA plans are paid on the basis of submitted diagnoses and thus have a clear incentive to encourage providers to find and report as many diagnoses for their enrollees as possible. Two mechanisms that MA plans use to identify diagnoses that are not available for beneficiaries in traditional Medicare are in-home health risk assessments and chart reviews. Using MA encounter data for 2015-20, I isolated the impact of these two types of encounters on the risk scores used for payments to MA plans during 2016-21. I found that encounter-based risk scores for MA enrollees were higher by 0.091 points, or 7.4 percent, in 2021 when in-home health risk assessments and chart reviews were included than they would have been without the use of these tools.


Assuntos
Medicare Part C , Humanos , Estados Unidos , Medição de Risco , Idoso , Masculino , Feminino , Idoso de 80 Anos ou mais , Codificação Clínica , Serviços de Assistência Domiciliar/economia
10.
Neurosurg Focus ; 57(1): E9, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38950448

RESUMO

OBJECTIVE: Prior studies have investigated associations between gender, symptom resolution, and time to return to play following sport-related concussion (SRC). However, there is a notable gap in research regarding the association between gender and return to learn (RTL) in adolescents. Therefore, this study 1) compared the patterns of RTL between boys and girls who are high school student athletes, and 2) evaluated the possible association between gender and time to RTL after adjusting for covariates. METHODS: A retrospective cohort study of a prospective surveillance program that monitored concussion recovery of athletes in high schools throughout the state of Maine between February 2015 and January 2023 was performed. The primary independent variable was gender, dichotomized as boys and girls. The primary outcome was time to RTL, defined by the number of days for an athlete to return to school without accommodations. Mann-Whitney U-tests were used to compare RTL between the boys and girls. Each athlete's RTL status was dichotomized (i.e., returned vs had not returned) at several time points following injury (i.e., 1, 2, 3, and 4 weeks), and chi-square tests were performed to compare the proportions who achieved RTL between groups. Multivariable linear regression analyses were performed to evaluate the predictive value of gender on RTL. Covariates included age, number of previous concussions, history of learning disability or attention-deficit disorder or attention-deficit/hyperactivity disorder, history of a psychological condition, history of headaches or migraines, initial Sport Concussion Assessment Tool (SCAT3/SCAT5) score, and days to evaluation. RESULTS: Of 895 high school athletes, 488 (54.5%) were boys and 407 (45.5%) were girls. There was no statistically significant difference in median [IQR] days to RTL between genders (6.0 [3.0-11.0] vs 6.0 [3.0-12.0] days; U = 84,365.00, p < 0.375). A greater proportion of boys successfully returned to learn without accommodations by 3 weeks following concussion (93.5% vs 89.4%; χ2 = 4.68, p = 0.030), but no differences were found at 1, 2, or 4 weeks. A multivariable model predicting days to RTL showed that gender was not a significant predictor of RTL (p > 0.05). Longer days to evaluation (ß = 0.10, p = 0.021) and higher initial SCAT3/SCAT5 scores (ß = 0.15, p < 0.001) predicted longer RTL. CONCLUSIONS: In a cohort of high school athletes, RTL did not differ between boys and girls following SRC. Gender was not a significant predictor of RTL. Longer days to evaluation and higher initial symptom scores were associated with longer RTL.


Assuntos
Atletas , Traumatismos em Atletas , Concussão Encefálica , Estudantes , Humanos , Masculino , Feminino , Concussão Encefálica/epidemiologia , Adolescente , Traumatismos em Atletas/epidemiologia , Estudos Retrospectivos , Caracteres Sexuais , Recuperação de Função Fisiológica/fisiologia , Fatores Sexuais , Aprendizagem/fisiologia , Estudos de Coortes , Estudos Prospectivos , Instituições Acadêmicas , Retorno à Escola , Volta ao Esporte
11.
J Anesth Analg Crit Care ; 4(1): 39, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956707

RESUMO

BACKGROUND: Pancreatic surgery is associated with a significant risk for acute kidney injury (AKI) and clinically relevant postoperative pancreatic fistula (CR-POPF). This investigation evaluated the impact of intraoperative volume administration, vasopressor therapy, and blood pressure management on the primary outcome of AKI and the secondary outcome of a CR-POPF after pancreatic surgery. METHODS: This retrospective single-center cohort investigated 200 consecutive pancreatic surgeries (January 2018-December 2021). Patients were categorized for the presence/absence of AKI (Kidney Disease Improving Global Outcomes) and CR-POPF. After univariate analysis, multivariable models were constructed to control for the univariate cofactor differences in the primary and secondary outcomes. RESULTS: AKI was identified in 20 patients (10%) with significant univariate differences in demographics (body mass index and gender), comorbidities, indices of chronic renal insufficiency, and an increased AKI Risk score. Surgical characteristics, intraoperative fluid, vasopressor, and blood pressure management were similar in patients with and without AKI. Patients with AKI had increased blood loss, lower urine output, and packed red blood cell administration. After multivariate analysis, male gender (OR = 7.9, 95% C.I. 1.8-35.1) and the AKI Risk score (OR = 6.3, 95% C.I. 2.4-16.4) were associated with the development of AKI (p < 0.001). Intraoperative and postoperative volume, vasopressor administration, and intraoperative hypotension had no significant impact in the multivariate analysis. CR-POPF occurred in 23 patients (11.9%) with no significant contributing factors in the multivariate analysis. Patients who developed AKI or a CR-POPF had an increase in surgical complications, length of stay, discharge to a skilled nursing facility, and mortality. CONCLUSION: In this analysis, intraoperative volume administration, vasopressor therapy, and a blood pressure < 55 mmHg for more than 10 min were not associated with an increased risk of AKI. After multivariate analysis, male gender and an elevated AKI Risk score were associated with an increased likelihood of AKI.

12.
J Plant Physiol ; 301: 154303, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38959754

RESUMO

Cassava (Manihot esculenta Crantz) produces edible roots, a major carbohydrate source feeding more than 800 million people in Africa, Latin America, Oceania and Asia. Post-harvest physiological deterioration (PPD) renders harvested cassava roots unpalatable and unmarketable. Decades of research on PPD have elucidated several genetic, enzymatic and metabolic processes involved. Breeding populations were established to enable verification of robust biomarkers for PPD resistance. For comparison, these PPD populations have been cultivated concurrently with diversity population for carotenoid (ß-carotene) content. Results highlighted a significant variation of the chemotypes due to environmental factors. Less than 3% of the detected molecular features showed consistent trends between the two harvest years and were putatively identified as phenylpropanoid derived compounds (e.g. caffeoyl rutinoside). The data corroborated that ∼20 µg ß-carotene/g DW can reduced the PPD response of the cassava roots to a score of ∼1. Correlation analysis showed a significant correlation of ß-carotene content at harvest to PPD response (R2 -0.55). However, the decrease of ß-carotene over storage was not significantly correlated to initial content or PPD response. Volatile analysis observed changes of apocarotenoids derived from ß-carotene, lipid oxidation products (alkanes, alcohols and carbonyls and esters) and terpenes. The majority of these volatiles (>90%) showed no significant correlation to ß-carotene or PPD. Observed data indicated an increase (∼2-fold) of alkanes in varieties with ß-carotene >10 µg/g DW and a decrease (∼60%) in varieties with less ß-carotene. Fatty acid methyl esters with a chain length > C9 were detected solely after storage and show lower levels in varieties with higher ß-carotene content. In combination with correlation values to PPD (R2 ∼0.3; P-value >0.05), the data indicated a more efficient ROS quenching mechanism in PPD resistant varieties.

14.
Respir Res ; 25(1): 269, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38982492

RESUMO

BACKGROUND: Cystic Fibrosis causing mutations in the gene CFTR, reduce the activity of the CFTR channel protein, and leads to mucus aggregation, airway obstruction and poor lung function. A role for CFTR in the pathogenesis of other muco-obstructive airway diseases such as Chronic Obstructive Pulmonary Disease (COPD) has been well established. The CFTR modulatory compound, Ivacaftor (VX-770), potentiates channel activity of CFTR and certain CF-causing mutations and has been shown to ameliorate mucus obstruction and improve lung function in people harbouring these CF-causing mutations. A pilot trial of Ivacaftor supported its potential efficacy for the treatment of mucus obstruction in COPD. These findings prompted the search for CFTR potentiators that are more effective in ameliorating cigarette-smoke (CS) induced mucostasis. METHODS: Small molecule potentiators, previously identified in CFTR binding studies, were tested for activity in augmenting CFTR channel activity using patch clamp electrophysiology in HEK-293 cells, a fluorescence-based assay of membrane potential in Calu-3 cells and in Ussing chamber studies of primary bronchial epithelial cultures. Addition of cigarette smoke extract (CSE) to the solutions bathing the apical surface of Calu-3 cells and primary bronchial airway cultures was used to model COPD. Confocal studies of the velocity of fluorescent microsphere movement on the apical surface of CSE exposed airway epithelial cultures, were used to assess the effect of potentiators on CFTR-mediated mucociliary movement. RESULTS: We showed that SK-POT1, like VX-770, was effective in augmenting the cyclic AMP-dependent channel activity of CFTR. SK-POT-1 enhanced CFTR channel activity in airway epithelial cells previously exposed to CSE and ameliorated mucostasis on the surface of primary airway cultures. CONCLUSION: Together, this evidence supports the further development of SK-POT1 as an intervention in the treatment of COPD.


Assuntos
Aminofenóis , Brônquios , Regulador de Condutância Transmembrana em Fibrose Cística , Células Epiteliais , Quinolonas , Humanos , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Quinolonas/farmacologia , Aminofenóis/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Brônquios/efeitos dos fármacos , Brônquios/metabolismo , Fumaça/efeitos adversos , Células Cultivadas , Células HEK293 , Agonistas dos Canais de Cloreto/farmacologia , Agonistas dos Canais de Cloreto/uso terapêutico , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo
15.
Artigo em Inglês | MEDLINE | ID: mdl-38988191

RESUMO

BACKGROUND: Although formal preparedness for unexpected crises has long been a concern of health care policy and delivery, many hospitals struggled to manage staff and equipment shortages, precarious finances, and supply chain disruptions among other difficulties during the COVID-19 pandemic. Our purpose was to analyze how hospitals used formal and informal emergency management practices to maintain safe and high-quality care while responding to crisis. METHODS: We conducted a qualitative study based on 26 interviews with hospital leaders and emergency managers from 12 U.S. hospitals purposively sampled to vary along geographic location, urban/rural delineation, size, resource availability, system membership, teaching status, and performance levels among other characteristics. RESULTS: In order to manage staff, space, supplies, and systems related challenges, hospitals engaged formal and informal practices around planning, teaming, and exchanging resources and information.Relying solely only on formal or informal practices proved inadequate, especially when prespecified plans, the incident command structure, and existing contracts and communication platforms failed to support resilient response. We identified emergent capabilities - imaginative planning, recombinant teaming, and transformational exchange - through which hospitals achieved harmonious interplay between the formal and informal practices of emergency management that supported safe care and resilience amid crisis. CONCLUSION: Managing emergent challenges for and amid crisis calls for health care delivery organizations to engage creative planning processes, enable motivated workers with diverse skill sets to team up, and establish rich inter- and intra-organizational partnerships that support vital exchange.

16.
Am J Surg ; : 115823, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38981838

RESUMO

BACKGROUND: Zenker's diverticulum (ZD) was historically treated with an open transcervical myotomy with diverticulectomy, but endoscopic approaches have gained popularity, though with little recent data. This study aimed to report flexible endoscopic cricopharyngomyotomy (FEC) outcomes, particularly in smaller diverticula. METHODS: Patients with ZD treated with FEC at a tertiary center were reviewed. Patients were grouped by diverticulum size: small (sZD)≤1.5 â€‹cm; medium (mZD) â€‹> â€‹1.5 â€‹cm. RESULTS: Of 30 patients, median age, BMI, sex, and comorbidities were similar between sZD (n â€‹= â€‹18) and mZD (n â€‹= â€‹12). Overall, 80.0 â€‹% had the procedure performed with a needle knife. Median number of clips for mucosotomy closure (5.0[5.0,6.0]vs.7.0[5.0,7.0]clips;p â€‹= â€‹0.051), operative time (59.5[51.0,75.0]vs.74.5[51.0,93.5]minutes;p â€‹= â€‹0.498), length-of-stay (1.0[1.0,1.0]vs.1.0[1.0,1.0]days;p â€‹= â€‹0.397), and follow-up (20.8[1.1,33.4]vs.15.6[5.4,50.4]months;p â€‹= â€‹0.641) were comparable. There were no postoperative leaks; incomplete myotomy occurred in one sZD, yielding a clinical success rate of 96.7 â€‹%. CONCLUSIONS: FEC has a high success rate for ZD and an advantage in small diverticula, difficult to treat with stapling or open technique.

17.
Cardiol Ther ; 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39003659

RESUMO

INTRODUCTION: The prevalence of tendon rupture and tendinopathies (TRT) has not been determined in a large population of patients with atherosclerotic cardiovascular disease (ASCVD). We investigated TRT prevalence among patients with ASCVD and in the general population, using data from the Symphony Health Integrated Dataverse, a large US medical and pharmacy claims database. METHODS: This retrospective, observational study included patients aged ≥ 19 years from the claims database during the identification period (January 2019 to December 2020) and 12 months of continuous enrollment. The primary outcome was evidence of TRT in the 12 months following the index date (first ASCVD diagnosis in the ASCVD cohort; first claim in the claims database in the overall population). Diagnostic codes (ICD-10 and/or CPT) were used to define ASCVD and TRT diagnosis. RESULTS: The ASCVD cohort and overall population included 5,589,273 and 61,715,843 patients, respectively. In the ASCVD cohort, use of medications with a potential or known association with TRT was identified in 67.9% (statins), 17.7% (corticosteroids), and 16.7% (fluoroquinolones) of patients. Bempedoic acid use was reported in 1556 (< 0.1%) patients. TRT prevalence during 12-month follow-up was 3.4% (ASCVD cohort) and 1.9% (overall population). Among patients with ASCVD, 83.5% experienced TRT in only one region of the body. Factors most associated with TRT in the ASCVD cohort were increasing age, most notably in those aged 45-|64 years (odds ratio [OR] 2.19; 95% confidence interval [CI] 2.07-2.32), obesity (OR 1.51; 95% CI 1.50-1.53), and rheumatoid arthritis (OR 1.47; 95% CI 1.45-1.79). Use of statins or bempedoic acid was not associated with increased TRT risk. CONCLUSION: Patients with ASCVD may have greater risk of TRT than the general population, which may be driven by an increased prevalence of comorbidities and use of medications with a potential or known association with TRT.


Patients with atherosclerosis, the main cause of heart attacks, strokes, and peripheral vascular disease, typically require several drugs to control the disease. Some of the drugs used to treat atherosclerosis have been linked to a higher occurrence of tendon tears (or ruptures) or swelling/inflammation of the tendons (tendinopathies). However, there may be other factors present in these patients that increase the risk of tendon injuries that are not related to these drugs. This study used the medical records of over 5.5 million patients with atherosclerosis and over 63 million patients reflecting the general population in the United States to determine the prevalence of tendon injury. Additionally, the researchers looked at other factors that might be related to a higher risk of tendon injury in each group. Over a 12-month period, tendon injuries occurred in 3.4% of patients with atherosclerosis and 1.8% of patients in the general population. In patients with atherosclerosis, factors such as being obese, older (45­64 years), or having rheumatoid arthritis were also linked to an increased risk of tendon injuries. There was no association seen between statin or bempedoic acid use and tendon injuries. These results may help healthcare providers to determine the underlying risk of tendon injuries and guide treatment of this patient population.

18.
Sci Rep ; 14(1): 16055, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992196

RESUMO

Immunological adaptions during pregnancy play a crucial role in healthy fetal development. Aberrant immune modifications however contribute to adverse pregnancy outcomes, which may be driven by maternal factors such as previous pregnancies and BMI. This secondary analysis of the MicrobeMom2 RCT investigates the changes to maternal inflammatory biomarkers derived from serum and stimulated peripheral blood mononuclear cells (PBMCs) during pregnancy, and the effects of previous pregnancies (parity) and BMI on maternal immune responses. Changes in immune and metabolic biomarkers from early (11-15 weeks' gestation) to late (28-32 weeks' gestation) pregnancy were compared using paired t-tests. Participants were then split by parity (nulliparous, parous) and BMI (BMI < 25, BMI > = 25), and the relationship between parity and BMI with immune biomarker levels was examined using independent t-tests, paired t-tests, ANCOVA, and linear regression. Equivalent non-parametric tests were used for skewed data. Recruited women (n = 72) were on average 31.17 (SD ± 4.53) years of age and 25.11 (SD ± 3.82) BMI (kg/m2). Of these, 51 (70.8%) had a previous term pregnancy. Throughout gestation, PBMC cytokines displayed contrasting trends to serum, with a dampening of immune responses noted in PBMCs, and enhanced production of cytokines observed in the serum. Significant decreases in PBMC derived TNF-α, IL-10 and IFN-γ were seen from early to late pregnancy. Serum C3, IL-17A, IL-6, TNF-α, CD163, GDF-15 and leptin increased throughout gestation. First pregnancy was associated with higher levels of leptin in late pregnancy, while parous women showed significant decreases in PBMC derived TNF-α, IL10, and IFN-γ with gestation. Differences in levels of C3, IL-17A, TNF-α, GDF-15 and leptin were observed across BMI groups. Overall, serum-derived cytokines exhibit contrasting levels to those derived from stimulated PBMCs. Maternal immune responses undergo significant changes from early to late pregnancy, which are influenced by parity and BMI. These differences aid our understanding as to why first-time mothers are at greater risk of placental disease such as pre-eclampsia and fetal growth restriction.


Assuntos
Biomarcadores , Índice de Massa Corporal , Leucócitos Mononucleares , Humanos , Feminino , Gravidez , Adulto , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Biomarcadores/sangue , Paridade , Citocinas/sangue
19.
IUCrdata ; 9(Pt 6): x240612, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38974847

RESUMO

The crystal structure of the title compound was determined at 120 K. It crystallizes in the triclinic space group P with four independent mol-ecules in the asymmetric unit. In the crystal, each symmetry-unique mol-ecule forms π-π stacks on itself, giving four unique π-π stacking inter-actions. Inter-molecular hydrogen bonding is observed between each pair of independent mol-ecules, where each hy-droxy group can act as a hydrogen-bond donor and acceptor.

20.
QJM ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976637

RESUMO

INTRODUCTION: Spontaneous pneumothorax recurs in 30 to 54% of patients without surgery. Identifying individuals likely to suffer a recurrence, who might benefit from pre-emptive surgery, is challenging. Previous meta-analysis suggested a relationship between contralateral recurrence and specific computed tomography (CT) findings. METHODS: We analysed CT images and recurrence rates 243 patients seen by our tertiary referral pneumothorax service. RESULTS: We validated the meta-analysis observation that contralateral lung cysts are associated with a higher risk of contralateral recurrence in younger individuals. Furthermore, we observed the size of contralateral cysts to be associated with increased contralateral recurrence in younger patients. CONCLUSION: The detection of contralateral lung cysts might therefore help identify younger patients more likely to benefit from pre-emptive surgery.

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