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1.
Curr Dev Nutr ; 8(6): 103778, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38952351

RESUMO

Background: Fruits and vegetables (FV) are a critical source of nutrients, yet children in the United States are not meeting the Dietary Guidelines for Americans (DGA). The monthly FV cash value benefit (CVB) included in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)'s food package to support child FV intake (FVI) received a substantial increase for economic relief during the COVID-19 pandemic. Objectives: To evaluate how an expansion of the monthly WIC CVB to purchase FV for WIC children ages 1-4 y is associated with diversity in FV redeemed, and how changes in redeemed FV are related to FVI. Methods: Caregivers representing 1463 WIC-participating children recruited from Los Angeles County, California, completed surveys during the CVB augmentation (T1: CVB = $9/mo; T2 = $35/mo; T3 = $24/mo). Redeemed price look-up codes (PLUs), corresponding to a food item, were assigned to its corresponding MyPlate FV group. Multivariable generalized estimating equation regression models assessed changes in amount and diversity of FV redemption across MyPlate groups and associations between changes in FV diversity and changes in FVI. Results: Slightly over half of all households were food insecure (55%), half of the children were female (52%), and most were Hispanic (78%). Compared with T1, significant increases in the number of PLUs and dollars redeemed were observed in most MyPlate FV groups. From T1 to T2, significant increases in diversity scores were observed for total fruit (ß: 1.6 pts; 95% confidence interval [CI]: 1.4, 1.7), total vegetable (ß: 3.6 pts; 95%CI: 3.4, 3.9), and total FV (ß:7.8 pts; 95%CI: 7.4, 8.2). Similarly, increases in diversity score were observed at T3 compared with T1. Changes in FV diversity redeemed were not associated with changes in FVI. Conclusions: During the CVB augmentation, WIC participants redeemed a greater amount and variety of FV according to DGA MyPlate recommendations, supporting its permanent increase.

2.
Arthroplast Today ; 28: 101398, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38993836

RESUMO

Background: Hip dysplasia is considered one of the leading etiologies contributing to hip degeneration and the eventual need for total hip arthroplasty (THA). We validated a deep learning (DL) algorithm to measure angles relevant to hip dysplasia and applied this algorithm to determine the prevalence of dysplasia in a large population based on incremental radiographic cutoffs. Methods: Patients from the Osteoarthritis Initiative with anteroposterior pelvis radiographs and without previous THAs were included. A DL algorithm automated 3 angles associated with hip dysplasia: modified lateral center-edge angle (LCEA), Tönnis angle, and modified Sharp angle. The algorithm was validated against manual measurements, and all angles were measured in a cohort of 3869 patients (61.2 ± 9.2 years, 57.1% female). The percentile distributions and prevalence of dysplastic hips were analyzed using each angle. Results: The algorithm had no significant difference (P > .05) in measurements (paired difference: 0.3°-0.7°) against readers and had excellent agreement for dysplasia classification (kappa = 0.78-0.88). In 140 minutes, 23,214 measurements were automated for 3869 patients. LCEA and Sharp angles were higher and the Tönnis angle was lower (P < .01) in females. The dysplastic hip prevalence varied from 2.5% to 20% utilizing the following cutoffs: 17.3°-25.5° (LCEA), 9.4°-15.6° (Tönnis), and 41.3°-45.9° (Sharp). Conclusions: A DL algorithm was developed to measure and classify hips with mild hip dysplasia. The reported prevalence of dysplasia in a large patient cohort was dependent on both the measurement and threshold, with 12.4% of patients having dysplasia radiographic indices indicative of higher THA risk.

4.
Nature ; 631(8019): 207-215, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38926576

RESUMO

Pyroptosis is a lytic cell death mode that helps limit the spread of infections and is also linked to pathology in sterile inflammatory diseases and autoimmune diseases1-4. During pyroptosis, inflammasome activation and the engagement of caspase-1 lead to cell death, along with the maturation and secretion of the inflammatory cytokine interleukin-1ß (IL-1ß). The dominant effect of IL-1ß in promoting tissue inflammation has clouded the potential influence of other factors released from pyroptotic cells. Here, using a system in which macrophages are induced to undergo pyroptosis without IL-1ß or IL-1α release (denoted Pyro-1), we identify unexpected beneficial effects of the Pyro-1 secretome. First, we noted that the Pyro-1 supernatants upregulated gene signatures linked to migration, cellular proliferation and wound healing. Consistent with this gene signature, Pyro-1 supernatants boosted migration of primary fibroblasts and macrophages, and promoted faster wound closure in vitro and improved tissue repair in vivo. In mechanistic studies, lipidomics and metabolomics of the Pyro-1 supernatants identified the presence of both oxylipins and metabolites, linking them to pro-wound-healing effects. Focusing specifically on the oxylipin prostaglandin E2 (PGE2), we find that its synthesis is induced de novo during pyroptosis, downstream of caspase-1 activation and cyclooxygenase-2 activity; further, PGE2 synthesis occurs late in pyroptosis, with its release dependent on gasdermin D pores opened during pyroptosis. As for the pyroptotic metabolites, they link to immune cell infiltration into the wounds, and polarization to CD301+ macrophages. Collectively, these data advance the concept that the pyroptotic secretome possesses oxylipins and metabolites with tissue repair properties that may be harnessed therapeutically.


Assuntos
Macrófagos , Oxilipinas , Piroptose , Secretoma , Cicatrização , Animais , Feminino , Humanos , Camundongos , Caspase 1/metabolismo , Movimento Celular , Proliferação de Células , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/biossíntese , Dinoprostona/metabolismo , Fibroblastos/metabolismo , Fibroblastos/citologia , Gasderminas/metabolismo , Inflamassomos/metabolismo , Interleucina-1beta , Lipidômica , Macrófagos/metabolismo , Macrófagos/citologia , Camundongos Endogâmicos C57BL , Oxilipinas/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Secretoma/metabolismo , Cicatrização/fisiologia
5.
Headache ; 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38923523

RESUMO

OBJECTIVE: To apply the 2019 joint American Academy of Neurology (AAN) and American Headache Society (AHS) quality measures for headache management to a cohort of neurology resident physicians and then assess outcomes related to guideline adherence. BACKGROUND: The optimization of headache management is essential to reduce both the individual and systemic impact of these disorders. In 2014, the AAN developed 10 quality measures for evidence-based management of patients with headache. A workgroup updated and condensed its headache quality measures in 2019, narrowing the set to six measurements, four of which would primarily focus on the management of migraine and two of which would address the management of cluster headache. METHODS: This quality improvement study was conducted using a pretest-posttest study design. A pre-intervention survey based on retrospective analysis of five clinic notes for adherence to the measures was designed and distributed to all neurology residents (n = 32) at a large, academic tertiary referral center. The intervention included the creation of an electronic medical record template to aid residents in following the measures during clinical encounters, as well as the provision of direct feedback based on pre-intervention results. Finally, a post-intervention survey was distributed for completion based on notes written during the intervention period. Analysis was limited to migraine, given the low percentage of cluster headache seen in clinic. RESULTS: An increase in adherence was seen in three of the four migraine-related quality measures, with the Use of Abortive Medications for Migraine and Documentation of Counseling on Modifiable Lifestyle and Chronification Factors demonstrating statistically significant improvements (75.8% to 88.0% [p = 0.013] and 83.9% to 94.0% [p = 0.029] adherence, respectively). For secondary outcomes, the increase in the utilization of appropriate diagnostic criteria (82.6% to 93.2%, p = 0.018) was significant, and the self-assessed confidence rating for adherence to guidelines was significant (p < 0.001). CONCLUSIONS: This study provides evidence that the quality improvement intervention led to increased adherence to the AAN and AHS migraine-related measures. It is anticipated that increased adherence may lead to improved patient outcomes.

6.
Am J Clin Nutr ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38852854

RESUMO

BACKGROUND: The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) provides supplemental healthy foods to children aged <5 y in low-income households. OBJECTIVES: The objectives of this study were to characterize WIC benefit redemption, identify associations between benefit redemption and child dietary intake, and whether child age modifies these associations. METHODS: The cross-sectional 2023 California Statewide WIC Survey, conducted with caregivers of WIC-participating children aged 1-4 y, was analyzed for this study. Included children had complete benefit redemption data, a complete National Health and Nutrition Examination Survey Dietary Screener Questionnaire (DSQ), and complete covariate data (weighted n = 2244). Monthly household category-specific benefit redemption percentage was averaged across 6 and 3 mo preceding survey completion. Associations between household redemption and child dietary intake (servings or amount/day) were assessed with multivariable linear regression and expressed as estimates and 95% confidence intervals (CI). RESULTS: Twenty-five percent higher redemption of breakfast cereal, whole grain bread, yogurt and whole milk in the 6 mo prior to the survey were associated with higher child intake frequency for cereal (0.02 servings/d; 95% CI: 0.00, 0.04), whole grain bread (0.02 servings/d; 95% CI: 0.00, 0.03), yogurt (0.04 servings/d; 95% CI: 0.02, 0.06), and whole milk (0.09 servings/d; 95% CI: 0.01, 0.16). Significant effect modification by child age (12 to <24 mo, 24-59 mo) was found for redemption of cheese/tofu and 100% juice (P-interaction = 0.02 and 0.001, respectively), and 25% higher redemption of these benefits were associated with lower intake frequency for cheese (-0.05 servings/d; 95% CI: -0.09, -0.02) and higher intake frequency for juice (0.12 servings/d; 95% CI: 0.06, 0.18), but only among children ages 12 to <24 mo. CONCLUSIONS: Higher redemption was associated with higher child intake of select WIC foods. Pairing the promotion of benefit redemption among program participants with nutrition education efforts may enhance dietary impacts of WIC participation.

7.
Urol Pract ; 11(4): 761-768, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38899654

RESUMO

INTRODUCTION: Since the integration of the intern year into urology residencies, programs are mandated to introduce fundamental skills to junior residents. Our goal was to assess the impact of one such program: the 2023 New York Section of the AUA (NYS-AUA) EMPIRE (Educational Multi-institutional Program for Instructing REsidents) Boot Camp. METHODS: Junior urology residents from all 10 NYS-AUA institutions attended a free EMPIRE Boot Camp on June 9, 2023. The seminar covered procedural skills including urethral catheterization, cystoscopy, renal and bladder ultrasound, transrectal prostate ultrasound with biopsy, and an introduction to robotics/laparoscopy. Sessions focused on urologic emergencies and postoperative scenarios. Participants completed questionnaires before, immediately after, and 6 months post course, assessing comfort with procedures and overall program quality using a 5-point Likert scale and free text responses. t Tests compared pre and immediate/6-month post scores. RESULTS: Forty junior residents, along with faculty and resident instructors from all 10 NYS-AUA programs, participated. Of the 40 trainees, 35 (87.5%) completed pre- and immediate post-boot camp surveys, while 23 (57.5%) responded to the 6-month follow-up survey. Ratings showed significant improvement in comfort with basic urologic technical skills for 13 out of 14 domains (93%) immediately after the course and at the 6-month mark. Attendees reported notably higher comfort levels in managing obstructive pyelonephritis (P = .003) and postoperative complications (P = .001) following didactic sessions. CONCLUSIONS: A skills-based, free collaborative urology boot camp for junior residents is feasible and can be effective. Trainees reported improved comfort performing certain technical skills and managing urologic emergencies both immediately after the course and at 6 months of follow-up.


Assuntos
Competência Clínica , Internato e Residência , Treinamento por Simulação , Urologia , Humanos , Urologia/educação , Treinamento por Simulação/métodos , Projetos Piloto , Procedimentos Cirúrgicos Urológicos/educação , New York , Masculino
8.
Urol Pract ; 11(4): 700-707, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38899660

RESUMO

INTRODUCTION: Radiation cystitis with hematuria (RCH) is a potentially devastating complication after pelvic radiation. The cumulative incidence of RCH is debated, and certain severe manifestations may require hospital admission. We aimed to evaluate demographics and outcomes of patients hospitalized for RCH. METHODS: We performed a retrospective review of hospitalized patients with a primary or secondary diagnosis of RCH from 2016 to 2019 using the National Inpatient Sample. Our unit of analysis was inpatient encounters. Our primary outcome was inpatient mortality. Secondary outcomes included need for inpatient procedures, transfusion, length of stay (LOS), and cost of admission. We then performed multivariate analysis using either a logistic or linear regression to identify predictors of mortality and LOS. Cost was analyzed using a generalized linear model controlling for LOS. RESULTS: We identified 21,320 weighted cases of hospitalized patients with RCH. The average patient age was 75.4 years, with 84.7% male and 69.3% White. The median LOS was 4 days, and the median cost was $8767. The inpatient mortality rate was 1.3%. The only significant predictor for mortality was older age. The only significant predictor of both higher cost and longer LOS was an Elixhauser Comorbidity Score ≥ 3. CONCLUSIONS: RCH represents a significant burden to patients and the health care system, and we observed an increasing number of hospitalized patients over time. Additional research is needed to identify underlying causes of RCH and effective treatments for this sometimes-severe complication of pelvic radiation.


Assuntos
Cistite , Lesões por Radiação , Humanos , Masculino , Feminino , Cistite/epidemiologia , Cistite/etiologia , Cistite/economia , Cistite/mortalidade , Idoso , Estudos Retrospectivos , Lesões por Radiação/epidemiologia , Lesões por Radiação/mortalidade , Lesões por Radiação/economia , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Hospitalização/estatística & dados numéricos , Hospitalização/economia , Idoso de 80 Anos ou mais , Pacientes Internados/estatística & dados numéricos , Tempo de Internação , Radioterapia/efeitos adversos , Radioterapia/economia , Hematúria/epidemiologia , Hematúria/etiologia
9.
Eur Stroke J ; : 23969873241260154, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38880882

RESUMO

BACKGROUND: Predicting functional impairment after intracerebral hemorrhage (ICH) provides valuable information for planning of patient care and rehabilitation strategies. Current prognostic tools are limited in making long term predictions and require multiple expert-defined inputs and interpretation that make their clinical implementation challenging. This study aimed to predict long term functional impairment of ICH patients from admission non-contrast CT scans, leveraging deep learning models in a survival analysis framework. METHODS: We used the admission non-contrast CT scans from 882 patients from the Massachusetts General Hospital ICH Study for training, hyperparameter optimization, and model selection, and 146 patients from the Yale New Haven ICH Study for external validation of a deep learning model predicting functional outcome. Disability (modified Rankin scale [mRS] > 2), severe disability (mRS > 4), and dependent living status were assessed via telephone interviews after 6, 12, and 24 months. The prediction methods were evaluated by the c-index and compared with ICH score and FUNC score. RESULTS: Using non-contrast CT, our deep learning model achieved higher prediction accuracy of post-ICH dependent living, disability, and severe disability by 6, 12, and 24 months (c-index 0.742 [95% CI -0.700 to 0.778], 0.712 [95% CI -0.674 to 0.752], 0.779 [95% CI -0.733 to 0.832] respectively) compared with the ICH score (c-index 0.673 [95% CI -0.662 to 0.688], 0.647 [95% CI -0.637 to 0.661] and 0.697 [95% CI -0.675 to 0.717]) and FUNC score (c-index 0.701 [95% CI- 0.698 to 0.723], 0.668 [95% CI -0.657 to 0.680] and 0.727 [95% CI -0.708 to 0.753]). In the external independent Yale-ICH cohort, similar performance metrics were obtained for disability and severe disability (c-index 0.725 [95% CI -0.673 to 0.781] and 0.747 [95% CI -0.676 to 0.807], respectively). Similar AUC of predicting each outcome at 6 months, 1 and 2 years after ICH was achieved compared with ICH score and FUNC score. CONCLUSION: We developed a generalizable deep learning model to predict onset of dependent living and disability after ICH, which could help to guide treatment decisions, advise relatives in the acute setting, optimize rehabilitation strategies, and anticipate long-term care needs.

10.
11.
J Anim Sci ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38902915

RESUMO

Isoacids are branched ketoacids which when fed to ruminants have been shown to enhance the growth of fiber-digesting organisms. Ninety finishing gilts were individually fed dietary treatments consisting of diet type: corn-soybean meal (CSBM), a diet containing 40% distillers dried grains with solubles (DDGS), or a diet containing 40% sugar beet pulp (SBP); in combination with either no feed additive (CNT), the addition of 0.50% isobutyrate (IB), or the addition of a 0.88% mix of isobutyrate, isovalerate, and 2-methylbutyrate (MX). Gilts consumed an average of 2.171 kg/d over the 28-d trial. On d 26, fresh fecal samples were collected for determination of apparent total tract digestibility (ATTD) of gross energy (GE) and nitrogen (N), determination of fecal volatile fatty acids (VFA), and evaluation of microbial ecology. There was no interaction between diet type and isoacid addition, and no main effect of isoacid or diet type on alpha or Shannon microbial diversity measures (P > 0.05). There was no interaction between isoacid addition and diet type, and no main effect of isoacid addition on microbial beta diversity (P > 0.05), but differences were observed in microbial beta diversity due to diet type (P ≤ 0.05). There was no interaction between diet type and isoacid addition observed in fecal VFA concentrations (P > 0.05), with only minor differences in fecal VFA concentrations noted due to isoacid addition (P ≤ 0.05). The interaction between diet type and isoacid addition on ATTD of dietary GE and N (P ≤ 0.01) was largely because the addition of IB did not affect ATTD of GE or N in pigs fed the CSBM diet, but increased ATTD of GE and N in pigs fed diets containing DDGS and decreased the ATTD of GE and N in pigs fed diets containing SBP. In contrast, adding a blend of isoacids (i.e., MX) reduced the ATTD of GE and N, regardless of diet type. There was no interaction between diet type and isoacid addition, and no effect of isoacid addition was observed on pig performance (P > 0.05). Diet type did not affect ADG (P > 0.05), but pigs fed diets containing DDGS or SBP consumed less feed (P = 0.01) and exhibited greater GF ratios compared to pigs fed the low-fiber CSBM diet (P ≤ 0.05). In conclusion, there was little to no effect of isoacid addition on microbial ecology, fecal VFA concentrations, ATTD of GE or N, or pig performance, but the improvement in ATTD of GE and N in pigs fed diets containing DDGS when IB was added warrants further investigation.

12.
BMC Med Genomics ; 17(1): 165, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898440

RESUMO

BACKGROUND: Respiratory Syncytial Virus (RSV) disease in young children ranges from mild cold symptoms to severe symptoms that require hospitalization and sometimes result in death. Studies have shown a statistical association between RSV subtype or phylogenic lineage and RSV disease severity, although these results have been inconsistent. Associations between variation within RSV gene coding regions or residues and RSV disease severity has been largely unexplored. METHODS: Nasal swabs from children (< 8 months-old) infected with RSV in Rochester, NY between 1977-1998 clinically presenting with either mild or severe disease during their first cold-season were used. Whole-genome RSV sequences were obtained using overlapping PCR and next-generation sequencing. Both whole-genome phylogenetic and non-phylogenetic statistical approaches were performed to associate RSV genotype with disease severity. RESULTS: The RSVB subtype was statistically associated with disease severity. A significant association between phylogenetic clustering of mild/severe traits and disease severity was also found. GA1 clade sequences were associated with severe disease while GB1 was significantly associated with mild disease. Both G and M2-2 gene variation was significantly associated with disease severity. We identified 16 residues in the G gene and 3 in the M2-2 RSV gene associated with disease severity. CONCLUSION: These results suggest that phylogenetic lineage and the genetic variability in G or M2-2 genes of RSV may contribute to disease severity in young children undergoing their first infection.


Assuntos
Variação Genética , Filogenia , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Índice de Gravidade de Doença , Humanos , Infecções por Vírus Respiratório Sincicial/genética , Infecções por Vírus Respiratório Sincicial/virologia , Lactente , Vírus Sincicial Respiratório Humano/genética , Masculino , Genótipo , Feminino , Genoma Viral
13.
Urol Pract ; : 101097UPJ0000000000000629, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38913586

RESUMO

INTRODUCTION: Our goal was to determine if board certification status was associated with improved postoperative outcomes for certain urologic oncology operations. METHODS: We performed a retrospective cohort study of patients aged 65 and over having radical prostatectomy (RP), radical cystectomy (RC), and radical or partial nephrectomy (RPN) by surgeons with New York State licenses from 2015 to 2021 using the Medicare limited dataset. Our primary exposure was surgeon American Board of Urology certification determined by the New York State Physician Profile. All surgeons were in practice for at least 5 years. Our primary outcomes were 90-day mortality, 30-day unplanned readmission, and hospital length of stay (LOS). We used multivariable linear and logistic regression adjusted for surgeon, hospital, and patient characteristics. We performed the analysis in R, and 2-sided P values < .05 were considered statistically significant. RESULTS: We identified 12,601 patients who had a procedure performed. At the time of the procedure, a minority of procedures (1.3%) were performed by nonboard-certified (NBC) urologists. Among the patient cohort, there were 262 and 1419 mortality and readmission events, respectively; median LOS was 2 days (interquartile range 1155). Patients operated on by NBC urologists tended to have lower-volume surgeons who were less likely to be fellowship trained and to have surgery at smaller hospitals. Patients treated by NBC urologists were more likely to have RP, and less likely to have RC and RPN. On multivariate analysis, board certification was protective against readmission for RP (P < .001) and RC (P = .02), longer LOS for RC (P = .001), and mortality for RPN (P = .008). CONCLUSIONS: Urology board certification was associated with fewer readmissions after RP and RC, a shorter LOS after RC, and a lower risk of mortality after RPN. Given low event numbers, these findings require validation with a larger dataset.

14.
Urol Pract ; : 101097UPJ0000000000000640, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38913619

RESUMO

INTRODUCTION: Prolonged indwelling catheter use is a known risk factor for catheter-associated UTIs (CAUTIs). We sought to reduce catheter use by creating and implementing a trial of void (TOV) algorithm to standardize indwelling Foley catheter removal in surgical patients. METHODS: We partnered with the Departments of General Surgery and Nursing to develop an evidence-based TOV algorithm for a step-down unit at a large urban teaching hospital. Our cohort included patients treated with intra-abdominal, thoracic, vascular, urologic, and gynecologic surgeries. The primary outcome was mean cumulative indwelling urethral catheter patient-days. For example, if 2 patients had catheters for 3 and 7 days, respectively, then cumulative catheter days would be 10. We analyzed changes in catheter use 90 days before and after algorithm implementation. RESULTS: The mean number of hospitalized patient-days before and after algorithm introduction did not differ (32.2 vs 32.0, P = .60). After implementation, mean cumulative catheter patient-days decreased (14.8 vs 9.9, P < .01), as did mean daily number of patients with catheters on the unit (3.7 vs 3.1, P = .02). There was 1 CAUTI before and after algorithm implementation, the latter deemed associated with algorithm nonadherence. Catheter use in a surgical floor control group where the algorithm was not implemented did not differ for any outcome over the same time period (P > .05). CONCLUSIONS: A multidisciplinary approach to standardize catheter care with a TOV algorithm is feasible and effective in reducing catheter use. Further research is needed to determine its impact on CAUTI rate.

15.
Integr Comp Biol ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38906840

RESUMO

Understanding how the structure of biological systems impacts their resilience (broadly defined) is a recurring question across multiple levels of biological organization. In ecology, considerable effort has been devoted to understanding how the structure of interactions between species in ecological networks is linked to different broad resilience outcomes, especially local stability. Still, nearly all of that work has focused on interaction structure in presence-absence terms, and has not investigated quantitative structure, i.e., the arrangement of interaction strengths in ecological networks. We investigated how the interplay between binary and quantitative structure impacts stability in mutualistic interaction networks (those in which species interactions are mutually beneficial), using community matrix approaches. We additionally examined the effects of network complexity and within-guild competition for context. In terms of structure, we focused on understanding the stability impacts of nestedness, a structure in which more-specialized species interact with smaller subsets of the same species that more-generalized species interact with. Most mutualistic networks in nature display binary nestedness, which is puzzling because both binary and quantitative nestedness are known to be destabilizing on their own. We found that quantitative network structure has important consequences for local stability. In more-complex networks, binary-nested structures were the most stable configurations, depending on the quantitative structures; but which quantitative structure was stabilizing depended on network complexity and competitive context. As complexity increases, and in the absence of within-guild competition, the most stable configurations have a nested binary structure with a complementary (i.e., anti-nested) quantitative structure. In the presence of within-guild competition, however, the most stable networks are those with a nested binary structure and a nested quantitative structure. In other words, the impact of interaction-overlap on community persistence is dependent on the competitive context. These results help to explain the prevalence of binary nested structures in nature and underscore the need for future empirical work on quantitative structure.

16.
J Urol ; : 101097JU0000000000004071, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38848575
17.
Arterioscler Thromb Vasc Biol ; 44(7): 1674-1682, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38752350

RESUMO

BACKGROUND: A series of incurable cardiovascular disorders arise due to improper formation of elastin during development. Supravalvular aortic stenosis (SVAS), resulting from a haploinsufficiency of ELN, is caused by improper stress sensing by medial vascular smooth muscle cells, leading to progressive luminal occlusion and heart failure. SVAS remains incurable, as current therapies do not address the root issue of defective elastin. METHODS: We use SVAS here as a model of vascular proliferative disease using both human induced pluripotent stem cell-derived vascular smooth muscle cells and developmental Eln+/- mouse models to establish de novo elastin assembly as a new therapeutic intervention. RESULTS: We demonstrate mitigation of vascular proliferative abnormalities following de novo extracellular elastin assembly through the addition of the polyphenol epigallocatechin gallate to SVAS human induced pluripotent stem cell-derived vascular smooth muscle cells and in utero to Eln+/- mice. CONCLUSIONS: We demonstrate de novo elastin deposition normalizes SVAS human induced pluripotent stem cell-derived vascular smooth muscle cell hyperproliferation and rescues hypertension and aortic mechanics in Eln+/- mice, providing critical preclinical findings for the future application of epigallocatechin gallate treatment in humans.


Assuntos
Estenose Aórtica Supravalvular , Catequina , Proliferação de Células , Modelos Animais de Doenças , Elastina , Células-Tronco Pluripotentes Induzidas , Músculo Liso Vascular , Miócitos de Músculo Liso , Elastina/metabolismo , Animais , Humanos , Catequina/análogos & derivados , Catequina/farmacologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Estenose Aórtica Supravalvular/metabolismo , Estenose Aórtica Supravalvular/genética , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Músculo Liso Vascular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Camundongos , Células Cultivadas , Camundongos Endogâmicos C57BL , Feminino , Masculino , Camundongos Knockout
18.
Headache ; 64(6): 663-673, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38700250

RESUMO

OBJECTIVE: To determine the tolerability and safety of concurrent peripheral nerve blocks and onabotulinumtoxinA treatment during a single outpatient clinic procedure visit. BACKGROUND: Procedural interventions are available for the treatment of headache disorders. OnabotulinumtoxinA and peripheral nerve blocks are used as alternatives or in addition to oral therapies to reduce the frequency and intensity of migraine attacks. There is currently a lack of safety data focusing on the sequential administration of local anesthetic via peripheral nerve blocks and onabotulinumtoxinA during a single clinical encounter for the treatment of headache. The primary aim of the study was to determine the safety and tolerability of concurrent peripheral nerve blockade and onabotulinumtoxinA injections during a single outpatient clinic procedure visit. We hypothesized that the dual intervention would be safe and well tolerated by patients with chronic migraine and other headache disorders. METHODS: A retrospective chart review was performed using clinical data from patients seen by multiple providers over a 16-month timeframe at one outpatient headache clinic. Patients were identified by procedure codes and those receiving peripheral nerve block(s) and onabotulinumtoxinA injections during a single encounter within the study period were eligible for inclusion. Inclusion criteria were (1) patients 18 years and older who were (2) receiving both peripheral nerve blocks and onabotulinumtoxinA injections for the treatment of chronic migraine. Patients were excluded if they were under age 18, received their procedure outside of the clinic (emergency room, inpatient ward), or were receiving sphenopalatine ganglion blocks. Age- and sex-matched patients who received one procedure, either peripheral nerve blocks or onabotulinumtoxinA, were used for control. The primary outcome of this safety study was the number of adverse events that occurred in the dual intervention group compared to the single intervention control arms. Information regarding adverse events was gathered via retrospective chart review. If an adverse event was recorded, it was then graded by the reviewer utilizing the Common Terminology Criteria for Adverse Events ranging from Grade 1 Mild Event to Grade 5 Death. Additionally, it was noted whether the adverse event led to treatment discontinuation. RESULTS: In total, 375 patients were considered eligible for inclusion in the study. After age and sex matching of controls, 131 patients receiving dual intervention were able to be compared to 131 patients receiving onabotulinumtoxinA alone and 104 patients receiving dual intervention were able to be compared to 104 patients receiving peripheral nerve block(s) alone. The primary endpoint analysis showed no significant difference in total adverse events between dual intervention compared to nerve blocks alone or onabotulinumtoxinA alone. The number of adverse events that led to treatment discontinuation approached but did not reach statistical significance for those receiving dual intervention versus onabotulinumtoxinA alone in the number of adverse events that led to treatment termination (4.6%, 6/131 vs. 0.8%, 1/131, p = 0.065); however, the number of patients who discontinued therapy was not significantly different between those groups (2.3%, 3/131 vs. 0.8%, 1/131; p = 0.314; odds ratio 0.3 [0-3.2]; p = 0.338). CONCLUSIONS: In this retrospective chart review, there was no significant difference in adverse events or therapy discontinuation between patients receiving sequential peripheral nerve block(s) and onabotulinumtoxinA injections versus those receiving either peripheral nerve block(s) or onabotulinumtoxinA injections alone. As a result, we concluded that the combination procedure is likely safe and well tolerated in routine clinical practice.


Assuntos
Toxinas Botulínicas Tipo A , Transtornos de Enxaqueca , Bloqueio Nervoso , Humanos , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/efeitos adversos , Toxinas Botulínicas Tipo A/farmacologia , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Bloqueio Nervoso/métodos , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos da Cefaleia/tratamento farmacológico , Fármacos Neuromusculares/administração & dosagem , Fármacos Neuromusculares/efeitos adversos , Fármacos Neuromusculares/farmacologia , Idoso , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia
19.
BMJ Neurol Open ; 6(1): e000593, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736584

RESUMO

Background: Educational attainment is a critical social determinant of health that impacts the risk and severity of incident ischaemic stroke, but less is known of its impact on intracerebral haemorrhage (ICH). The objective of this study is to determine whether educational attainment is associated with ICH severity and short-term prognosis. Methods: Subjects were enrolled in a prospectively ascertained cohort with primary ICH from 1994 to 2020 at Massachusetts General Hospital. Educational attainment, medical history of ICH risk factors, ICH volume and ICH score were obtained on admission. The primary outcomes were ICH volume and the ICH score. Results: Of 2539 eligible patients eligible, the median age of the sample was 74 (IQR 64-82) and 2159 (85%) had high school-only education. 1655 (65%) presented with an ICH volume less than or equal to 30 mL and 1744 (69%) presented with an ICH score less than 3. In multivariable logistic regression analyses controlling for age, income, employment history and prestroke diagnoses of hypertension and coronary artery disease, patients with high school-only education were more likely to have an ICH volume greater than 30 mL compared with college diplomates (OR 1.58, 95% CI 1.24 to 2.08) and more likely to have an ICH score of 3 or greater compared with college diplomates (OR 2.37, 95% CI 1.77 to 3.19). Discussion: Prestroke educational attainment is independently associated with ICH severity and short-term prognosis, with lower educational attainment associated with larger ICH volumes and higher ICH scores. Future studies should examine how educational attainment impacts exposure to traditional clinical risk factors.

20.
World J Urol ; 42(1): 315, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734774

RESUMO

INTRODUCTION: The combination of sequential intravesical gemcitabine and docetaxel (Gem/Doce) chemotherapy has been considered a feasible option for BCG (Bacillus Calmette-Guérin) treatment in non-muscle invasive bladder cancer (NMIBC), gaining popularity during BCG shortage period. We seek to determine the efficacy of the treatment by comparing Gem/Doce induction alone vs induction with maintenance, and to evaluate the treatment outcomes of two different dosage protocols. METHODS: A bi-center retrospective analysis of consecutive patients treated with Gem/Doce for NMIBC between 2018 and 2023 was performed. Baseline characteristics, risk group stratification (AUA 2020 guidelines), pathological, and surveillance reports were collected. Kaplan-Meier survival analysis was performed to detect Recurrence-free survival (RFS). RESULTS: Overall, 83 patients (68 males, 15 females) with a median age of 73 (IQR 66-79), and a median follow-up time of 18 months (IQR 9-25), were included. Forty-one had an intermediate-risk disease (49%) and 42 had a high-risk disease (51%). Thirty-seven patients (45%) had a recurrence; 19 (23%) had a high-grade recurrence. RFS of Gem/Doce induction-only vs induction + maintenance was at 6 months 88% vs 100%, at 12 months 71% vs 97%, at 18 months 57% vs 91%, and at 24 months 31% vs 87%, respectively (log-rank, p < 0.0001). Patients who received 2 g Gemcitabine with Docetaxel had better RFS for all-grade recurrences (log-rank, p = 0.017). However, no difference was found for high-grade recurrences. CONCLUSION: Gem/Doce induction with maintenance resulted in significantly better RFS than induction-only. Combining 2 g gemcitabine with docetaxel resulted in better RFS for all-grade but not for high-grade recurrences. Further prospective trials are necessary to validate our results.


Assuntos
Desoxicitidina , Docetaxel , Gencitabina , Invasividade Neoplásica , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Docetaxel/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Masculino , Feminino , Idoso , Estudos Retrospectivos , Administração Intravesical , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia de Manutenção/métodos , Quimioterapia de Indução/métodos , Relação Dose-Resposta a Droga , Resultado do Tratamento , Medição de Risco , Neoplasias não Músculo Invasivas da Bexiga
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