Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 98
Filtrar
1.
Life Sci ; 303: 120601, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35561749

RESUMO

The gut microbiome influences cognition and behavior in mammals, yet its metabolic impact on the brain is only starting to be defined. Using metabolite profiling of antibiotics-treated mice, we reveal the microbiome as a key input controlling circadian metabolic cycles in the brain. Intra and inter-region analyses characterise the influence of the microbiome on the suprachiasmatic nucleus, containing the central clockwork, as well as the hippocampus and cortex, regions involved in learning and behavior.


Assuntos
Antibacterianos , Microbioma Gastrointestinal , Animais , Antibacterianos/farmacologia , Encéfalo/metabolismo , Mamíferos , Camundongos , Núcleo Supraquiasmático
2.
J Knee Surg ; 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35605970

RESUMO

Osteoarthritis (OA) of the knee is thought to lead to a loss of lumbar lordosis (LL) as a compensation for knee flexion contracture. Changes in sagittal alignment are not limited to the lumbar spine and involve a complex interplay of alignment of the hip, pelvis, and spine. While spine-hip interactions have been previously explored, the influence of knee OA sagittal alignment parameters on spinopelvic alignment and global sagittal balance remains unexplored. Standing radiological examination using EOS biplanar radiography was examined in 108 patients with knee OA. Whole-body sagittal alignment parameters (thoracic kyphosis, LL, pelvic incidence, pelvic tilt [PT], femoropelvic angle [FPA], femoral tilt angle [FTA], tibial tilt angle, and knee flexion angle [KFA]) and global balance parameters (sagittal vertical axis [SVA] and odontoid hip axis [OD-HA] angle) were measured three dimensionally (3D). The correlation coefficients among all parameters were assessed. A multiple stepwise linear regression model was built to investigate the direct association between SVA or OD-HA angle (dependent variables) and sagittal alignment parameters and demographic data (independent variables). Significant correlations between KFA, FPA, FTA, SVA, and OD-HA angle were found. FTA was correlated with LL and FPA. The FTA was the most influential predictor of both global sagittal balance parameters (p < 0.001). Knee OA leads to changes in global sagittal balance with effects at the hip, knee, pelvis, and spine. FTA (forward flexion of the femur vs. the vertical plane) is the largest driver of global sagittal plane balance in patients with knee OA.

3.
Methods Mol Biol ; 2485: 175-190, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35618906

RESUMO

Extensive progress has been made in developing engineered models for elucidating human cardiac disease. Cardiac fibrosis is often associated with all forms of cardiac disease and has a direct deleterious effect on cardiac function. As currently there is no effective therapeutic strategy specifically designed to target fibrosis, in vitro diagnostic platforms for drug testing have generated significant interest. In this context, we have developed an innovative approach to generate human cardiac fibrotic tissues on Biowire II platform and established a compound screening system. The disease model is constructed to recapitulate contractile, biomechanical, and electrophysiological complexities of fibrotic myocardium. Additionally, an integrated model with fibrotic and healthy cardiac tissues coupled together can be created to mimic focal fibrosis. The methods for constructing the Biowire fibrotic model will be described here.


Assuntos
Cardiopatias , Miócitos Cardíacos , Fibrose , Humanos , Miocárdio/patologia , Miócitos Cardíacos/patologia
4.
Semin Ophthalmol ; : 1-7, 2022 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-35403560

RESUMO

PURPOSE: To perform a retrospective characterization of one-star reviews of ophthalmologists on Yelp.com and to increase understanding of patient complaints on Yelp.com. METHODS: A search was performed for reviews on Yelp.com using the keyword "ophthalmologist" for the top 8 most population-dense metropolitan areas in the United States. One-star reviews were collected and classified as procedural or nonprocedural. Complaints were also categorized as clinical, nonclinical, or both. Clinical complaints cited issues such as complications, reoperations, uncontrolled pain, misdiagnosis, unclear treatment plan, etc. Nonclinical complaints included comments such as physician bedside manner, other staff interpersonal manner, wait time, brevity of appointment time, etc. RESULTS: 5,532 total reviews were assessed, of which 477 (9%) one-star reviews were included in the study for analysis. These reviews amounted to 1,120 distinct complaints. 287 (26%) were clinical in nature and 833 (74%) were nonclinical. Technical incompetence or error (50: 4%), unsatisfactory results (46: 4%), and complications (43: 4%) represented the most common clinical complaints while office staff interpersonal manner (182: 16%), wait time (174: 16%), and physician interpersonal manner (141: 13%) were the most common nonclinical complaints. Refractive surgery was the most frequently mentioned subspecialty (89: 8%). Patients undergoing an ophthalmic procedure (surgery, injection, etc.) wrote 64 reviews that resulted in 193 (17%) complaints. Nonprocedural patients wrote 413 reviews that resulted in 927 (83%) complaints. Compared with procedural reviews, nonprocedural reviews were less likely to include a clinical complaint (rate ratio, 0.3: P < .001). DISCUSSION: The majority of one-star reviews of ophthalmologists included in this study were nonclinical. Complaints referencing a procedural episode were more likely to include a clinical component in the review. In the era of intense medical consumerism and increased physician and health care institution competition for patient acquisition and retention, the characterization of excessively negative reviews allows identification of potential areas of concern for patients that use online review sites such as Yelp.com.

5.
Ultramicroscopy ; 236: 113513, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35290793

RESUMO

Development in lattice strain mapping using four-dimensional scanning transmission electron microscopy (4D-STEM) method now offers improved precision and feasibility. However, automatic and accurate diffraction analysis is still challenging due to noise and the complexity of intensity in diffraction patterns. In this work, we demonstrate an approach, employing the blob detection on cross-correlated diffraction patterns followed by a lattice fitting algorithm, to automate the processing of four-dimensional data, including identifying and locating disks, and extracting local lattice parameters without prior knowledge about the material. The approach is both tested using simulated diffraction patterns and applied on experimental data acquired from a Pd@Pt core-shell nanoparticle. Our method shows robustness against various sample thicknesses and high noise, capability to handle complex patterns, and picometer-scale accuracy in strain measurement, making it a promising tool for high-throughput 4D-STEM data processing.

6.
Eur J Hosp Pharm ; 2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35177534

RESUMO

PURPOSE: Voluntary event reporting systems continue to be the most common method used to identify adverse events in most US hospitals; however, this method fails to capture more than 90% of adverse drug events (ADEs). The purpose of this study is to examine which medication-related triggers have the highest positive predictive values (PPV) for detecting ADEs at a large academic medical centre. METHODS: A 1-year, single-centre, retrospective quality improvement study was conducted to assess the PPV of four medication-related triggers: flumazenil, naloxone, glucose <70 mg/dL or dextrose 50%. Retrospective chart review was conducted on a random sample of eligible patients to establish if an ADE occurred and determine its preventability. Assessed triggers were also compared against the hospital's voluntary event reporting system to determine whether the events were previously reported. RESULTS: A total of 161 triggers were reviewed. PPV values for detection of ADEs were 0.55, 0.58, 0.76 and 0.68 for flumazenil, naloxone, glucose <70 mg/dL and dextrose 50%, respectively. PPV values for detection of preventable ADEs were 0.09, 0.16, 0.32 and 0.34 for flumazenil, naloxone, glucose <70 mg/dL and dextrose 50%, respectively. Of the 107 ADEs identified, three events were reported through the hospital's voluntary event reporting system (2.8%). CONCLUSIONS: Trigger tools successfully detected both preventable and non-preventable ADEs. Events detected using trigger tools are unlikely to be reported through voluntary event reporting systems; therefore, trigger tools can serve as a useful adjunct for adverse event detection.

7.
JAMA Dermatol ; 158(2): 176-183, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34985493

RESUMO

Importance: Acute generalized exanthematous pustulosis (AGEP) is a rare, severe cutaneous adverse reaction associated with systemic complications. Currently available data are largely limited to small retrospective case series. Objective: To describe the clinical characteristics, disease course, and outcomes of a heterogeneous group of patients with AGEP across the US. Design, Setting, and Participants: A retrospective review of a case series of patients was conducted from January 1, 2000, through July 31, 2020. All 340 included cases throughout 10 academic health systems in the US were scored retrospectively using the EuroSCAR scoring system, and patients with a score corresponding to probable or definite AGEP and aged 18 years or older were included. Main Outcomes and Measures: Patient demographic characteristics, clinical course, suspected causative agent, treatment, and short- and long-term outcomes. Results: Most of the 340 included patients were women (214 [62.9%]), White (206 [60.6%]), and non-Hispanic (239 [70.3%]); mean (SD) age was 57.8 (17.4) years. A total of 154 of 310 patients (49.7%) had a temperature greater than or equal to 38.0 °C that lasted for a median of 2 (IQR, 1-4) days. Of 309 patients, 263 (85.1%) developed absolute neutrophilia and 161 patients (52.1%) developed either absolute or relative eosinophilia. Suspected causes of AGEP were medications (291 [85.6%]), intravenous contrast agents (7 [2.1%]), infection (3 [0.9%]), or unknown (39 [11.5%]). In 151 cases in which a single medication was identified, 63 (41.7%) were ß-lactam antimicrobials, 51 (33.8%) were non-ß-lactam antimicrobials, 9 (6.0%) were anticonvulsants, and 5 (3.3%) were calcium channel blockers. The median time from medication initiation to AGEP start date was 3 (IQR, 1-9) days. Twenty-five of 298 patients (8.4%) had an acute elevation of aspartate aminotransferase and alanine aminotransferase levels, with a peak at 6 (IQR, 3-9) days. Twenty-five of 319 patients (7.8%) experienced acute kidney insufficiency, with the median time to peak creatinine level being 4 (IQR, 2-5) days after the AGEP start date. Treatments included topical corticosteroids (277 [81.5%], either alone or in combination), systemic corticosteroids (109 [32.1%]), cyclosporine (10 [2.9%]), or supportive care only (36 [10.6%]). All-cause mortality within 30 days was 3.5% (n = 12), none of which was suspected to be due to AGEP. Conclusions and Relevance: This retrospective case series evaluation of 340 patients, the largest known study cohort to date, suggests that AGEP onset is acute, is usually triggered by recent exposure to an antimicrobial, may be associated with liver or kidney complications in a minority of patients, and that discontinuation of the triggering treatment may lead to improvement or resolution.


Assuntos
Pustulose Exantematosa Aguda Generalizada , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/etiologia , Adolescente , Antibacterianos/efeitos adversos , Feminino , Glucocorticoides , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Pele
8.
JAMA Dermatol ; 158(1): 73-78, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34878491

RESUMO

IMPORTANCE: Generalized pustular psoriasis (GPP) is a chronic, orphan disease with limited epidemiological data. OBJECTIVE: To describe the clinical characteristics, treatments, longitudinal disease course, and disease-specific health care utilization among patients with GPP across the United States. DESIGN, SETTING, AND PARTICIPANTS: A retrospective longitudinal case series involving 95 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for GPP and were treated at 20 US academic dermatology practices between January 1, 2007, and December 31, 2018. MAIN OUTCOMES AND MEASURES: The primary outcome is to describe the patient characteristics, associated medical comorbidities, treatment patterns complications, and GPP-specific health care utilization. RESULTS: Sixty-seven of 95 patients (70.5%) were women (mean age, 50.3 years [SD, 16.1 years]). In the initial encounter, 35 patients (36.8%) were hospitalized and 64 (67.4%) were treated with systemic therapies. In total, more than 20 different systemic therapies were tried. During the follow-up period, 19 patients (35.8%) reported hospitalizations at a median rate of 0.5 hospitalizations per year (IQR, 0.4-1.6). Women had a decreased risk of an emergency department or hospital encounter (odds ratio, 0.19; 95% CI, 0.04-0.83). CONCLUSIONS AND RELEVANCE: Generalized pustular psoriasis is a rare, chronic disease without standard treatment and is associated with continued health care utilization over time.


Assuntos
Psoríase , Dermatopatias Vesiculobolhosas , Doença Aguda , Adulto , Doença Crônica , Feminino , Humanos , Pessoa de Meia-Idade , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Psoríase/epidemiologia , Estudos Retrospectivos , Estados Unidos/epidemiologia
9.
JAMA Dermatol ; 158(1): 68-72, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34878495

RESUMO

IMPORTANCE: Palmoplantar pustulosis (PPP) is a is a chronic, orphan disease with limited epidemiological data. OBJECTIVE: To describe the clinical characteristics, treatments, longitudinal disease course, and health care utilization in adults with PPP across the US. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, longitudinal case series from 20 academic dermatology practices in the US included a consecutive sample of 197 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for PPP between January 1, 2007, and December 31, 2018. Data analysis was performed June 2020 to December 2020. MAIN OUTCOMES AND MEASURES: The primary outcome was to describe the patient characteristics, associated medical comorbidities, treatment patterns, complications, and PPP-specific health care utilization. RESULTS: Of 197 patients, 145 (73.6%) were female, and the mean (SD) age at presentation was 53.0 (12.6) years, with a mean (SD) follow-up time of 22.1 (28.0) months. On initial presentation, 95 (48.2%) patients reported skin pain, and 39 (19.8%) reported difficulty using hands and/or feet. Seventy patients (35.5%) were treated with systemic treatments, and use of more than 20 different systemic therapies was reported. In patients with at least 6 months of follow-up (n = 128), a median (IQR) of 3.7 (4-10) dermatology visits per year were reported; 24 (18.8%) patients had 5 or more visits during the study period. CONCLUSIONS AND RELEVANCE: In this case series, PPP was associated with persistent symptoms, continued health care utilization, and a lack of consensus regarding effective treatments, emphasizing the unmet medical need in this population. Additional research is necessary to understand treatment response in these patients.


Assuntos
Psoríase , Dermatopatias Vesiculobolhosas , Adulto , Doença Crônica , Comorbidade , Feminino , Humanos , Psoríase/diagnóstico , Psoríase/epidemiologia , Psoríase/terapia , Estudos Retrospectivos , Dermatopatias Vesiculobolhosas/epidemiologia , Estados Unidos/epidemiologia
10.
J Shoulder Elbow Surg ; 31(4): 860-867, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34619346

RESUMO

BACKGROUND: There is a paucity of information regarding financial trends in orthopedic upper extremity surgery. If progress is to be made in advancing agreeable reimbursement models, a more comprehensive understanding of these trends is needed. The purpose of this study was to assess national and geographic trends in Medicare reimbursement rates for shoulder and elbow surgical procedures over the past 2 decades. METHODS: The 10 most billed Common Procedural Terminology (CPT) codes for both orthopedic shoulder surgery and elbow/upper arm surgery were determined. Medicare reimbursement data for these CPT codes were compiled between 2000 and 2020 and adjusted for inflation. The percentage change for each procedure and the average change in reimbursement each year were analyzed. Data from 2000, 2010, and 2020 were organized by state. The total percent change in physician fee and the percent change per year were tabulated for each CPT code using inflation-adjusted data and averaged by state. RESULTS: From 2000 to 2020, when corrected for inflation, shoulder and elbow procedures decreased on average by 29.3% and 24.5%, respectively. Shoulder procedures experienced a greater numerical yet statistically insignificant decline in mean reimbursement percent decrease (P = .16), average percent decrease per year (P = .11), a more negative compound annual growth rate (P = .14), and a greater R-squared value as compared with elbow and upper arm procedures. For shoulder procedures, the average percent difference in inflation-adjusted Medicare reimbursement rates from 2000 to 2020 varied from -22.6% in Alaska to -34.1% in Michigan; division data varied from -27.8% in the Mountain Division to -31.2% in the East North Central Division; and region data varied from -28.3% in the West to -30.5% in the Northeast. For elbow and upper arm procedures, the average percent difference in inflation-adjusted Medicare reimbursement rates from 2000 to 2020 varied from -17.6% in Alaska to -29.8% in Michigan; division data varied from -23.0% in the Mountain Division to -26.7% in the East North Central Division; and region data varied from -23.5% in the West to -25.7% in the Northeast. DISCUSSION: Inflation-adjusted Medicare reimbursement in upper extremity surgery has decreased markedly between 2000 and 2020. The degree of decrease varies geographically. If access to quality and sustainable surgical orthopedic care is to persist in the United States, increased awareness of these trends is important. The trends identified in this study can serve to customize regional health care policymaking.


Assuntos
Procedimentos Ortopédicos , Ortopedia , Idoso , Humanos , Reembolso de Seguro de Saúde , Medicare , Ombro , Estados Unidos
11.
J Trauma Acute Care Surg ; 92(1): 93-97, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34561398

RESUMO

BACKGROUND: Trauma is a major risk factor for the development of a venous thromboembolism (VTE). After observing higher than expected VTE rates within our center's Trauma Quality Improvement Program data, we instituted a change in our VTE prophylaxis protocol, moving to enoxaparin dosing titrated by anti-Xa levels. We hypothesized that this intervention would lower our symptomatic VTE rates. METHODS: Adult trauma patients at a single institution meeting National Trauma Data Standard criteria from April 2015 to September 2019 were examined with regards to VTE chemoprophylaxis regimen and VTE incidence. Two groups of patients were identified based on VTE protocol-those who received enoxaparin 30 mg twice daily without routine anti-Xa levels ("pre") versus those who received enoxaparin 40 mg twice daily with dose titrated by serial anti-Xa levels ("post"). Univariate and multivariate analyses were performed to define statistically significant differences in VTE incidence between the two cohorts. RESULTS: There were 1698 patients within the "pre" group and 1406 patients within the "post" group. The two groups were essentially the same in terms of demographics and risk factors for bleeding or thrombosis. There was a statistically significant reduction in VTE rate (p = 0.01) and deep vein thrombosis rate (p = 0.01) but no significant reduction in pulmonary embolism rate (p = 0.21) after implementation of the anti-Xa titration protocol. Risk-adjusted Trauma Quality Improvement Program data showed an improvement in rate of symptomatic pulmonary embolism from fifth decile to first decile. CONCLUSION: A protocol titrating prophylactic enoxaparin dose based on anti-Xa levels reduced VTE rates. Implementation of this type of protocol requires diligence from the physician and pharmacist team. Further research will investigate the impact of protocol compliance and time to appropriate anti-Xa level on incidence of VTE. LEVEL OF EVIDENCE: Therapeutic/care management, Level IV.


Assuntos
Cálculos da Dosagem de Medicamento , Enoxaparina , Inibidores do Fator Xa , Hemorragia , Tromboembolia Venosa , Ferimentos e Lesões , Testes de Coagulação Sanguínea/métodos , Quimioprevenção/efeitos adversos , Quimioprevenção/métodos , Quimioprevenção/normas , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Fator Xa/análise , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/sangue , Feminino , Hemorragia/sangue , Hemorragia/etiologia , Hemorragia/prevenção & controle , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Embolia Pulmonar/sangue , Embolia Pulmonar/etiologia , Embolia Pulmonar/prevenção & controle , Melhoria de Qualidade/organização & administração , Sistema de Registros/estatística & dados numéricos , Risco Ajustado/métodos , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Ferimentos e Lesões/complicações , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/terapia
12.
Mil Med ; 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34939645

RESUMO

INTRODUCTION: The coronavirus disease (COVID-19) pandemic presented unique challenges for surveillance of the military population, which include active component service members and their family members. Through integrating multiple Department of Defense surveillance systems, the Army Public Health Center can provide near real-time case counts to Army leadership on a daily basis. MATERIALS AND METHODS: The incidence of COVID-19 was tracked by incorporating data from the Disease Reporting System Internet, laboratory test results, Commanders' Critical Incidence Reports, reports from the Centers for Disease Control and Prevention military liaison, and media reports. Cases were validated via a medical record review for all Army beneficiaries. Descriptive analyses were performed using Microsoft Excel and SAS 9.4 to measure demographic frequencies. RESULTS: In the first year of the pandemic from February 1, 2020 to February 28, 2021, a total of 96,315 COVID-19 cases were reported to the Disease Reporting System internet, the Army's passive surveillance system, of which 95,429 (99%) were confirmed and 886 (1%) were probable. A total of 76 outbreak reports were submitted from 14 Army installations. The proportion of Army beneficiaries with severe illness was low: 2,271 (2.4%) individuals required hospitalization and 269 (0.3%) died. Installations in Texas reported the highest proportion of confirmed-not hospitalized cases (n = 19,246, 20.7%), confirmed-hospitalized cases (n = 1,037, 45.7%), and deaths (n = 137, 50.9%) as compared to other states with Army installations. CONCLUSIONS: The pandemic has demonstrated the need for a robust public health enterprise with a focus on data collection, validation, and analysis, allowing leaders to make informed decisions that may impact the health of the Army.

13.
Arthrosc Sports Med Rehabil ; 3(5): e1465-e1472, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34746847

RESUMO

PURPOSE: To examine and characterize extremely negative Yelp reviews of orthopedic sports surgeons in the United States. METHODS: A search for reviews was performed using the keywords "Orthopedic Sports Medicine" on Yelp.com for 8 major metropolitan areas. Single-star reviews were isolated for analysis, and individual complaints were then categorized as clinical or nonclinical. The reviews were classified as surgical or nonsurgical. RESULTS: A total of 11,033 reviews were surveyed. Of these, 1,045 (9.5%) were identified as 1-star, and 289 were ultimately included in the study. These reviews encompassed 566 total complaints, 133 (23%) of which were clinical, and 433 (77%) of which were nonclinical in nature. The most common clinical complaints concerned complications (32 complaints; 6%), misdiagnosis (29 complaints; 5%), and uncontrolled pain (21 complaints; 4%). The most common nonclinical complaints concerned physicians' bedside manner (120 complaints; 21%), unprofessional staff (98 complaints; 17%), and finances (78 complaints; 14%). Patients who had undergone surgery wrote 47 reviews that resulted in 114 complaints (20.5% of total complaints), whereas nonsurgical patients were responsible for 242 reviews and a total of 452 complaints (81.3% of total complaints). The difference in the number of complaints by patients after surgery and patients without surgery was statistically significant (P < 0.05) for all categories except for uncontrolled pain, delay in care, bedside manner of midlevel staff, and facilities. CONCLUSION: Our study of extremely negative Yelp reviews found that 77% of negative complaints were nonclinical in nature. The most common clinical complaints were complications, misdiagnoses and uncontrolled pain. Only 16% of 1-star reviews were from surgical patients. CLINICAL RELEVANCE: Patients use online review platforms when choosing surgeons. A comprehensive understanding of factors affecting patient satisfaction and dissatisfaction is needed. The results of our study could be used to guide future quality-improvement measures and to assist surgeons in maintaining favorable online reputations.

14.
Shoulder Elbow ; 13(6): 671-676, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34804216

RESUMO

BACKGROUND: Elbow and forearm motion are thought to affect elbow load transmission, yet little empirical evidence exists to quantify the biomechanics. METHODS: Eight fresh-frozen human cadaver upper extremities were utilized. A 100 N axial force was applied across the elbow joint at elbow flexion angles of (0°, 30°, 60°, and 90°) and forearm rotation angles (0°, 45° supination, and 45° pronation). Pressure mapping sensors were placed in both the radiocapitellar and ulnotrochlear joints. Force distributions and contact areas were measured, and paired t-tests were used for comparison (p < 0.05). RESULTS: The average maximum loading percentage of the radiocapitellar and ulnotrochlear joint pressures were 57.8 ± 4.6% and 42.2 ± 4.6%, respectively. Elbow flexion angle and forearm rotation did not significantly affect the joint loading. There was no significant difference between the contact areas of each joint, although ulnotrochlear and radiocapitellar joints demonstrated an inverse relationship. CONCLUSION: Our study is the only one to date to comprehensively evaluate loading mechanics throughout both functional elbow flexion and forearm rotation across both articulations. The load sharing ratio across the radiocapitellar and ulnotrochlear joints was 58%:42%, agreeing with previously reported ratios with limited parameters. A relationship may be present between increasing radiocapitellar and decreasing ulnotrochlear contact areas as elbow flexion increases.

15.
Int J Equity Health ; 20(1): 230, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34666781

RESUMO

BACKGROUND: Numerous reports have demonstrated the disproportionate impact that COVID-19 has had on vulnerable populations. Our purpose is to describe our health care system's response to this impact. METHODS: We convened a Workgroup with the goal to mitigate the impact of COVID-19 on the most medically vulnerable people in Springfield, Massachusetts, USA, particularly those with significant social needs. We did this through (1) identifying vulnerable patients in high-need geographic areas, (2) developing and implementing a needs assessment/outreach tool tailored to meet cultural, linguistic and religious backgrounds, (3) surveying pharmacies for access to medication delivery, (4) gathering information about sources of food delivery, groceries and/or prepared food, (5) gathering information about means of travel, and (6) assessing need for testing. We then combined these six elements into a patient-oriented branch and a community outreach/engagement branch. CONCLUSIONS: Our highly intentional and methodical approach to patient and community outreach with a strong geographic component has led to fruitful efforts in COVID-19 mitigation. Our patient-level outreach engages our health centers' clinical teams, particularly community health workers, and is providing the direct benefit of material and service resources for our at-risk patients and their families. Our community efforts leveraged existing relationships and created new partnerships that continue to inform us-healthcare entities, healthcare employees, and clinical teams-so that we can grow and learn in order to authentically build trust and engagement.


Assuntos
COVID-19 , Agentes Comunitários de Saúde , Atenção à Saúde , Humanos , SARS-CoV-2 , Análise de Sistemas
16.
Sci Adv ; 7(39): eabi7828, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34550736

RESUMO

The mammalian circadian clock, expressed throughout the brain and body, controls daily metabolic homeostasis. Clock function in peripheral tissues is required, but not sufficient, for this task. Because of the lack of specialized animal models, it is unclear how tissue clocks interact with extrinsic signals to drive molecular oscillations. Here, we isolated the interaction between feeding and the liver clock by reconstituting Bmal1 exclusively in hepatocytes (Liver-RE), in otherwise clock-less mice, and controlling timing of food intake. We found that the cooperative action of BMAL1 and the transcription factor CEBPB regulates daily liver metabolic transcriptional programs. Functionally, the liver clock and feeding rhythm are sufficient to drive temporal carbohydrate homeostasis. By contrast, liver rhythms tied to redox and lipid metabolism required communication with the skeletal muscle clock, demonstrating peripheral clock cross-talk. Our results highlight how the inner workings of the clock system rely on communicating signals to maintain daily metabolism.

17.
PLoS Comput Biol ; 17(8): e1009227, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34351901

RESUMO

For many biological systems, a variety of simulation models exist. A new simulation model is rarely developed from scratch, but rather revises and extends an existing one. A key challenge, however, is to decide which model might be an appropriate starting point for a particular problem and why. To answer this question, we need to identify entities and activities that contributed to the development of a simulation model. Therefore, we exploit the provenance data model, PROV-DM, of the World Wide Web Consortium and, building on previous work, continue developing a PROV ontology for simulation studies. Based on a case study of 19 Wnt/ß-catenin signaling models, we identify crucial entities and activities as well as useful metadata to both capture the provenance information from individual simulation studies and relate these forming a family of models. The approach is implemented in WebProv, a web application for inserting and querying provenance information. Our specialization of PROV-DM contains the entities Research Question, Assumption, Requirement, Qualitative Model, Simulation Model, Simulation Experiment, Simulation Data, and Wet-lab Data as well as activities referring to building, calibrating, validating, and analyzing a simulation model. We show that most Wnt simulation models are connected to other Wnt models by using (parts of) these models. However, the overlap, especially regarding the Wet-lab Data used for calibration or validation of the models is small. Making these aspects of developing a model explicit and queryable is an important step for assessing and reusing simulation models more effectively. Exposing this information helps to integrate a new simulation model within a family of existing ones and may lead to the development of more robust and valid simulation models. We hope that our approach becomes part of a standardization effort and that modelers adopt the benefits of provenance when considering or creating simulation models.


Assuntos
Modelos Biológicos , Via de Sinalização Wnt , Animais , Fenômenos Bioquímicos , Biologia Computacional , Gráficos por Computador , Simulação por Computador , Humanos , Software , Biologia de Sistemas
18.
Sci Rep ; 11(1): 16439, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385559

RESUMO

Inhalation of dry powder synthetic lung surfactant may assist spontaneous breathing by providing noninvasive surfactant therapy for premature infants supported with nasal continuous positive airway pressure. Surfactant was formulated using spray-drying with different phospholipid compositions (70 or 80 total weight% and 7:3 or 4:1 DPPC:POPG ratios), a surfactant protein B peptide analog (KL4, Super Mini-B, or B-YL), and Lactose or Trehalose as excipient. KL4 surfactant underperformed on initial adsorption and surface activity at captive bubble surfactometry. Spray-drying had no effect on the chemical composition of Super Mini-B and B-YL peptides and surfactant with these peptides had excellent surface activity with particle sizes and fine particle fractions that were well within the margins for respiratory particles and similar solid-state properties. Prolonged exposure of the dry powder surfactants with lactose as excipient to 40 °C and 75% humidity negatively affected hysteresis during dynamic cycling in the captive bubble surfactometer. Dry powder synthetic lung surfactants with 70% phospholipids (DPPC and POPG at a 7:3 ratio), 25% trehalose and 3% of SMB or B-YL showed excellent surface activity and good short-term stability, thereby qualifying them for potential clinical use in premature infants.


Assuntos
Aerossóis/química , Pós/química , Surfactantes Pulmonares/química , Surfactantes Pulmonares/uso terapêutico , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Sequência de Aminoácidos , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
19.
J Mol Cell Cardiol ; 160: 97-110, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34216608

RESUMO

Angiotensin II (Ang II) presents a critical mediator in various pathological conditions such as non-genetic cardiomyopathy. Osmotic pump infusion in rodents is a commonly used approach to model cardiomyopathy associated with Ang II. However, profound differences in electrophysiology and pharmacokinetics between rodent and human cardiomyocytes may limit predictability of animal-based experiments. This study investigates the application of an Organ-on-a-chip (OOC) system in modeling Ang II-induced progressive cardiomyopathy. The disease model is constructed to recapitulate myocardial response to Ang II in a temporal manner. The long-term tissue cultivation and non-invasive functional readouts enable monitoring of both acute and chronic cardiac responses to Ang II stimulation. Along with mapping of cytokine secretion and proteomic profiles, this model presents an opportunity to quantitatively measure the dynamic pathological changes that could not be otherwise identified in animals. Further, we present this model as a testbed to evaluate compounds that target Ang II-induced cardiac remodeling. Through assessing the effects of losartan, relaxin, and saracatinib, the drug screening data implicated multifaceted cardioprotective effects of relaxin in restoring contractile function and reducing fibrotic remodeling. Overall, this study provides a controllable platform where cardiac activities can be explicitly observed and tested over the pathological process. The facile and high-content screening can facilitate the evaluation of potential drug candidates in the pre-clinical stage.


Assuntos
Angiotensina II/efeitos adversos , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Animais , Cardiomiopatias/patologia , Cardiotônicos/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Avaliação Pré-Clínica de Medicamentos/métodos , Fibroblastos/metabolismo , Fibrose , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Dispositivos Lab-On-A-Chip , Losartan/farmacologia , Camundongos , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Projetos Piloto , Proteoma , Proteômica/métodos , Proteínas Recombinantes/farmacologia , Relaxina/farmacologia , Remodelação Ventricular/efeitos dos fármacos
20.
Eur Heart J ; 42(32): 3063-3073, 2021 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-34263907

RESUMO

AIMS: The aim of this study was to determine the frequency of heterozygous truncating ALPK3 variants (ALPK3tv) in patients with hypertrophic cardiomyopathy (HCM) and confirm their pathogenicity using burden testing in independent cohorts and family co-segregation studies. METHODS AND RESULTS: In a discovery cohort of 770 index patients with HCM, 12 (1.56%) were heterozygous for ALPK3tv [odds ratio(OR) 16.11, 95% confidence interval (CI) 7.94-30.02, P = 8.05e-11] compared to the Genome Aggregation Database (gnomAD) population. In a validation cohort of 2047 HCM probands, 32 (1.56%) carried heterozygous ALPK3tv (OR 16.17, 95% CI 10.31-24.87, P < 2.2e-16, compared to gnomAD). Combined logarithm of odds score in seven families with ALPK3tv was 2.99. In comparison with a cohort of genotyped patients with HCM (n = 1679) with and without pathogenic sarcomere gene variants (SP+ and SP-), ALPK3tv carriers had a higher prevalence of apical/concentric patterns of hypertrophy (60%, P < 0.001) and of a short PR interval (10%, P = 0.009). Age at diagnosis and maximum left ventricular wall thickness were similar to SP- and left ventricular systolic impairment (6%) and non-sustained ventricular tachycardia (31%) at baseline similar to SP+. After 5.3 ± 5.7 years, 4 (9%) patients with ALPK3tv died of heart failure or had cardiac transplantation (log-rank P = 0.012 vs. SP- and P = 0.425 vs. SP+). Imaging and histopathology showed extensive myocardial fibrosis and myocyte vacuolation. CONCLUSIONS: Heterozygous ALPK3tv are pathogenic and segregate with a characteristic HCM phenotype.


Assuntos
Cardiomiopatia Hipertrófica , Proteínas Musculares/genética , Proteínas Quinases/genética , Cardiomiopatia Hipertrófica/genética , Heterozigoto , Humanos , Mutação , Sarcômeros
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...