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Older Texans living in rural areas may face challenges in accessing resources and services not felt by their urban counterparts, especially related to fall risk reduction. In a state the size of Texas, entities wishing to serve these individuals encounter barriers due to the vast geography that must be covered to reach rural communities. This paper explores a novel partnership between a university and a community organization to work toward rural equity in fall risk reduction education in Texas. We apply the Interactive and Contextual Model of Community-University Collaboration to describe efforts to gain entry into rural communities, develop and sustain the partnership, recognize outcomes, and resolve threats. Through shared decision-making and co-creation, we show how university-community partnerships can be a powerful tool for promoting rural equity and ensuring older, rural Texans have access to fall risk reduction education.
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PURPOSE: The gold standard measure of anaerobic contribution is accumulated oxygen deficit (AOD). The purpose of this study was to investigate the validity of an alternate measure, AOD_alt. AOD_alt is the sum of the phosphocreatine and glycolytic contributions, which are estimated from post-exercise oxygen uptake and blood lactate concentration, respectively. METHODS: In Study One, six women and three men performed 6-min bouts of heavy intensity cycle ergometer exercise, once in normoxia (FIO2 ~ 21%) and twice under hypoxic conditions (FIO2 ~ 15% and ~ 12%). In Study Two, four women and two men performed severe intensity tests to exhaustion, once in normoxia (~ 10 min) and twice in hypoxia (FIO2 ~ 15% and ~ 10%). Physiological responses were measured during exercise and 7 min of recovery. RESULTS: In 6 min of heavy exercise, Study One, the alternate and criterion measures of anaerobic contribution (AOD_alt and AOD) were correlated, in normoxia and in hypoxia. In exhaustive severe exercise, Study Two, AOD_alt and AOD were correlated (r = 0.77) and similar, in normoxia and at FIO2 ~ 15%. However, AOD_alt and AOD values were neither correlated (r = 0.27) nor similar (57 ± 5 mL·kg-1 vs 51 ± 7 mL·kg-1) at FIO2 ~ 10%. CONCLUSION: These results confirm the validity of AOD_alt as a measure of anaerobic capacity in severe intensity exercise, demonstrate its validity in heavy exercise, and assert its validity in conditions of hypoxia (FIO2 ~ 12%).
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OBJECTIVES: To characterize state laws targeting patient brokering and deceptive marketing of substance use disorder (SUD) treatment. BACKGROUND: Patient brokering and deceptive marketing of SUD treatment leads to poor outcomes for individuals with SUD, including relapse- or overdose-related hospitalizations, ED visits, or death. In response, several states within the United States have passed laws targeting unethical practices of SUD treatment in recent years. The context in which these laws were passed has not been previously described. The extent to which states engaged in recovery residence regulation that also pass patient brokering and deceptive marketing laws is unknown. METHODS: We conducted a descriptive study and identified state laws relating to patient brokering and deceptive marketing that were enacted and effective as of December 31, 2022. Using a model state law for addressing unethical SUD treatment practices as a guide, we developed a taxonomy to describe the laws' elements, including covered entities, prohibited activities, and penalties. We used descriptive statistics to characterize variation across current laws. RESULTS: All patient brokering laws explicitly mention referrals to SUD treatment facilities, and most specify that both individuals and facilities are prohibited from paying, receiving, or soliciting referrals in exchange for fees or commissions. All deceptive marketing laws prohibit making false or misleading statements about the nature of services provided. Beyond these common features, there is wide variability in the degree to which states specifically prohibit other patient brokering and deceptive marketing activities (e.g., indirect offerings, lead generation, or kickback schemes involving laboratories). CONCLUSIONS: State policies targeting patient brokering and deceptive marketing may be useful for preventing instances of unethical SUD treatment practices. We constructed a taxonomy to characterize elements of patient brokering and deceptive marketing laws and facilitate future evaluations of their effectiveness.
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BACKGROUND: Proton-pump inhibitor (PPI) use for management of gastroesophageal reflux disease (GERD) consists of a short-duration trial, according to guidelines. Long-term usage is appropriate under certain indications. Literature has increasingly documented an adverse effect profile of PPIs, including kidney disease and bone fragility. OBJECTIVE: To investigate the rate of occurrence of osteopenia, osteoporosis, and chronic kidney disease (CKD) in patients using PPI therapy for longer than the recommended trial period of 8 weeks. METHODS: Retrospective cohort analysis of a single-site primary care clinic. Patients aged 18 to 65 years with PPI prescriptions longer than 8 weeks were included. Information regarding PPI prescriptions, demographics, and medical diagnoses was collected. RESULTS: The search discovered 293 PPI-users and 1908 never-PPI-users. Demographics varied, with a P-value <0.05 in age, body mass index (BMI), and black population (higher in PPI group). The PPI cohort featured higher rates of osteoporosis/osteopenia and CKD (P < 0.001). The odds ratios (ORs) of diagnosis with PPI use was 2.91 (95% CI = [1.692, 4.979]) in osteoporosis/osteopenia. The OR was 1.14 (95% CI = [1.141, 2.229]) in CKD and PPI use but higher with diabetes, elevated BMI, black race, and male gender. CONCLUSIONS AND RELEVANCE: We observed increased occurrence rates of osteoporosis, or osteopenia, and CKD in patients with prolonged PPI use. Demographics varied in age, BMI, and black race proportion. A logistic regression revealed increased likelihood of kidney disease and osteoporosis/osteopenia in association with PPI use. These results add to the evidence regarding long-term PPI use and the development of these conditions, but additional studies are needed.
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Microglia play a critical role in maintaining central nervous system (CNS) homeostasis and display remarkable plasticity in their response to inflammatory stimuli. However, the specific signaling profiles that microglia adopt during such challenges remain incompletely understood. Traditional transcriptomic approaches provide valuable insights, but fail to capture dynamic post-translational changes. In this study, we utilized time-resolved single-cell mass cytometry (CyTOF) to measure distinct signaling pathways activated in microglia upon exposure to bacterial and viral mimetics-lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid (Poly(I:C)), respectively. Furthermore, we evaluated the immunomodulatory role of astrocytes on microglial signaling in mixed cultures. Microglia or mixed cultures derived from neonatal mice were treated with LPS or Poly(I:C) for 48 hrs. Cultures were stained with a panel of 33 metal-conjugated antibodies targeting signaling and identity markers. High-dimensional clustering analysis was used to identify emergent signaling modules. We found that LPS treatment led to more robust early activation of pp38, pERK, pRSK, and pCREB compared to Poly(I:C). Despite these differences, both LPS and Poly(I:C) upregulated the classical activation markers CD40 and CD86 at later time-points. Strikingly, the presence of astrocytes significantly blunted microglial responses to both stimuli, particularly dampening CD40 upregulation. Our studies demonstrate that single-cell mass cytometry effectively captures the dynamic signaling landscape of microglia under pro-inflammatory conditions. This approach may pave the way for targeted therapeutic investigations of various neuroinflammatory disorders. Moreover, our findings underscore the necessity of considering cellular context, such as astrocyte presence, in interpreting microglial behavior during inflammation.
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Rhomboid proteases are universally conserved and facilitate the proteolysis of peptide bonds within or adjacent to cell membranes. While eukaryotic rhomboid proteases have been demonstrated to harbor unique cellular roles, prokaryotic members have been far less characterized. For the first time, we demonstrate that Vibrio cholerae expresses two active rhomboid proteases that cleave a shared substrate at distinct sites, resulting in differential localization of the processed protein. The rhomboid protease rhombosortase (RssP) was previously found to process a novel C-terminal domain called GlyGly-CTERM, as demonstrated by its effect on the extracellular serine protease VesB during its transport through the V. cholerae cell envelope. Here, we characterize the substrate specificity of RssP and GlpG, the universally conserved bacterial rhomboid proteases. We show that RssP has distinct cleavage specificity from GlpG, and specific residues within the GlyGly-CTERM of VesB target it to RssP over GlpG, allowing for efficient proteolysis. RssP cleaves VesB within its transmembrane domain, whereas GlpG cleaves outside the membrane in a disordered loop that precedes the GlyGly-CTERM. Cleavage of VesB by RssP initially targets VesB to the bacterial cell surface and, subsequently, to outer membrane vesicles, while GlpG cleavage results in secreted, fully soluble VesB. Collectively, this work builds on the molecular understanding of rhomboid proteolysis and provides the basis for additional rhomboid substrate recognition while also demonstrating a unique role of RssP in the maturation of proteins containing a GlyGly-CTERM. IMPORTANCE: Despite a great deal of insight into the eukaryotic homologs, bacterial rhomboid proteases have been relatively understudied. Our research aims to understand the function of two rhomboid proteases in Vibrio cholerae. This work is significant because it will help us better understand the catalytic mechanism of rhomboid proteases as a whole and assign a specific role to a unique subfamily whose function is to process a subset of effector molecules secreted by V. cholerae and other pathogenic bacteria.
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Proteínas de Bactérias , Proteólise , Vibrio cholerae , Vibrio cholerae/enzimologia , Vibrio cholerae/genética , Especificidade por Substrato , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Endopeptidases/metabolismo , Endopeptidases/genética , Endopeptidases/química , Processamento de Proteína Pós-Traducional , Serina Proteases/metabolismo , Serina Proteases/genética , Serina Proteases/químicaRESUMO
BACKGROUND: As more integrated cardiothoracic (CT) surgical residency programs are developed, there is increased interest in factors influencing specialty selection during undergraduate medical education. This study aimed to nationally assess interests and perceptions of CT surgery from medical students pursuing surgery and factors influencing such interests. METHODS: Active members of the American College of Osteopathic Surgeons - Medical Student Section were invited to complete an original survey. Means and 95% confidence intervals were calculated and graphed for questions using Likert scale responses. The comparison of mean responses for students in preclinical versus clinical years was assessed by a Kruskal-Wallis non-parametric ANOVA. Differences between response proportions were assessed via Bonferroni Comparison of Column Proportions. RESULTS: There were 306 surveys completed. Interest in CT surgery was indicated by 10.24% of respondents with preclinical students comprising 84.3% of those responses. Most students interested in CT surgery experienced certain factors including clinical exposure (78.4%), shadowing (81.8%), volunteering (57.1%), and significant personal/life events (86.2%) before medical school. Preclinical students noted exposure to CT surgery during preclinical years would further increase their interest when compared to clinical students (µ=4.12 versus µ=3.51, P<0.000). Importantly, clinical students feel significantly less supported by their school to pursue CT surgery compared to preclinical students (µ=2.45 versus µ=3.40, P<0.000). CONCLUSIONS: All factors establishing interest in CT surgery occurred before students entered medical school and during preclinical years. While there are negative perceptions associated with CT surgery, these may be ameliorated with increased support and resources for CT surgery during the preclinical years.
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This study aimed to measure personal exposure to sulfuric acid in the electroplating industry to establish a predictive model and test its validation. We collected indoor air parameters and related information from four electroplating plants. Silica gel sorbents were used to collect air samples using high-performance ion chromatography. We collected air samples from three plants (i.e., Plant B, Plant C, and Plant D) and applied multiple linear regressions to build a predictive model. Eight samples collected from the fourth plant (i.e., Plant A) were used to validate the model. A total of 41 samples were collected with a mean of 25.0 ± 9.8 µg/m3 (range 12.1-51.7 µg/m3) in this study, including Plant A (8 samples, 17.5 ± 2.8 µg/m3, 13.0-22.0 µg/m3), Plant B (11 samples, 36.5 ± 9.7 µg/m3, 23.1-51.7 µg/m3), Plant C (11 samples, 16.4 ± 1.7 µg/m3, 12.1-17.8 µg/m3), and Plant D (11 samples, 27.4 ± 1.7 µg/m3, 24.1-29.9 µg/m3). Plant B was significantly higher in sulfuric acid than the other plants. Workers from the electroplating process plants were exposed to sulfuric acid at 29.0 ± 11.5 µg/m3. The predictive model for personal exposure to sulfuric acid fit the data well (r2 = 0.853; adjusted r2 = 0.837) and had an accuracy of 5.52 µg/m3 (bias ± precision; 4.98 ± 2.38 µg/m3), validated by the personal sampling of the fourth plant. This study observed that sulfuric acid exposure was lower than the permissible exposure level of 1000 µg/m3 in Taiwan and the United States, and only two samples were lower than the European Union standard of 50 µg/m3. The developed model can be applied in epidemiological studies to predict personal exposure to sulfuric acid in plants using electroplating.
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Background: This study investigated the impact of COVID-19 on patients with sickle cell crisis (SCC) using National Inpatient Sample (NIS) data for the year 2020. Methods: A retrospective cohort analysis was conducted utilizing International Classification of Diseases (ICD-10) codes to identify adults who were admitted with a principal diagnosis of sickle cell crisis. The primary outcomes examined were inpatient mortality, while the secondary outcomes assessed included morbidity, hospital length of stay, and resource utilization. Analyses were conducted with STATA. Multivariate logistic and linear regression analyses were used to adjust for confounding variables. Results: Of 66,415 adult patients with a primary SCC diagnosis, 875 were identified with a secondary diagnosis of COVID-19 infection. Unadjusted mortality rate was higher for SCC patients with COVID-19 (2.28%) compared to those without (0.33%), with an adjusted odds ratio (aOR) of 8.49 (p = 0.001). They also showed increased odds of developing acute respiratory failure (aOR = 2.37, p = 0.003) and acute kidney injury requiring dialysis (aOR = 8.66, p = 0.034). Additionally, these patients had longer hospital stays by an adjusted mean of 3.30 days (p < 0.001) and incurred higher hospitalization charges by an adjusted mean of USD 35,578 (p = 0.005). Conclusions: The SCC patients with COVID-19 presented higher mortality rates, increased morbidity indicators, longer hospital stays, and substantial economic burdens.
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BACKGROUND: Medicare beneficiaries are increasingly enrolling in Medicare Advantage (MA), which employs a wide range of practices around restriction of the networks of providers that beneficiaries visit. Though Medicare beneficiaries highly value provider choice, it is unknown whether the MA contract quality metrics which beneficiaries use to inform their contract selection capture the restrictiveness of contracts' provider networks. OBJECTIVE: We evaluated whether there are meaningful associations between provider network restrictiveness (across primary care, psychiatry, and endocrinology providers) and contracts' overall star quality rating, as well as between network restrictiveness and contracts' performance on access to care measures from the Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey. PARTICIPANTS: Medicare Advantage contracts with health maintenance organization (HMO), local preferred provider organization (PPO), and point of service (POS) plans with available data. DESIGN: A cross-sectional analysis using multivariable linear regressions to assess the relationship between provider network restrictiveness and contract quality scores in 2013 through 2017. MEASURES: Statistical significance in the relationship between network restrictiveness and contract performance on quality measures. RESULTS: Across all study years, we included 562 unique contracts and 2801 contract-years. We find no evidence of consistent relationships between MA physician network restrictiveness and contract star rating. For primary care, psychiatry, and endocrinology, respectively, a 10 percentage point increase in restrictiveness was associated with a 0.02 (95% confidence interval [CI] -0.01 to 0.04), 0.0008 (95% CI, -0.01 to 0.02), and -0.01 (95% CI, -0.01 to 0.001) difference in star rating (p-value > 0.05 for all). Similarly, we find no evidence of consistent relationships between network restrictiveness and access to care measures. CONCLUSIONS: Our findings suggest that existing MA contract quality measures are not useful for indicating differences in network restrictiveness. Given the importance of provider choice to beneficiaries, more specific metrics may be needed to facilitate informed decisions about MA coverage.
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Minimal change disease (MCD), typically linked with pediatric nephrotic syndrome, presents challenges in early identification and diagnosis in adult populations. This case report emphasizes the importance of tailored diagnostic and treatment approaches for adults with MCD. Our patient presented with fatigue, shortness of breath, and confusion, along with other symptoms leading to a renal biopsy which confirmed MCD. This highlights the diagnostic significance of kidney biopsy in adults. While steroids remain the standard treatment, challenges such as resistance and side effects lead to the consideration of alternatives like tacrolimus. There are nuanced differences between adult and pediatric MCD presentations, for which our study calls for increased awareness among physicians. Steroids are considered a first-line treatment for MCD, but prolonged use of steroids has significantly increased risk and alternative therapies should be considered. This study presents an example of MCD in adult populations, urging ongoing research for enhanced understanding and tailored management strategies. It emphasizes the pivotal role of physician awareness, alternative treatments, and continued investigation to improve outcomes for adults with MCD.
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PURPOSE OF REVIEW: Spinal cord injury (SCI) is a major cause of morbidity and mortality, posing a significant financial burden on patients and the healthcare system. While little can be done to reverse the primary mechanical insult, minimizing secondary injury due to ischemia and inflammation and avoiding complications that adversely affect neurologic outcome represent major goals of management. This article reviews important considerations in the acute critical care management of SCI to improve outcomes. RECENT FINDINGS: Neuroprotective agents, such as riluzole, may allow for improved neurologic recovery but require further investigation at this time. Various forms of neuromodulation, such as transcranial magnetic stimulation, are currently under investigation. Early decompression and stabilization of SCI is recommended within 24 h of injury when indicated. Spinal cord perfusion may be optimized with a mean arterial pressure goal from a lower limit of 75-80 to an upper limit of 90-95 mmHg for 3-7 days after injury. The use of corticosteroids remains controversial; however, initiation of a 24-h infusion of methylprednisolone 5.4 mg/kg/hour within 8 h of injury has been found to improve motor scores. Attentive pulmonary and urologic care along with early mobilization can reduce in-hospital complications.
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Cuidados Críticos , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/terapia , Cuidados Críticos/métodos , Fármacos Neuroprotetores/uso terapêuticoRESUMO
Uterine leiomyomas (ULs) are common benign tumors seen in a large percent of women that can be classified based on their location within the uterus. They can cause a number of pelvic complications and can be managed medically, but more often surgically. Uterine pyomyomas often occur postpartum, possibly from infarction, and can lead to degeneration and sepsis. Our patient presents with a two-month development of a potential pyomyoma, found initially on computed tomography (CT). Office exam reveals a protruding mass from the cervical os, and removal was attempted but ultimately postponed for general anesthesia exam due to pain. The leiomyoma was removed and shown to be necrosing. Pyomyomas are often insidious and can often mimic other concerning pathologies. Modern imaging can show lesions within the pelvis but struggle to determine between fluid collection and possible infarcted masses. The importance of quality care measures in cases like this deserve to be emphasized to prevent serious complications.
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Medicare enrollment is complex, particularly for low-income individuals who are dually eligible for Medicare and Medicaid, and the wrong plan choice can adversely impact beneficiaries' out-of-pocket costs and access to providers and medications. The State Health Insurance Assistance Program (SHIP) is a federal program that provides counseling on Medicare coverage, but the degree to which SHIP services are accessible to low-income beneficiaries is unknown. We interviewed SHIP counselors and coordinators to characterize factors affecting access to and quality of SHIP services for low-income beneficiaries. Availability of volunteers was cited as the primary barrier to SHIP services. Topics related to dual eligibility for Medicare and Medicaid were frequently covered in counseling sessions, and staff expressed a desire for more training related to Medicaid and integrated-care programs. Our results suggest that additional counselors and increased training on topics relevant to dually eligible individuals may improve SHIP's ability to provide health insurance-related information to low-income Medicare beneficiaries.
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To determine why SARS-CoV-2 appears to thrive specifically well in meat packaging plants, we used SARS-CoV-2 Delta variant and meat packaging plant drain samples to develop mixed-species biofilms on materials commonly found within meat packaging plants (stainless steel (SS), PVC, and ceramic tile). Our data provides evidence that SARS-CoV-2 Delta variant remained viable on all the surfaces tested with and without an environmental biofilm after the virus was inoculated with the biofilm for 5 days at 7°C. We observed that SARS-CoV-2 Delta variant was able to remain infectious with each of the environmental biofilms by conducting plaque assay and qPCR experiments, however, we detected a significant reduction in viability post-exposure to Plant B biofilm on SS, PVC, and on ceramic tile chips, and to Plant C biofilm on SS and PVC chips. The numbers of viable SARS-CoV-2 Delta viral particles was 1.81-4.57-fold high than the viral inoculum incubated with the Plant B and Plant C environmental biofilm on SS, and PVC chips. We did not detect a significant difference in viability when SARS-CoV-2 Delta variant was incubated with the biofilm obtained from Plant A on any of the materials tested and SARS-CoV-2 Delta variant had higher plaque numbers when inoculated with Plant C biofilm on tile chips, with a 2.75-fold difference compared to SARS-CoV-2 Delta variant on tile chips by itself. In addition, we detected an increase in the biofilm biovolume in response to SARS-CoV-2 Delta variant which is also a concern for food safety due to the potential for foodborne pathogens to respond likewise when they come into contact with the virus. These results indicate a complex virus-environmental biofilm interaction which correlates to the different bacteria found in each biofilm. Our results also indicate that there is the potential for biofilms to protect SARS-CoV-2 from disinfecting agents and remaining prevalent in meat packaging plants.
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Biofilmes , Embalagem de Alimentos , SARS-CoV-2 , Biofilmes/crescimento & desenvolvimento , SARS-CoV-2/fisiologia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/genética , Embalagem de Alimentos/métodos , Humanos , COVID-19/microbiologia , COVID-19/virologia , COVID-19/transmissão , Aço Inoxidável , Carne/microbiologia , Carne/virologiaRESUMO
HER2-positive and triple-negative breast cancers (TNBC) are difficult to treat and associated with poor prognosis. Despite showing initial response, HER2-positive breast cancers often acquire resistance to HER2-targeted therapies, and TNBC lack effective therapies. To overcome these clinical challenges, we evaluated the therapeutic utility of co-targeting TrkA and JAK2/STAT3 pathways in these breast cancer subtypes. Here, we report the novel combination of FDA-approved TrkA inhibitors (Entrectinib or Larotrectinib) and JAK2 inhibitors (Pacritinib or Ruxolitinib) synergistically inhibited in vitro growth of HER2-positive breast cancer cells and TNBC cells. The Entrectinib-Pacritinib combination inhibited the breast cancer stem cell subpopulation, reduced expression of stemness genes, SOX2 and MYC, and induced apoptosis. The Entrectinib-Pacritinib combination suppressed orthotopic growth of HER2-positive Trastuzumab-refractory breast cancer xenografts and basal patient-derived xenograft (PDXs), reduced tumoral SOX2 and MYC, and induced apoptosis in both mouse models. The Entrectinib-Pacritinib combination inhibited overall metastatic burden, and brain and bone metastases of intracardially inoculated TNBC cells without toxicity. Together, our results demonstrate for the first time that co-inhibition of TrkA and JAK2 synergistically suppresses breast cancer growth and metastasis, thereby providing preclinical evidence that supports future clinical evaluations.
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Benzamidas , Janus Quinase 2 , Pirimidinas , Receptor ErbB-2 , Receptor trkA , Neoplasias de Mama Triplo Negativas , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Janus Quinase 2/metabolismo , Janus Quinase 2/antagonistas & inibidores , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Benzamidas/farmacologia , Animais , Feminino , Pirimidinas/farmacologia , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/genética , Linhagem Celular Tumoral , Receptor trkA/metabolismo , Receptor trkA/antagonistas & inibidores , Receptor trkA/genética , Camundongos , Proliferação de Células/efeitos dos fármacos , Indazóis/farmacologia , Pirazóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Camundongos Nus , Sinergismo Farmacológico , Hidrocarbonetos Aromáticos com PontesRESUMO
BACKGROUND: Comanagement of orthopedic surgery patients by internal medicine hospitalists is associated with improvements in clinical outcomes including complications, length of stay, and cost. Clinical outcomes of orthopedic comanagement performed solely by internal medicine advanced practice clinicians have not been reported. Our objecyive was to compare clinical outcomes between advanced practice clinician-based comanagement and usual orthopedic care. METHODS: This is a retrospective cohort study in patients 18 years or older, hospitalized for orthopedic joint or spine surgery between May 1, 2014 and January 1, 2022. Outcomes assessed were length of stay, intensive care unit (ICU) transfer, return to operating room, in-hospital and 30-day mortality, 30-day readmission, and total direct cost, excluding surgical implants. Generalized boosted regression and propensity score weighting was used to compare clinical outcomes and health care cost between usual care and advanced practice clinician comanagement. RESULTS: Advanced practice clinician comanagement was associated with a 5% reduction in mean length of stay (rate ratio = 0.95, P = .009), decreased odds of returning to the operating room (odds ratio [OR] 0.51, P = .002), and a significant reduction in 30-day mortality (OR 0.32, P = .037) compared with usual orthopedic care in a weighted analysis. Need for ICU transfer was higher with advanced practice clinician comanagement (OR 1.54, P = .009), without significant differences in 30-day readmission or in-hospital mortality. CONCLUSIONS: We observed reductions in length of stay, health care costs, return to the operating room, and 30-day mortality with advanced practice clinician comanagement compared with usual orthopedic care. Our findings suggest that advanced practice clinician-based comanagement may represent a safe and cost-effective model for orthopedic comanagement.
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Medicina Interna , Tempo de Internação , Procedimentos Ortopédicos , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Tempo de Internação/estatística & dados numéricos , Procedimentos Ortopédicos/economia , Idoso , Readmissão do Paciente/estatística & dados numéricos , Estudos de Coortes , Mortalidade Hospitalar , Médicos Hospitalares/economia , Unidades de Terapia Intensiva/economiaRESUMO
Specific amino acid footprinting mass spectrometry (MS) is an increasingly utilized method for elucidating protein higher order structure (HOS). It does this by adding to certain amino acid residues a mass tag, whose reaction extent depends on solvent accessibility and microenvironment of the protein. Unlike reactive free radicals and carbenes, these specific footprinters react slower than protein unfolding. Thus, their footprinting, under certain conditions, provokes structural changes to the protein, leading to labeling on non-native structures. It is critical to establish conditions (i.e., reagent concentrations, time of reaction) to ensure that the structure of the protein following footprinting remains native. Here, we compare the efficacy of five methods in assessing protein HOS following footprinting at the intact protein level and then further localize the perturbation at the peptide level. Three are MS-based methods that provide dose-response plot analysis, evaluation of Poisson distributions of precursor and products, and determination of the average number of modifications. These MS-based methods reliably and effectively indicate HOS perturbation at the intact protein level, whereas spectroscopic methods (circular dichroism (CD) and dynamic light scattering (DLS)) are less sensitive in monitoring subtle HOS perturbation caused by footprinting. Evaluation of HOS at the peptide level indicates regions that are sensitive to localized perturbations. Peptide-level analysis also provides higher resolution of the HOS perturbation, and we recommend using it for future footprinting studies. Overall, this work shows conclusive evidence for HOS perturbation caused by footprinting. Implementation of quality control workflows can identify conditions to avoid the perturbation, for footprinting, allowing accurate and reliable identification of protein structural changes that accompany, for example, ligand interactions, mutations, and changes in solution environment.
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Proteínas , Proteínas/química , Espectrometria de Massas , Pegadas de Proteínas/métodos , Conformação Proteica , Aminoácidos/química , Dicroísmo CircularRESUMO
Background: Given the rising prevalence of obesity, the number of patients with obesity undergoing arthroscopic rotator cuff repair (RCR) will likely increase; however, there have been mixed results in the existing literature with regard to the effect of elevated body mass index (BMI) on functional outcomes and complications. Methods: The patient-reported outcome measures included the visual analog scale (VAS) pain score, the American Shoulder and Elbow Surgeons (ASES) score, range of motion, and adverse events. Results: Fourteen studies (118,331 patients) were included. There were significant decreases in VAS pain scores for both patients with obesity (mean difference, -3.8 [95% confidence interval (CI), -3.9 to -3.7]; p < 0.001) and patients without obesity (mean difference, -3.2 [95% CI, -3.3 to -3.1]; p < 0.001). There were also significant increases in ASES scores for both patients with obesity (mean difference, 24.3 [95% CI, 22.5 to 26.1]; p < 0.001) and patients without obesity (mean difference, 24.3 [95% CI, 21.4 to 26.0]; p < 0.001). There were also significant increases in ASES scores for both patients with obesity (mean difference, 24.3 [95% CI, 22.5 to 26.1]; p < 0.001) and patients without obesity (mean difference, 24.3 [95% CI, 21.4 to 26.0]; p < 0.001). However, there were no significant differences in final VAS pain scores, ASES scores, or range of motion between the groups. The mean rates of complications were higher among patients with obesity (1.2% ± 1.7%) than among patients without obesity (0.59% ± 0.11%) (p < 0.0001), and the mean rates of postoperative admissions were also higher among patients with obesity (5.9%) than patients without obesity (3.7%) (p < 0.0001). Although the mean rates of reoperation were similar between groups (5.2% ± 2.8% compared with 5.2% ± 4.2%), the meta-analysis revealed lower odds of reoperation in patients without obesity (odds ratio [OR], 0.76 [95% CI, 0.71 to 0.82]). Conclusions: No significant or clinically important differences in postoperative pain, ASES scores, or range of motion were found between patients with and without obesity following arthroscopic RCR. However, populations with obesity had higher rates of complications, postoperative admissions, and reoperation following arthroscopic RCR. Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
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OBJECTIVE: To investigate the relationship between physician-hospital integration within accountable care organizations (ACOs) and inpatient care utilization and expenditure. DATA SOURCES: The primary data were Massachusetts All-Payer Claims Database (2009-2013). STUDY SETTING: Fifteen provider organizations that entered a commercial ACO contract with a major private payer in Massachusetts between 2009 and 2013. STUDY DESIGN: Using an instrumental variable approach, the study compared inpatient care delivery between patients of ACOs demonstrating high versus low integration. We measured physician-hospital integration within ACOs by the proportion of primary care physicians in an ACO who billed for outpatient services with a place-of-service code indicating employment or practice ownership by a hospital. The study sample comprised non-elderly adults who had continuous insurance coverage and were attributed to one of the 15 ACOs. Outcomes of interest included total medical expenditure during an episode of inpatient care, length of stay (LOS) of the index hospitalization, and 30-day readmission. An inpatient episode was defined as 30, 45, and 60 days from the admission date. DATA COLLECTION/EXTRACTION METHODS: Not applicable. PRINCIPAL FINDINGS: The study examined 33,535 admissions from patients served by the 15 ACOs. Average medical expenditure within 30 days of admission was $24,601, within 45 days was $26,447, and within 60 days was $28,043. Average LOS was 3.5 days, and 5.4% of patients were readmitted within 30 days. Physician-hospital integration was associated with a 10.6% reduction in 30-day expenditure (95% CI, -15.1% to -5.9%). Corresponding estimates for 45 and 60 days were - 9.7% (95%CI, -14.2% to -4.9%) and - 9.6% (95%CI, -14.3% to -4.7%). Integration was associated with a 15.7% decrease in LOS (95%CI, -22.6% to -8.2%) but unrelated to 30-day readmission rate. CONCLUSIONS: Our instrumental variable analysis shows physician-hospital integration with ACOs was associated with reduced inpatient spending and LOS, with no evidence of elevated readmission rates.