RESUMO
Characterizing the mechanisms influencing the distribution of genetic variation in aquatic species can be difficult due to the dynamic nature of hydrological landscapes. In North America's Central Highlands, a complex history of glacial dynamics, long-term isolation, and secondary contact have shaped genetic variation in aquatic species. Although the effects of glacial history have been demonstrated in many taxa, responses are often lineage- or species-specific and driven by organismal ecology. In this study, we reconstruct the evolutionary history of a freshwater mussel species complex using a suite of mitochondrial and nuclear loci to resolve taxonomic and demographic uncertainties. Our findings do not support Pleurobema rubrum as a valid species, which is proposed for listing as threatened under the U.S. Endangered Species Act. We synonymize P. rubrum under Pleurobema sintoxia-a common and widespread species found throughout the Mississippi River Basin. Further investigation of patterns of genetic variation in P. sintoxia identified a complex demographic history, including ancestral vicariance and secondary contact, within the Eastern Highlands. We hypothesize these patterns were shaped by ancestral vicariance driven by the formation of Lake Green and subsequent secondary contact after the last glacial maximum. Our inference aligns with demographic histories observed in other aquatic taxa in the region and mirrors patterns of genetic variation of a freshwater fish species (Erimystax dissimilis) confirmed to serve as a parasitic larval host for P. sintoxia. Our findings directly link species ecology to observed patterns of genetic variation and may have significant implications for future conservation and recovery actions of freshwater mussels.
Assuntos
Bivalves , DNA Mitocondrial , Animais , DNA Mitocondrial/genética , Espécies em Perigo de Extinção , Bivalves/genética , Lagos , Demografia , Filogenia , Variação GenéticaRESUMO
A fundamental question in developmental biology is whether tissue architectures formed during development are set for life, or require continuous maintenance signals, and if so, what are those signals. The islets of Langerhans in the pancreas can serve as an elegant model tissue to answer these questions. Islets have a non-random spatial architecture, which is important to proper glucose homeostasis. Islet architecture forms during embryonic development, in a morphogenesis process partially involving expression of Roundabout (Robo) receptors in ß cells, and their ligand, Slit, in the surrounding mesenchyme. Whether islet architecture is set during development and remains passive in adulthood, or whether it requires active maintenance throughout life, has not been determined. Here we conditionally deleted Robo2 in ß cells of adult mice and observed their islet architecture following a two-month chase. We show that deleting Robo2 in adult ß cells causes significant loss of islet architecture without affecting ß cell identity, maturation, or stress, indicating that Robo2 plays a role in actively maintaining adult islet architecture. Understanding the factors required to maintain islet architecture, and thus optimize islet function, is important for developing future diabetes therapies.
Assuntos
Células Secretoras de Insulina , Ilhotas Pancreáticas , Camundongos , Animais , Pâncreas , Morfogênese , Ilhotas Pancreáticas/metabolismo , Proteínas Roundabout , Receptores Imunológicos/fisiologiaRESUMO
BACKGROUND: The body's anatomical position can influence the autonomic response to return to homeostasis following high intensity exercise. Discrepancies exist as to which body position is considered optimal and practical. This study intends to examine three recovery positions post submaximal exercise to determine which body position would be the most efficient in terms of excess post-exercise oxygen consumption and heart rate recovery. METHODS: NCAA Division I athletes (N.=17) from multiple sport teams completed three submaximal exercise tests utilizing the Bruce Protocol. Excess post-exercise oxygen consumption and heart rate recovery were measured at peak exercise and at 1-, 5-, and 10-minute time intervals during the recovery phase while assuming a recovery position: supine, trunk forward leaning, and standing vertical. RESULTS: Statistical analysis showed the 1-minute excess post-exercise oxygen consumption associated with supine recovery (1725±348 mL/kg) was significantly greater than standing vertical (1578±340 mL/kg, P=0.024). At 5 minutes, supine excess post-exercise oxygen consumption (3557±760 mL/kg) was significantly less than trunk forward leaning (4054±777 mL/kg, P=0.0001) and trunk forward leaning was significantly greater than standing vertical (3776±700 mL/kg, P=0.008). At 10 minutes, supine excess post-exercise oxygen consumption (5246±961 mL/kg) was significantly less than both the standing vertical position (5878±1042 mL/kg, P=0.0099), and the trunk forward leaning position (6749±1223 mL/kg, P<0.0001). Supine had the highest heart rate recovery at 1-, 5-, and 10-minutes post exercise. CONCLUSIONS: The supine position proved to be the most optimal during the 10-minute recovery period, while the trunk forward leaning position showed to be a more advantageous position for short-term recovery.
Assuntos
Coração , Postura , Humanos , Postura/fisiologia , Teste de Esforço , Exercício Físico/fisiologia , Frequência Cardíaca/fisiologia , Atletas , Decúbito Dorsal/fisiologiaRESUMO
OBJECTIVE: To. determine the impact of 5-α reductase inhibitors or α-blockers on IsoPSA performance for the detection of actionable prostate cancer. MATERIALS AND METHODS: This is a secondary analysis of data from an institutional review board approved, prospective, multicenter(8-sites) study evaluating IsoPSA in men ≥ 50 years of age with a total PSA ≥ 4 ng/mL with planned prostate biopsy who met previously described inclusion and exclusion criteria. Analytic groups included (i)all subjects, (ii-iii)+/- 5-ARI use, (iv-v)+/- α-blocker use. The performance characteristics of IsoPSA in these groups were assessed by ROC curve, sensitivity, and specificity (SP) analysis. RESULTS: A total of 1385 men were recruited with 888 men included in final analysis. Actionable prostate cancer, defined as GG2+, was identified in a total of 316 patients with 40 and 217 patients reporting 5-ARI and α-blocker use respectively. Sensitivity to detect both prostate cancer and actionable cancer was similar between patient subsets (P >.05). SP was similar between patients regardless of 5-ARI(P >.05). Increased SP was noted in patients on α-blockers(GG1+: No-α-blocker: 0.360 vs α-blocker: 0.529, P <.05; GG2+: No-α-blocker: 0.40 vs α-blocker: 0.61, P <.05). ROC analysis demonstrates that IsoPSA performance is unaffected by 5-ARI or α-blocker use for prostate cancer and actionable cancer (GG2+) detection. CONCLUSION: The performance of IsoPSA for detecting any prostate cancer and clinically actionable prostate cancer is unaffected by commonly used medications (5-ARI and α-blockers) for symptoms of benign prostatic hyperplasia.
Assuntos
Hiperplasia Prostática , Neoplasias da Próstata , Masculino , Humanos , Inibidores de 5-alfa Redutase/uso terapêutico , Antígeno Prostático Específico , Estudos Prospectivos , Neoplasias da Próstata/patologia , Hiperplasia Prostática/complicações , Antagonistas Adrenérgicos alfa/uso terapêuticoRESUMO
Objectives: To compare overall agreement between magnetic resonance imaging (MRI)-ultrasound (US) fusion biopsy (FB) and MRI cognitive fusion biopsy (CB) of the prostate and determine which factors affect agreement for prostate cancer (PCa) who underwent both modalities in a prospective within-patient protocol. Patients and Methods: From August 2017 to January 2021, patients with at least one Prostate Imaging Reporting & Data System (PI-RADS) 3 or higher lesion on multiparametric MRI underwent transrectal FB and CB in a prospective within-patient protocol. CB was performed for each region of interest (ROI), followed by FB, followed by standard 12 core biopsy. Patients who were not on active surveillance were analysed. The primary endpoint was agreement for any PCa detection. McNemar's test and kappa statistic were used to analyse agreement. Chi-square test, Fisher's exact test and Wilcoxon rank sum test were used to analyse disagreement across clinical and MRI spatial variables. A multivariable generalized mixed-effect model was used to compare the interaction between select variables and fusion modality. Statistics were performed using SAS and R. Results: Ninety patients and 98 lesions were included in the analysis. There was moderate agreement between FB and CB (k = 0.715). McNemar's test was insignificant (p = 0.285). Anterior location was the only variable associated with a significant variation in agreement, which was 70% for anterior lesions versus 89.7% for non-anterior lesions (p = 0.035). Discordance did not vary significantly across other variables. In a mixed-effect model, the interaction between anterior location and use of FB was insignificant (p = 0.411). Conclusion: In a within-patient protocol of patients not on active surveillance, FB and CB performed similarly for PCa detection and with moderate agreement. Anterior location was associated with significantly higher disagreement, whereas other patient and lesion characteristics were not. Additional studies are needed to determine optimal biopsy technique for sampling anterior ROI.
RESUMO
BACKGROUND: IsoPSA is a blood-based test that assesses prostate cancer (CaP) risk by partitioning and detecting cancer-specific structural isoforms of prostate specific antigen (PSA) with an aqueous 2- phase system. OBJECTIVE: To validate the diagnostic performance of IsoPSA for High-Grade CaP and Any CaP risk on biopsy in men age ≥ 50 with total PSA ≥ 4 ng/ml. DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter study of 888 men scheduled for prostate biopsy at 8 academic and community sites between August 2015 and August 2020. INTERVENTION: IsoPSA test. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Receiver operating characteristic and likelihood ratio analysis used to validate diagnostic performance for previously established IsoPSA Index cutoffs for High-Grade CaP (Gleason Score ≥ 7) and Any CaP (Gleason Score ≥ 6), compare IsoPSA to total PSA and % free PSA, and evaluate subgroups (total PSA 4-10 ng/ml, total PSA > 10 ng/ml, biopsy naïve, prior negative biopsy). RESULTS AND LIMITATIONS: The disease prevalence was 35.6% (High-Grade CaP) and 58.9% (Any CaP). The area under the receiver operating characteristic curve was 0.783 (High-Grade CaP) and 0.770 (Any CaP). IsoPSA outperformed total PSA and % free PSA on area under the receiver operating characteristic curve, specificity, positive and negative predictive value at similar sensitivity. Using selected IsoPSA Index cutoffs, an estimated 46% (High-Grade CaP) and 42% (Any CaP) of biopsies could be avoided in low-risk patients. IsoPSA displayed statistically informative likelihood ratio-based predictive characteristics. IsoPSA maintained accuracy in clinically relevant subgroups. CONCLUSIONS: IsoPSA diagnostic performance and predictive value is validated for High-Grade CaP and Any CaP in men age ≥ 50 with total PSA ≥ 4 ng/ml undergoing diagnostic biopsy. IsoPSA outperforms total and % free PSA in discriminating the risk of prostate cancer on biopsy. PATIENT SUMMARY: IsoPSA has the potential to reduce unnecessary biopsies and improve the risk-benefit ratio for CaP early detection.
Assuntos
Antígeno Prostático Específico , Neoplasias da Próstata , Biópsia , Humanos , Masculino , Gradação de Tumores , Estudos Prospectivos , Próstata , Curva ROCRESUMO
BACKGROUND: Historically, the treatment of iliac artery occlusive disease required a surgical bypass usually consisting of an aortobifemoral bypass or an iliofemoral bypass. With the advent of balloon angioplasty and stenting, these procedures are frequently replaced with endovascular options. However, the treatment of diffuse occlusive disease of the external iliac artery (EIA) using balloon angioplasty and/or stenting does not carry a favorable long-term patency rate. Remote endarterectomy of the EIA using ring dissectors with balloon assistance provides a novel, controlled, safe, and durable treatment of the diseased and/or occluded EIA. METHODS: A retrospective review over the past 6 years was performed at our institution identifying patients treated with balloon-assisted remote endarterectomy of the EIA by the current five practicing vascular surgeons. The technique involves exposure of the ipsilateral common femoral artery. With nonocclusive disease, direct access into the common femoral artery is performed, a wire is traversed through the diseased EIA, and a balloon is inflated at the origin of the vessel providing hemostasis and control. A femoral endarterectomy is performed, and a ring dissector is passed over the endarterectomized material including the wire and balloon catheter and advanced remotely through the EIA up to the balloon. The balloon is briefly deflated, repositioned within the ring dissector, and reinflated, thus cutting the plaque. This allows for retraction of the inflated balloon and cutter, removing the endarterectomized core plaque. The procedure is similar for the treatment of an occluded EIA, but wire access across the occluded vessel is normally achieved with contralateral access. In both cases, the balloon provides control and hemostasis and is critically important in the rare treatment of vessel rupture. RESULTS: A total of 101 vessels were treated in 97 patients. The procedure was successful in 98 vessels (97%) with failure related to vessel rupture requiring conversion to an iliofemoral bypass. The estimated patency rate at three years was 94% with a median follow-up of 20 months. Restenosis/occlusion in four patients seemed to be related to a severe sclerotic response. The EIA was occluded 32% of the time. The common iliac artery (CIA) was diseased requiring angioplasty and stenting 29% of the time and a stent was placed at the transition zone between endarterectomized vessel and nontreated proximal most EIA or distal most CIA 58% of the time. There were no perioperative deaths. CONCLUSIONS: Balloon-assisted remote endarterectomy of the diffusely diseased and/or occluded EIA is a safe and durable option. It precludes the need for a prosthetic conduit and the risk of associated infection. It also involves a single groin incision and negates the need for retroperitoneal exposure of the CIA.
Assuntos
Angioplastia com Balão , Arteriopatias Oclusivas/terapia , Endarterectomia , Artéria Ilíaca/cirurgia , Idoso , Angioplastia com Balão/efeitos adversos , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/fisiopatologia , Terapia Combinada , Endarterectomia/efeitos adversos , Feminino , Humanos , Artéria Ilíaca/diagnóstico por imagem , Artéria Ilíaca/fisiopatologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/cirurgia , Recidiva , Reoperação , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução VascularAssuntos
Aorta Torácica/cirurgia , Fator VIIa/administração & dosagem , Hemostáticos/administração & dosagem , Hemorragia Pós-Operatória/tratamento farmacológico , Idoso , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Procedimentos Cirúrgicos Cardiovasculares , Relação Dose-Resposta a Droga , Fator VIIa/efeitos adversos , Feminino , Hemostáticos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Estudos Retrospectivos , Tromboembolia/induzido quimicamenteAssuntos
Guias como Assunto , Infecções Fúngicas Invasivas/terapia , Triagem/métodos , Adulto , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Área Sob a Curva , Teorema de Bayes , Técnicas de Apoio para a Decisão , Humanos , Infecções Fúngicas Invasivas/diagnóstico , Escores de Disfunção Orgânica , Curva ROC , GuerraRESUMO
BACKGROUND: Proximal thoracic aortic surgery utilizing hypothermic circulatory arrest carries risks of mortality and major morbidity; however, these risks are not the same for every patient. The goal of the current study was to establish a risk prediction model for risk-stratifying patients undergoing proximal thoracic aortic surgery with hypothermic circulatory arrest for degenerative pathology, to facilitate preoperative physician-patient counseling. METHODS: A retrospective analysis was conducted on 489 patients who underwent proximal thoracic aortic surgery with hypothermic circulatory arrest for degenerative pathology between July 2005 and August 2014 at a single referral institution; patients with acute dissection (n = 139) were excluded. Multivariable logistic regression was used to build a risk prediction model and identify preoperative predictors of major adverse outcome-the composite endpoint of 30-day/inhospital mortality, stroke, acute renal failure, prolonged ventilation, or discharge to a location other than home. The results were validated using an independent cohort of 120 patients operated on from September 2014 to September 2016. RESULTS: Multivariable analysis identified age (p = 0.0002, odds ratio [OR] 2.01), total arch replacement (p ≤ 0.0001, OR 6.75), and procedure status (p = 0.0028; OR 2.73 for urgent, OR 43.58 for emergent) as independent predictors associated with major adverse outcome. The calibration curve for probability of major adverse outcome showed excellent agreement between the model and observations. The concordance index was 0.93 in external validation. CONCLUSIONS: The current study identified risk factors for major adverse outcome after proximal thoracic aortic surgery with hypothermic circulatory arrest for degenerative pathology. The proposed simple, accurate model can quantify risk and facilitate physician-patient counseling before possible surgical intervention.
Assuntos
Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Hipotermia Induzida/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Medição de Risco/métodos , Procedimentos Cirúrgicos Torácicos/efeitos adversos , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Procedimentos Cirúrgicos Torácicos/métodosRESUMO
OBJECTIVE: To assess the relative contributions of patient and surgeon factors for predicting selection of ileal conduit (IC), neobladder (NB), or continent pouch (CP) urinary diversions (UD) for patients diagnosed with muscle-invasive/high-risk nonmuscle invasive bladder cancer. This information is needed to enhance research comparing cancer survivors' outcomes across different surgical treatment options. METHODS: Bladder cancer patients' age ≥21 years with cystectomy/UD performed from January 2010 to June 2015 in 3 Kaiser Permanente regions were included. All patient and surgeon data were obtained from electronic health records. A mixed effects logistic regression model was used treating surgeon as a random effect and region as a fixed effect. RESULTS: Of 991 eligible patients, 794 (80%) received IC. One hundred sixty-nine surgeons performed the surgeries and accounted for a sizeable proportion of the variability in patient receipt of UD (intraclass correlation coefficientâ¯=â¯0.26). The multilevel model with only patient factors showed good fit (area under the curveâ¯=â¯0.93, Hosmer-Lemeshow test Pâ¯=â¯.44), and older age, female sex, estimated glomerular filtration rate <45, 4+ comorbidity index score, and stage III/IV tumors were associated with higher odds of receiving an IC vs neobladder/continent pouch. However, including surgeon factors (annual cystectomy volume, specialty training, clinical tenure) had no association (Pâ¯=â¯.29). CONCLUSION: In this community setting, patient factors were major predictors of UD received. Surgeons also played a substantial role, yet clinical training and experience were not major predictors. Surgeon factors such as beliefs about UD options and outcomes should be explored.
Assuntos
Cistectomia , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária , Idoso , Serviços de Saúde Comunitária , Prestação Integrada de Cuidados de Saúde , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Seleção de Pacientes , Complicações Pós-Operatórias/epidemiologia , Neoplasias da Bexiga Urinária/patologia , Derivação Urinária/métodos , Derivação Urinária/estatística & dados numéricosRESUMO
Adenoid cystic carcinoma of the Bartholin Gland (BG-ACC) is a rare form of vulval cancer with only approximately 350 reported cases since 1864. A review of available literature and case reports suggests an aggressive nature with protracted clinical symptoms and a tendency for local recurrence despite adequate surgical excision with or without adjuvant radiotherapy. Survival rates of 71% and 59% are reported at five and ten years. This case report endeavours to add to our body of knowledge regarding this rare disease and thus help broaden and improve our understanding of management and treatment success.
Assuntos
Implante de Prótese Vascular/efeitos adversos , Prótese Vascular/efeitos adversos , Embolia/etiologia , Migração de Corpo Estranho/etiologia , Falência Renal Crônica/terapia , Falha de Prótese , Diálise Renal , Implante de Prótese Vascular/instrumentação , Embolia/diagnóstico por imagem , Embolia/terapia , Migração de Corpo Estranho/diagnóstico por imagem , Migração de Corpo Estranho/terapia , Humanos , Falência Renal Crônica/diagnóstico , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Resultado do TratamentoRESUMO
Using an untargeted metabolomics approach in initial (N = 99 subjects) and replication cohorts (N = 1,162), we discovered and structurally identified a plasma metabolite associated with cardiovascular disease (CVD) risks, N6,N6,N6-trimethyl-L-lysine (trimethyllysine, TML). Stable-isotope-dilution tandem mass spectrometry analyses of an independent validation cohort (N = 2,140) confirmed TML levels are independently associated with incident (3-year) major adverse cardiovascular event risks (hazards ratio [HR], 2.4; 95% CI, 1.7-3.4) and incident (5-year) mortality risk (HR, 2.9; 95% CI, 2.0-4.2). Genome-wide association studies identified several suggestive loci for TML levels, but none reached genome-wide significance; and d9(trimethyl)-TML isotope tracer studies confirmed TML can serve as a nutrient precursor for gut microbiota-dependent generation of trimethylamine (TMA) and the atherogenic metabolite trimethylamine N-oxide (TMAO). Although TML was shown to be abundant in both plant- and animal-derived foods, mouse and human fecal cultures (omnivores and vegans) showed slow conversion of TML to TMA. Furthermore, unlike chronic dietary choline, TML supplementation in mice failed to elevate plasma TMAO or heighten thrombosis potential in vivo. Thus, TML is identified as a strong predictor of incident CVD risks in subjects and to serve as a dietary precursor for gut microbiota-dependent generation of TMAO; however, TML does not appear to be a major microbial source for TMAO generation in vivo.
Assuntos
Doenças Cardiovasculares/metabolismo , Lisina/análogos & derivados , Metabolômica , Metilaminas/metabolismo , Nutrientes/metabolismo , Idoso , Animais , Aterosclerose/metabolismo , Carnitina , Colesterol/metabolismo , Colina , Modelos Animais de Doenças , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal , Estudo de Associação Genômica Ampla , Humanos , Lisina/sangue , Lisina/genética , Lisina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Fatores de Risco , TromboseRESUMO
BACKGROUND: The optimal surgical approach for management of acute type A aortic dissection remains controversial. This study aimed to assess outcomes of reoperation after acute type A dissection repair to help guide decision making around index operative strategy. METHODS AND RESULTS: All aortic reoperations (n=129) at a single referral institution from August 2005 to April 2016 after prior acute type A dissection repair were reviewed. The primary outcome was 30-day or in-hospital mortality. Secondary outcomes included organ-specific morbidity and 1- and 5-year outcomes as estimated using the Kaplan-Meier method. The majority of initial reoperations were proximal aortic (aortic valve, aortic root, or ascending) or aortic arch procedures (62.5%, n=55); most initial reoperations were performed in the elective setting (83.1%, n=74). Additional nonstaged second or more reoperations were required in 21 patients (23.6%) after the initial reoperation, during a median follow-up of 2.5 years after the initial reoperation. Thirty-day or in-hospital mortality for all reoperations was 7.0% (elective: 6.3%; nonelective: 11.1%) with acceptable rates of organ-specific morbidity, given the procedural complexity. One- and 5-year overall survival after initial reoperation was 85.9% and 64.9%, respectively, with aorta-specific survival of 88% at 5 years. CONCLUSIONS: Reoperation after acute type A aortic dissection repair is associated with low rates of mortality and morbidity. These data support more limited index repair for acute type A dissection, especially for patients undergoing index repair in lower volume centers without expertise in extensive repair, because reoperations, if needed, can be performed safely in referral aortic centers.
Assuntos
Aneurisma Aórtico/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Complicações Pós-Operatórias/cirurgia , Doença Aguda , Idoso , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/mortalidade , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/mortalidade , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Tomada de Decisão Clínica , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , North Carolina , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/mortalidade , Reoperação , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Increased circulating levels of apolipoprotein A-I (apoA-I), the major protein of high-density lipoprotein (HDL), by genetic manipulation or infusion, protects against melanoma growth and metastasis. Herein, we explored potential roles in melanoma tumorigenesis for host scavenger receptor class B, type 1 (SR-B1), and ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1), all mediators of apoA-I and HDL sterol and lipid transport function. In a syngeneic murine melanoma tumor model, B16F10, mice with global deletion of SR-B1 expression exhibited increased plasma HDL cholesterol (HDLc) levels and decreased tumor volume, indicating host SR-B1 does not directly contribute to HDL-associated anti-tumor activity. In mice with myeloid-specific loss of ABCA1 (Abca1-M/-M ; A1-M/-M), tumor growth was inhibited by â¼4.8-fold relative to wild type (WT) animals. Abcg1-M/-M (G1-M/-M) animals were also protected by 2.5-fold relative to WT, with no further inhibition of tumor growth in Abca1/Abcg1 myeloid-specific double knockout animals (DKO). Analyses of tumor-infiltrating immune cells revealed a correlation between tumor protection and decreased presence of the immune suppressive myeloid-derived suppressor cell (MDSC) subsets, Ly-6G+Ly-6CLo and Ly-6GnegLy-6CHi cells. The growth of the syngeneic MB49 murine bladder cancer cells was also inhibited in A1-M/-M mice. Collectively, our studies provide further evidence for an immune modulatory role for cholesterol homeostasis pathways in cancer.
RESUMO
OBJECTIVE: To describe the incidence of difficult and failed intubations in obstetric patients during a 6 year period monitored by a quality assurance program together with American Society of Anesthesiologists Physical Status (ASA PS) scores, and obesity (body mass index >30 kg/m2). METHODS: Following Institutional Review Board approval, data about obstetric patients who experienced unanticipated difficult or failed intubations from 2010 to 2015 was obtained from the quality assurance database of a large, community-based anesthesiology group practice. The database employs standardized definitions for difficult intubation (>3 laryngoscopic attempts by experienced providers) and failed intubation (inability to intubate leading to surgical airway or waking up the patient). ASA PS scores and comorbidities were also identified for obstetric general anesthetics using an internally developed quality assurance program, Quantum Clinical Navigation System. RESULTS: There were 2802 obstetric general anesthetics in the database of which 1085 (38.7%) were deemed as emergencies. There were no cases of failed intubation and seven cases of unanticipated difficult intubations (1:400 cases, 0.25% of all obstetric general anesthetics, 95% confidence interval 0.1-0.5%), six of which occurred during emergency surgery. There was an increase in obesity (p = .003) and ASA PS (p = .02) over the period of the study. The incidence of difficult intubation was not found to be significantly changed (p = .68). CONCLUSIONS: Despite an increase in ASA PS score and obesity, there was no increase in the incidence of difficult intubation in obstetric patients. Limitations of the study include its retrospective design, and the small number of difficult intubation cases identified.
Assuntos
Intubação Intratraqueal , Feminino , Humanos , Incidência , Masculino , Gravidez , Prevalência , Estudos RetrospectivosRESUMO
BACKGROUND: Total joint arthroplasty (TJA) is one of the most successful operations. There is little in the literature regarding weight change following TJA, particularly in a young cohort. METHODS: Retrospective analysis of 181 primary total hip arthroplasty (THA) and 185 primary total knee arthroplasty (TKA) patients was conducted. We reviewed preoperative and post-operative weights and post-operative body mass index at 3 and 6 months, 1 year, 2 and 3 years. We evaluated expected versus actual weight gain, and performed subgroup analyses of obese versus non-obese patients and active duty versus civilian patients. We used a minimal clinically meaningful weight change from baseline of ≥5%. RESULTS: One hundred and fifty-one (41.3%) patients were active duty military service members with the mean age of 53 ± 11.1 years. In TKA patients, statistically significant differences were found in mean weights at 3 months (-1.8%, P ≤ 0.0001) and 2 years (+1.9%, P = 0.0006). In THA patients, statistically significant weight gains were found at 6 months (+1.1%, P = 0.006). For obese TKA patients, significant weight changes were observed at 3 months (-2.5%, P ≤ 0.0001), and none in the obese THA group. There were no statistical or clinically meaningful weight changes in the non-obese TKA or THA groups. There was a clinically meaningful weight gain in active duty TKA patients at 3 years (5.18%, P = 0.17). CONCLUSION: Despite a theoretical ability to lose weight following TJA, patients maintain their preoperative weight following TJA. We found a clinically meaningful weight gain at 3 years post-operatively only in active duty TKA patients. Overall, however, we found no clinically significant weight changes following TJA at 3-year follow-up.
Assuntos
Artroplastia do Joelho , Índice de Massa Corporal , Osteoartrite do Joelho/cirurgia , Redução de Peso/fisiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/fisiopatologia , Período Pós-Operatório , Estudos Retrospectivos , Fatores de TempoRESUMO
The data presented in this article are related to the research article, "HPLC-based enzyme kinetics assay for glucosinolate hydrolysis facilitate analysis of systems with both multiple reaction products and thermal enzyme denaturation" (C.K. Klingaman, M.J. Wagner, J.R. Brown, J.B. Klecker, E.H. Pauley, C.J. Noldner, J.R. Mays,) [1]. This data article describes (1) the synthesis and spectral characterization data of a non-natural glucosinolate analogue, 2,2-diphenylethyl glucosinolate, (2) HPLC standardization data for glucosinolate, isothiocyanate, nitrile, and amine analytes, (3) reaction progress curve data for enzymatic hydrolysis reactions with variable substrate concentration, enzyme concentration, buffer pH, and temperature, and (4) normalized initial velocities of hydrolysis/formation for analytes. These data provide a comprehensive description of the enzyme-catalyzed hydrolysis of 2,2-diphenylethyl glucosinolate (5) and glucotropaeolin (6) under widely varied conditions.