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Here, we demonstrate a fundamentally new reactivity of the silyl enol ether functionality utilizing an in situ-generated iodonitrene-like species. The present transformation inserts a nitrogen atom between the silyl enol ether olefinic carbons with the concomitant cleavage of the CâC bond. Overall, this facile transformation converts a C-nucleophilic silyl enol ether to the corresponding C-electrophilic N-acyl-N,O-acetal. This unprecedented access to α-amido alkylating agents enables modular derivatization with carbon and heteroatom nucleophiles and the unique late-stage editing of carbon frameworks. The reaction efficiency of this transformation is well correlated with enol ether nucleophilicity as described by the Mayr N scale. Applications presented herein include late-stage nitrogen insertion into carbon skeletons of natural products with previously unattainable regioselectivity as well as modified conditions for 15N labeling of amides and lactams.
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OBJECTIVE: Within the past decade, Medicare Part B reimbursements for various surgical procedures have been declining, whereas health care expenses continue to increase. As a result, hospitals may increase service charges to offset losses in revenue, which may disproportionately affect underinsured patients. Our analysis aimed to characterize Medicare billing and utilization trends across common vascular surgical procedures. METHODS: The 2017 to 2021 Medicare Physician and Other Practitioners by Provider and Service dataset was queried for Current Procedural Terminology (CPT) codes for common vascular surgery procedures. The average charges, reimbursements, charge-to-reimbursement ratios, and service counts were calculated for the most common interventions performed by vascular surgeons. Data was stratified by care setting, facility (inpatient and outpatient hospital) vs non-facility locations. All monetary values were adjusted to the 2021 United States dollars to account for inflation. RESULTS: For facility settings, the mean charge billed to Medicare Part B increased from $3708 to $3952 (6.6%) from 2017 to 2021, with the average charge-to-reimbursement ratio increasing from 7.2 to 8.6. There were 17 of the 19 facility procedures that had a decline in reimbursements, decreasing from an average of $558 to $499 (-10.4%). Stab phlebectomy had the largest individual decrease in facility reimbursement (-53.5%), followed by above-knee amputation (-11.3%) and below-knee amputation (-11.0%). Both non-facility charges (-10.8%) and reimbursements (-12.2%) declined over the study period. Procedural utilization remained stable from 2017 to 2019. Tibial and femoral-popliteal atherectomy had increases of 45.9% and 33.7%, respectively, in overall procedural utilization when performed in non-facility settings from 2017 to 2019. CONCLUSIONS: Our analysis of vascular surgery procedures billed to Medicare Part B from 2017 to 2021 demonstrates an increase in charges, a decline in reimbursements, and a resultant increase in charge-to-reimbursement ratios for facility care settings. In contrast, non-facility charges have decreased in the face of declining reimbursements. These markups in submitted charges in facility locations may serve as an additional barrier to accessing care for patients who are underinsured.
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Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between JAK2V617F allele burden (also known as variant allele frequency) and the relevant clinical characteristics. Numerous studies have reported associations between allele burden and both hematologic and clinical features. While there are strong indications linking high allele burden in PV patients with symptoms and clinical characteristics, not all associations are definitive, and disparate and contradictory findings have been reported. Hence, this study aimed to synthesize existing data from the literature to better understand the association between JAK2V617F allele burden and relevant clinical correlates. Out of the 1,851 studies identified, 39 studies provided evidence related to the association between JAK2V617F allele burden and clinical correlates, and 21 studies were included in meta-analyses. Meta-analyses of correlation demonstrated that leucocyte and erythrocyte counts were significantly and positively correlated with JAK2V617F allele burden, whereas platelet count was not. Meta-analyses of standardized mean difference demonstrated that leucocyte and hematocrit were significantly higher in patients with higher JAK2V617F allele burden, whereas platelet count was significantly lower. Meta-analyses of odds ratio demonstrated that patients who had higher JAK2V617F allele burden had a significantly greater odds ratio for developing pruritus, splenomegaly, thrombosis, myelofibrosis, and acute myeloid leukemia. Our study integrates data from approximately 5,462 patients, contributing insights into the association between JAK2V617F allele burden and various hematological parameters, symptomatic manifestations, and complications. However, varied methods of data presentation and statistical analyses prevented the execution of high-quality meta-analyses.
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Alelos , Janus Quinase 2 , Policitemia Vera , Policitemia Vera/genética , Policitemia Vera/sangue , Janus Quinase 2/genética , Humanos , Frequência do Gene , Substituição de Aminoácidos , Mutação de Sentido IncorretoRESUMO
While single-segment great saphenous vein (GSV) remains the gold-standard conduit for infrainguinal bypass, several alternative options are available for use when GSV is absent in patients with chronic limb threatening ischemia requiring infrainguinal revascularization including alternative autologous vein, prosthetic conduits, and cryopreserved vein grafts.
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Implante de Prótese Vascular , Prótese Vascular , Extremidade Inferior , Doença Arterial Periférica , Humanos , Extremidade Inferior/irrigação sanguínea , Resultado do Tratamento , Doença Arterial Periférica/cirurgia , Doença Arterial Periférica/fisiopatologia , Doença Arterial Periférica/diagnóstico por imagem , Implante de Prótese Vascular/instrumentação , Implante de Prótese Vascular/efeitos adversos , Grau de Desobstrução Vascular , Criopreservação , Veia Safena/transplante , Transplante Autólogo , Veias/transplante , Veias/cirurgia , Veias/diagnóstico por imagem , Isquemia Crônica Crítica de Membro/cirurgia , Fatores de Risco , Isquemia/cirurgia , Isquemia/fisiopatologia , Isquemia/diagnóstico por imagemRESUMO
We present APAC-Net, an alternating population and agent control neural network for solving stochastic mean-field games (MFGs). Our algorithm is geared toward high-dimensional instances of MFGs that are not approachable with existing solution methods. We achieve this in two steps. First, we take advantage of the underlying variational primal-dual structure that MFGs exhibit and phrase it as a convex-concave saddle-point problem. Second, we parameterize the value and density functions by two neural networks, respectively. By phrasing the problem in this manner, solving the MFG can be interpreted as a special case of training a generative adversarial network (GAN). We show the potential of our method on up to 100-dimensional MFG problems.
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PURPOSE: The impact of body mass index (BMI) on patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU) is controversial. Increasing evidence suggests an age-dependent relationship between obesity and outcomes for some solid organ tumors. Herein, we aimed to assess the prognostic value of preoperative BMI in UTUC patients treated with RNU in Taiwan. METHODS: This was a retrospective single-center study of 468 UTUC patients undergoing RNU during January 2010-December 2017, with preoperative BMI classification and subgroup analysis based on ages of < or ≥ 70 years. All UTUC patients underwent RNU and bladder cuff excision. Overall survival (OS), cancer-specific survival, and disease-free survival (DFS) were analyzed. Fisher's exact test, Mann-Whitney U test, Kaplan-Meier method, and Cox regression model were used for data analysis. RESULTS: The median follow-up duration was 36 months. Patients with higher versus lower BMI (cutoff: 25 kg/m2) showed no differences in OS; older patients had poor OS (hazard ratio [HR] 1.74; 95% confidence interval [CI] 1.24-2.40; p < 0.001). Older age was an independent predictor of poor OS in multivariate Cox regression analysis (p = 0.001). Younger patients with higher BMI (p = 0.02) had better DFS than older patients with no BMI-related survival differences. Higher BMI was an independent predictor of favorable DFS in younger patients in multivariate Cox regression analysis (HR, 0.53; 95% CI 0.28-0.99; p = 0.043). CONCLUSION: Younger UTUC patients with higher BMI were independently associated with a favorable DFS.
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Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Humanos , Nefroureterectomia , Carcinoma de Células de Transição/patologia , Índice de Massa Corporal , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias Ureterais/cirurgia , Prognóstico , Neoplasias Renais/cirurgia , Pelve Renal/patologia , Neoplasias Urológicas/patologiaRESUMO
This Asia-Pacific (AP) AMS 800™ artificial urinary sphincter (AUS) consensus statement aims to provide a set of practical recommendations to assist surgeons with the AMS 800 device surgery. The AP consensus committee consisted of key opinion leaders with extensive experience with AMS 800 surgery across several AP countries. The panel reviewed and discussed relevant findings with emphasis on locoregional and specific clinical challenges relevant to the AP region. Recommendations were made in key areas namely (1) patient selection and informed consent process; (2) preoperative assessment; (3) dealing with co-existing urological disorders; (4) surgical principles and intraoperative troubleshooting; (5) postoperative care; (6) special populations; and (7) cost analysis and comparative review. The AMS 800 device should be offered to males with moderate to severe stress urinary incontinence (SUI). Full informed consent should be undertaken, and emphasis is placed on surgical contraindications and high-risk candidates. The presence of a surgical mentor or referral to experts is recommended in complex AUS candidates. Preoperative cystoscopy with or without multichannel urodynamic study is necessary and patients with pre-existing urological disorders should be treated adequately and clinically stable before surgery. Adherence to strict patient selection and safe surgical principles are critical to ensure excellent clinical outcomes and minimize complications. Given that InhibiZone-coated device is not available in many AP countries, the use of prophylactic antibiotics pre-and post-operatively are recommended. The AMS 800 device should be prepared according to the manufacturer's guidelines and remains a cost-effective treatment for male SUI. The AMS 800 device remains the surgical benchmark for male SUI but is associated with certain mechanical limitations and a unique set of complications.
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Incontinência Urinária por Estresse , Esfíncter Urinário Artificial , Humanos , Masculino , Incontinência Urinária por Estresse/cirurgia , Resultado do Tratamento , Cuidados Pós-Operatórios , ÁsiaRESUMO
This study was designed to examine the use of pharmacogenomics (PGx) testing in a community-based facility, the adoption of the PGx recommendations by providers, and assess challenges and opportunities for pharmacists in using PGx testing in a real-world setting. This was a retrospective study involving chart reviews of 137 patients with mood disorders who underwent PGx testing between September 2017 and December 2017. Eighty-seven patients who met inclusion and exclusion criteria were analyzed to evaluate the impact of PGx testing on psychotropic medication treatment and to evaluate the PGx test process. PGx test results were used by providers to guide their therapeutic modifications based on the gene-drug interactions identified. Patient medication use increased from 125 to 190 (P < .001) prescriptions. Patient medication belonging to no gene-drug interaction significantly increased from 46.4% to 87.4% (P < .001), medications belonging to moderate and significant gene-drug interaction decreased from 32.8% to 7.9% (P < .001) and 11.2% to 2.1% (P = .012), respectively. 88.5% of patients' psychotropic medication treatment after PGx testing was consistent with the PGx test report recommendations. The PGx test lengths of time analysis indicated that patient follow-up exceeded the standard time set by guidelines at multiple steps in the test process. There are multiple opportunities for pharmacists to become involved in the PGx testing process to improve patient care.
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BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a significant epidemiological problem with rising prevalence. Due to limited literature, the objective of this study is to examine the association between polypharmacy and health-related quality of life (QoL) in NAFLD adult patients. METHODS: A retrospective observational study design was conducted to analyze health data collected by Steatohepatitis Clinical Research Network (NASH CRN). Patients were classified as receiving a polypharmacy therapy with five or more medications in their first screening visit. QoL was measured using the Short Form 36 (SF-36) instrument. Each patient self-reported the SF-36 form during the screening visit was compared between polypharmacy and non-polypharmacy groups using Wilcoxon Rank Sum test. Multivariable generalized linear models and multinomial logistic regression were performed to examine each predictor and its effect on QoL. RESULTS: Data included 1067 NAFLD adult patients; 834 patients used polypharmacy. The mean age was 48.64 years, and most patients were female (62%). Comparing NAFLD patients without steatohepatitis, borderline NASH, and definite NASH, the non-polypharmacy group had a significantly higher QoL than the polypharmacy group in Physical Component Summary (PCS) (86.25 vs 66.88, 85 vs 67.5, and 79.375 vs 63.12, respectively, all p < 0.01) and Mental Component Summary (MCS) (83.5 vs 73.38, 78.75 vs 67.62, and 78.75 vs 70.65, respectively, all p < 0.01). DISCUSSION AND CONCLUSION: Adults with NAFLD and polypharmacy have lower QoL than adults with NAFLD and non-polypharmacy. Number of medications had a significant negative impact on PCS, MCS, and all SF-36 domains except mental health, role physical limitation and role emotional limitation domains. Other factors that affect QoL negatively in NAFLD adult patients are female gender, obesity, diabetes, depression, and unemployment. Higher income had favorable effect on QoL.
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Diabetes Mellitus , Hepatopatia Gordurosa não Alcoólica , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade/epidemiologia , Qualidade de Vida/psicologia , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: This study evaluates complications and reconstructive failure rates in implant-based reconstruction with radiotherapy. BACKGROUND: Postmastectomy radiotherapy may adversely affect breast reconstructive outcomes. However, the comparative effect of radiotherapy on direct-to-implant versus tissue expander-implant reconstruction has not been examined. METHODS: Single institution retrospective review was performed and patients were followed 2 to 10âyears. RESULTS: Of 1566 patients, 265 patients received radiation (149 immediate implants and 116 tissue expanders). Demographics were similar except more smokers in the expander group (7.7% vs 1.3%; P = 0.012). Patients who received radiation with an expander in place had overall more complications (32.8% vs 11.4%; P < 0.001), skin necrosis (10.3% vs 4.0%; P = 0.043), wound breakdown (9.5% vs 2.7%; P = 0.029), and infections (16.4% vs 4.03%; P = 0.001) leading to a higher rate of explantation (16.4% vs 4.0%; P < 0.001). A radiation boost likewise predicted complications [odds ratio (OR) 2.199, 95% confidence interval (CI) 1.154-4.188, P = 0.017]. When comparing reconstructive outcomes, radiated expanders had a higher failure rate (21.6% vs 11.4%; P = 0.025). Revision for capsular contracture was similar between the 2 cohorts (11.4% vs 11.2%; P = 0.959) as were revision rates for contour asymmetry and breast asymmetry. In our multivariable logistic regression analysis, radiation to the expander had a higher risk of reconstruction failure than radiation to the permanent implant (OR 2.020, 95% CI 1.010-4.037, P = 0.047). CONCLUSION: Most patients had successful implant-based reconstructions after mastectomy and radiotherapy. Our study showed radiotherapy after direct-to-implant breast reconstruction had a lower rate of complications and reconstructive failure compared to tissue expander-implant reconstruction.
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Implantes de Mama , Neoplasias da Mama/radioterapia , Mamoplastia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Dispositivos para Expansão de TecidosRESUMO
BACKGROUND: This study aimed to evaluate the association of asymptomatic pyuria before ureterorenoscopic lithotripsy (URSL) with postoperative febrile urinary tract infection (UTI). METHODS: This observational case-control study identified the patients undergoing URSL for ureteral stones between May 2011 and October 2015. The included patients were classified into two groups: the asymptomatic pyuria group (6-50 white blood cells [WBCs]/high-power field [HPF]) and the non-pyuria group (≤ 5 WBCs/HPF). All data were collected by reviewing medical records. Postoperative outcomes were collected in terms of febrile UTI, emergency visits, and stone-free rate. RESULTS: A total of 232 patients were included, 101 in the pyuria group, 131 in the non-pyuria group. Two (0.9%) patients developed febrile UTI after URSL and 12 (5.2%) patients visited emergency department for URSL-related symptoms. The overall stone-free rate was 90.9%. There was no significant difference between the pyuria and non-pyuria groups regarding febrile UTI, emergency visits, and stone-free rate. Multivariate analysis revealed that pyuria was neither significantly associated with postoperative febrile UTI (OR = 1.03, 95% CI = 0.06-18.10, P = 0.98), nor with emergency visits (OR = 0.48, 95% CI = 0.13-1.85, P = 0.29). CONCLUSIONS: Compared to the patients with sterile urine prior to URSL, those with asymptomatic pyuria were not prone to develop febrile UTI after URSL.
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Litotripsia/efeitos adversos , Período Pré-Operatório , Piúria/diagnóstico , Cálculos Ureterais/cirurgia , Ureteroscopia/efeitos adversos , Infecções Urinárias/etiologia , Adulto , Doenças Assintomáticas , Estudos de Casos e Controles , Feminino , Febre/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Fatores de RiscoRESUMO
The aims were to develop an integrated electronic medication reconciliation (ieMR) platform, evaluate its effects on preventing potential duplicated medications, analyze the distribution of the potential duplicated medications by the Anatomical Therapeutic and Chemical (ATC) code for all inpatients, and determine the rate of 30-day medication-related hospital revisits for a geriatric unit. The study was conducted in a tertiary medical center in Taiwan and involved a retrospective quasi pre-intervention (July 1-November 30, 2015) and post-intervention (October 1-December 31, 2016) study design. A multidisciplinary team developed the ieMR platform covering the process from admission to discharge. The ieMR platform included six modules of an enhanced computer physician order entry system (eCPOE), Pharmaceutical-care, Holistic Care, Bedside Display, Personalized Best Possible Medication Discharge Plan, and Pharmaceutical Care Registration System. The ieMR platform prevented the number of potential duplicated medications from pre (25,196 medications, 2.3%) to post (23,413 medications, 3.8%) phases (OR 1.71, 95% CI, 1.68-1.74; p < .001). The most common potential duplicated medications classified by the ATC codes were cardiovascular system (28.4%), alimentary tract and metabolism (26.4%), and nervous system (14.9%), and by chemical substances were sennoside (12.5%), amlodipine (7.5%), and alprazolam (7.4%). The rate of medication-related 30-day hospital revisits for the geriatric unit was significantly decreased in post-intervention compared with that in pre-intervention (OR = 0.12; 95% CI, 0.03-0.53; p < .01). This study indicated that the ieMR platform significantly prevented the number of potential duplicated medications for inpatients and reduced the rate of 30-day medication-related hospital revisits for the patients on the geriatric unit.
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Continuidade da Assistência ao Paciente/organização & administração , Erros de Medicação/prevenção & controle , Reconciliação de Medicamentos/organização & administração , Equipe de Assistência ao Paciente/organização & administração , Preparações Farmacêuticas/normas , Sistemas de Registro de Ordens Médicas/organização & administração , Sistemas Computadorizados de Registros Médicos/organização & administração , Serviço de Farmácia Hospitalar/organização & administração , Garantia da Qualidade dos Cuidados de Saúde , Estudos Retrospectivos , TaiwanRESUMO
The clinical guidelines for interstitial cystitis and related symptomatic conditions were revised by updating our previous guidelines. The current guidelines define interstitial cystitis/bladder pain syndrome as a condition with chronic pelvic pain, pressure or discomfort perceived to be related to the urinary bladder accompanied by other urinary symptoms, such as persistent urge to void or urinary frequency in the absence of confusable diseases. The characteristic symptom complex is collectively referred as hypersensitive bladder symptoms. Interstitial cystitis/bladder pain syndrome is divided into Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis and bladder pain syndrome represent interstitial cystitis/bladder pain syndrome with Hunner lesions and interstitial cystitis/bladder pain syndrome without Hunner lesions, respectively. So-called non-Hunner-type interstitial cystitis featured by glomerulations or bladder bleeding after distension is included in bladder pain syndrome. The symptoms are virtually indistinguishable between Hunner-type interstitial cystitis and bladder pain syndrome; however, Hunner-type interstitial cystitis and bladder pain syndrome should be considered as a separate entity of disorder. Histopathology totally differs between Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis is associated with severe inflammation of the urinary bladder accompanied by lymphoplasmacytic infiltration and urothelial denudation, whereas bladder pain syndrome shows little pathological changes in the bladder. Pathophysiology would also differ between Hunner-type interstitial cystitis and bladder pain syndrome, involving interaction of multiple factors, such as inflammation, autoimmunity, infection, exogenous substances, urothelial dysfunction, neural hyperactivity and extrabladder disorders. The patients should be treated differently based on the diagnosis of Hunner-type interstitial cystitis or bladder pain syndrome, which requires cystoscopy to determine the presence or absence Hunner lesions. Clinical studies are to be designed to analyze outcomes separately for Hunner-type interstitial cystitis and bladder pain syndrome.
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Cistite Intersticial , Cistite Intersticial/diagnóstico , Cistoscopia , Humanos , Dor Pélvica/diagnóstico , Dor Pélvica/etiologia , UrotélioRESUMO
The physiological state of a cell is governed by a multitude of processes and can be described by a combination of mechanical, spatial and temporal properties. Quantifying cell dynamics at multiple scales is essential for comprehensive studies of cellular function, and remains a challenge for traditional end-point assays. We introduce an efficient, non-invasive computational tool that takes time-lapse images as input to automatically detect, segment and analyze unlabeled live cells; the program then outputs kinematic cellular shape and migration parameters, while simultaneously measuring cellular stiffness and viscosity. We demonstrate the capabilities of the program by testing it on human mesenchymal stem cells (huMSCs) induced to differentiate towards the osteoblastic (huOB) lineage, and T-lymphocyte cells (T cells) of naïve and stimulated phenotypes. The program detected relative cellular stiffness differences in huMSCs and huOBs that were comparable to those obtained with studies that utilize atomic force microscopy; it further distinguished naïve from stimulated T cells, based on characteristics necessary to invoke an immune response. In summary, we introduce an integrated tool to decipher spatiotemporal and intracellular dynamics of cells, providing a new and alternative approach for cell characterization.
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Bases de Dados como Assunto , Imageamento Tridimensional , Análise de Célula Única/métodos , Adulto , Algoritmos , Animais , Automação , Fenômenos Biomecânicos/efeitos dos fármacos , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Elasticidade , Humanos , Ionomicina/farmacologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Fenótipo , Acetato de Tetradecanoilforbol/farmacologia , Fatores de Tempo , ViscosidadeRESUMO
Cultural responsiveness is a key aspect of the quality of organized activities, yet has rarely been examined. Based on developmental theories and a theoretical framework for culturally responsive activities, the current study investigated the prevalence and correlates of two ethnic cultural features (i.e., ethnic cultural content & ethnic cultural respect) in organized activities. Using data from 154 Latino adolescents (Mage = 12.36, SD = .53; 59% Female) and parents, we examined associations between adolescent perceptions of both ethnic cultural features and their activity experiences; and associations between parent perceptions of both ethnic cultural features and parental involvement in the activity. Latino adolescents and parents in general perceived lower than average ethnic cultural content and moderate to high ethnic cultural respect in the reported activity. Both adolescents and parents were more likely to perceive ethnic cultural content and respect in activities where Latino youth were the numerical ethnic majority than in activities where Latino youth were the numerical ethnic minority. Latino adolescents' perceptions of ethnic cultural respect were associated with more positive activity experiences, whereas their perceptions of ethnic cultural content were associated with more negative feelings. Latino parents' perceptions of ethnic cultural content predicted higher involvement. To design culturally responsive activities, ethnic cultural features should be incorporated in a thoughtful, meaningful way that reflects both adolescents' and parents' perspectives.
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Comportamento do Adolescente/etnologia , Características Culturais , Atividades de Lazer/psicologia , Relações Pais-Filho/etnologia , Participação Social/psicologia , Adolescente , Criança , Etnicidade , Feminino , Hispânico ou Latino/psicologia , Humanos , Masculino , Pais/psicologiaRESUMO
AIMS: To investigate the pathogenic role of activation of the mammalian target of the rapamycin (mTOR) in the ketamine induced microvascular injury. METHODS: Twenty-three patients with ketamine-induced cystitis (KC) and 16 control volunteers were recruited. Bladder tissues were obtained from both groups by cystoscopic biopsies. Phospho-S6 ribosomal protein (p-S6RP), an end product of the mTOR pathway, was stained in the urinary bladder from both groups. Endothelial cells of the urinary bladder (HBdMECs) were examined to investigate the in vitro activation of the mTOR pathway and the co-expression of the endothelial marker (cluster of differentiation 31 [CD31]) and the mesenchymal marker (fibroblast-specific protein 1 [FSP-1]). RESULTS: Expression of p-S6RP increased significantly after ketamine exposure, especially in the vesical microvessels of KC patients. In HBdMECs treated with 100 µM Ketamine, time-dependent activation of the mTOR pathway occurred, with significantly increased levels of the phosphorylated forms of mTOR at 30 min and of S6RP and p70S6 kinase (p70S6K) at 6 h. The increased level of p-S6RP returned to baseline within 2 days after ketamine exposure. The co-expression of CD31 and FSP-1 implied that EndMT was present in HBdMECs at 7 days after ketamine treatment, while TGF-ß1 facilitated significant up-regulation of FSP-1 at 1 day after treatment. Furthermore, when the mTOR inhibitor rapamycin was administered with ketamine to the HBdMECs, the expression of FSP-1 decreased significantly. CONCLUSIONS: Ketamine induces activation of the mTOR pathway and subsequent mesenchymal phenotypic expression (FSP1) in HBdMECs.
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Cistite/metabolismo , Ketamina/efeitos adversos , Microvasos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Bexiga Urinária/metabolismo , Adulto , Cistite/induzido quimicamente , Feminino , Humanos , Ketamina/administração & dosagem , Masculino , Microvasos/efeitos dos fármacos , Pessoa de Meia-Idade , Fosforilação/efeitos dos fármacos , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Bexiga Urinária/efeitos dos fármacos , Adulto JovemRESUMO
AIMS: Terms used in the field of chronic pelvic pain (CPP) are poorly defined and often confusing. An International Continence Society (ICS) Standard for Terminology in chronic pelvic pain syndromes (CPPS) has been developed with the aim of improving diagnosis and treatment of patients affected by chronic pelvic pain syndromes. The standard aims to facilitate research, enhance therapy development and support healthcare delivery, for healthcare providers, and patients. This document looks at the whole person and all the domains (organ systems) in a systematic way. METHODS: A dedicated working group (WG) was instituted by the ICS Standardisation Steering Committee according to published procedures. The WG extracted information from existing relevant guidelines, consensus documents, and scientific publications. Medline and other databases were searched in relation to each chronic pelvic pain domain from 1980 to 2014. Existing ICS Standards for terminology were utilized where appropriate to ensure transparency, accessibility, flexibility, and evolution. Consensus was based on majority agreement. RESULTS: The multidisciplinary CPPS Standard reports updated consensus terminology in nine domains; lower urinary tract, female genital, male genital, gastrointestinal, musculoskeletal, neurological aspects, psychological aspects, sexual aspects, and comorbidities. Each is described in terms of symptoms, signs and further evaluation. CONCLUSION: The document presents preferred terms and definitions for symptoms, signs, and evaluation (diagnostic work-up) of female and male patients with chronic pelvic pain syndromes, serving as a platform for ongoing development in this field. Neurourol. Urodynam. 36:984-1008, 2017. © 2016 Wiley Periodicals, Inc.
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Dor Pélvica/classificação , Dor Pélvica/etiologia , Dor Crônica , Feminino , Humanos , Masculino , Dor Pélvica/diagnóstico , Terminologia como AssuntoRESUMO
Background Earlier, digit viability judged the success of digital replantation. Now, utility health-related quality of life (HRQOL) measures can better assess the impact of digital replantation. Methods Overall, 264 digital injury patients were sent a regimen of utility measures: Disabilities of the Arm, Shoulder and Hand (DASH) score, European Quality of Life 5 Dimensions, visual analog scale (VAS), time trade-off (TTO), and standard gamble (SG). Overall, 51 patients responded completely to all of these-36 replantation patients and 15 revision amputation patients. The utility results of these patients were stratified between replantation versus revision amputation; dominant hand replantation versus nondominant hand replantation; and dominant hand revision amputation versus nondominant hand revision amputation. Results The mean VAS score of replant (0.84) and revision amputation (0.75) groups was significantly different (p = 0.05). The mean DASH score of dominant hand replantations (29.72) and nondominant hand replantations (17.97) was significantly different (p = 0.027). The dominant hand revision amputation had higher anxiety levels in comparison to nondominant hand revision amputation (p = 0.027). Patients with two or more digits replanted showed a significant decrease in VAS, TTO, and SG scores in comparison to patients who only had one digit replanted (p = 0.009, 0.001, and 0.001, respectively). Conclusions This study suggests that HRQOL can offer better indices for outcomes of digital replantation. This shows some specific replantation cohorts have a significantly better quality of life when compared with their specific correlating revision amputation cohort. These findings can be employed to further refine indications and contraindications to replantation and help predict the quality of life outcomes.
Assuntos
Amputação Cirúrgica , Traumatismos dos Dedos/psicologia , Traumatismos dos Dedos/cirurgia , Satisfação do Paciente/estatística & dados numéricos , Qualidade de Vida , Recuperação de Função Fisiológica/fisiologia , Reoperação/psicologia , Reimplante , Adulto , Idoso , Amputação Cirúrgica/psicologia , Amputação Cirúrgica/reabilitação , Avaliação da Deficiência , Feminino , Traumatismos dos Dedos/fisiopatologia , Força da Mão/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Ocupações , Quebeque , Reoperação/reabilitação , Reimplante/psicologia , Reimplante/reabilitação , Estudos Retrospectivos , AutoeficáciaRESUMO
BACKGROUND: Surgery is the potentially curative treatment for retroperitoneal sarcoma (RS), but complete resectability is frequently a challenge. This study aimed to characterize the clinical features, prognostic factors and treatment outcomes. METHODS: A cohort of 144 patients with RS was surveyed retrospectively from January 1st, 2000 to July 30th, 2011. The prognostic influence of clinicopathological characteristics as well as treatments on local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS), were examined by univariate and multivariate analyses. A histology-specific nomogram developed by Gronchi et al was used for validation. RESULTS: Liposarcoma, leiomyosarcoma, and malignant peripheral sheath tumor (MPNST) were the most common histologies (70%). Multivariate analysis revealed FNCLCC tumor grade was the most significant prognostic factor for OS (P = 0.001) and DMFS (P < 0.001) and complete resection was the only significant prognostic factor for LRFS (P = 0.043). Incomplete resection of grade 3 tumor was significantly associated with a worse OS. Despite some differences in characteristics between our patients and Gronchi's cohort, external validation of Gronchi's nomogram demonstrated excellent concordance in predicting survival. CONCLUSIONS: Our study demonstrated tumor grade and surgical margins had significant prognostic influence and the Gronchi's nomogram has an excellent applicability in predicting survival of STS patients. J. Surg. Oncol. 2016;113:355-360. © 2016 Wiley Periodicals, Inc.