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2.
PLoS One ; 15(5): e0233527, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469921

RESUMO

The prevalence of urinary incontinence in Duchenne and Becker muscular dystrophy (D/BMD) is reported to be between 15-29%, this however includes ages across the lifespan, and with no description of impact on daily life. The present study, aimed to determine the prevalence of urinary incontinence in men with D/BMD, and to identify which aspects of daily life were impacted by urinary incontinence. Twenty-seven adult males, 11 with BMD and 16 with DMD, aged 20-57 years, volunteered to participate in this study. Six questionnaires were completed to provide an overview of participant mobility, urinary incontinence and distress caused by urinary incontinence. These included: The Barthel index of disability, International Consultation on Incontinence Questionnaire-Urinary Incontinence Form, Incontinence Impact Questionnaire Short Form, The Urogenital Distress Inventory, and the Brooke and Vignos scale. The prevalence of urinary incontinence within the present men with D/BMD was 37%, assessed as urine leakage of once a week or more. Those with urinary incontinence all reported only a "small amount" of urine leakage, with urinary incontinence frequency of once a week in 5/10 participants, two or three times a week in 2/10 participants, and once a day in 3/10 participants. Of those with urinary incontinence 8/10 experienced some impact on their daily life from urine leakage including travel (4/10), social aspects (5/10), and emotional aspects (8/10). All participants with urinary incontinence were bothered by some aspect, including urine leakage (9/10), and frequent urination (4/10). In conclusion, 37% of the present men with D/BMD experience urinary incontinence on a weekly or daily basis and negatively impacted aspects of life related to travel, social and emotional wellbeing. Urine leakage, and frequent urination should be considered a meaningful problem by care providers, and discussed openly with those with D/BMD.

4.
J Gastrointest Surg ; 24(6): 1411-1416, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32300963

RESUMO

INTRODUCTION: Laparoscopic Heller Myotomy is the most effective treatment of achalasia. We examined the durability of symptomatic relief, with and without fundoplication. METHODS: A single institution database between 1995 and 2017 was reviewed. Achalasia symptom severity was assessed by Eckardt scores (ES) obtained at 3-time points via patient questionnaire. Primary outcome was treatment success defined as ES of < 3. RESULTS: Completed surveys were returned by 130 patients (median follow-up of 6.6 years). A partial fundoplication was performed in 86%. At both 1-year and late follow-up, patients reported a significant improvement in ES compared to baseline (p < 0.05). Of those followed for ≥ 10 years (n = 44), 82% reported ES < 3 at 1-year (p < 0.001), and 78% at last follow-up (p < .001). Of patients who reported treatment success 1-year postoperatively (103/130), 85% continued to report symptomatic relief at last follow-up. Five-year cohort analysis did not show deterioration of dysphagia relief over time. The presence or absence of fundoplication had no impact on long-term outcome (p > 0.05). CONCLUSIONS: LHM provides immediate and durable symptomatic relief, with very few patients requiring further therapeutic intervention. Fundoplication does not appear to influence the durability of symptom relief. Treatment success at 1-year is predictive of long-lasting symptomatic relief.

5.
Sci Rep ; 10(1): 2913, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32076017

RESUMO

The prevalence of sarcopenia depends on the definition used. There are, however, consistent sarcopenic characteristics, including a low muscle mass and muscle strength. Few studies have investigated the relationship between sarcopenia and genotype. A cross-sectional study was conducted with 307 community-dwelling ≥60-year-old women in South Cheshire, UK. Handgrip strength was assessed with a handgrip dynamometer and skeletal muscle mass was estimated using bioelectrical impedance. DNA was extracted from saliva (∼38%) or blood (∼62%) and 24 single-nucleotide polymorphisms (SNPs) were genotyped. Three established sarcopenia definitions - %Skeletal Muscle Mass (%SMM), Skeletal Muscle Mass Index (SMI) and European Working Group on Sarcopenia in Older People (EWGSOP) - were used to assess sarcopenia prevalence. Binary logistic regression with age as covariate was used to identify SNPs associated with sarcopenia. The prevalence of sarcopenia was: %SMM 14.7%, SMI 60.6% and EWGSOP 1.3%. Four SNPs were associated with the %SMM and SMI definitions of sarcopenia; FTO rs9939609, ESR1 rs4870044, NOS3 rs1799983 and TRHR rs7832552. The first three were associated with the %SMM definition, and TRHR rs7832552 with the SMI definition, but none were common to both sarcopenia definitions. The gene variants associated with sarcopenia may help proper counselling and interventions to prevent individuals from developing sarcopenia.

7.
J Clin Psychol ; 76(5): 841-851, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31909837

RESUMO

Since September 11, 2001, the United States has engaged in an extended period of military conflict, resulting in 4.1 million men and women serving in support of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn. Whereas not all servicemembers experience mental health issues, many have experienced difficulties with readjusting to the civilian world, often requiring mental health services both inside and outside of the Department of Veterans Affairs. Issues related to stigma and military culture contribute to barriers not only for veterans seeking treatment but for clinicians providing services who may lack experience with military culture. This article provides a framework to use military concepts in clinical sessions to further therapeutic engagement with the military/veteran client.

8.
J Gastrointest Surg ; 24(5): 983-990, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31144192

RESUMO

INTRODUCTION: The clinical impact of a positive radial margin after esophagectomy for cancer has not been clearly  identified. The goal of this study was to identify risk factors for a positive radial margin and determine the impact on recurrence and survival. METHODS: Retrospective review of 196 patients with pathological T3 N0-3 esophageal adenocarcinoma undergoing esophagectomy between 2002 and 2017. Mortality data was extracted from Electronic Medical Records and Social Security Death Index. RESULTS: Mean age was 63.7 ± 11.4 years, and there were 166 (84.7%) men. Neoadjuvant therapy was given in 141(71.9%) patients. We identified 29(14.8%) patients with a positive radial margin. Factors significantly associated with a positive radial margin include not receiving neoadjuvant therapy and presence of lymphatic, vascular, or perineural invasion. Overall, there were 94(48%) recurrences during a mean follow-up of 24.7 months. Involvement of the radial margin was not significantly associated with recurrence-free survival (HR 1.24, CI 95% 0.73-2.12, p = 0.425). Overall survival for the entire cohort was 41.6% and 28.9% at 3 and 5 years, respectively. Involvement of the radial margin did not have a significant impact on overall survival (HR 1.23, CI 95% 0.68-2.22, p = 0.493). CONCLUSIONS: The likelihood of encountering a positive margin is associated with lack of neoadjuvant treatment and the presence of lymphatic, vascular, or perineural invasion in the esophagectomy specimen. An involved radial margin after esophagectomy for locally advanced cancer was not associated with tumor recurrence or overall survival in our cohort, and other factors such as lymph node involvement are stronger in determining outcome.

9.
Gait Posture ; 75: 149-154, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683185

RESUMO

BACKGROUND: Gastrocnemius medialis (GM) and lateralis (GL) act at the ankle complex in the sagittal and frontal planes and there is evidence that their actions can be somewhat uncoupled from each other. Some independence of GM and GL from each other could be advantageous, e.g. to stabilise the ankle complex in unstable walking conditions. Given the compartmentalised structure of the Achilles tendon, the sub-tendons of GM and GL may exhibit different elongation during plantarflexion contractions, particularly with the foot in different frontal plane positions. RESEARCH QUESTIONS: METHODS: Sub-tendon elongation was determined from 18 participants during ramped isometric plantarflexion contractions to 70% of their maximum voluntary contraction (MVC) level with the foot in neutral, inversion and eversion. One-dimensional statistical parametric mapping was applied to determine elongation differences. RESULTS: Elongation within a sub-tendon did not differ in the three foot positions. Elongation was similar between both sub-tendons at very low contraction levels, but GM sub-tendon elongation exceeded GL sub-tendon displacement significantly from 30% MVC. The elongation differences between the sub-tendons were not affected by foot position. SIGNIFICANCE: Greater GM sub-tendon elongation is likely caused by the greater force production capability of GM but may also indicate that the sub-tendons of GM and GL have different mechanical properties, which is currently unknown. Elongation differences were contraction level dependent suggesting that contributions of GM and GL to plantarflexion torque may also be contraction level dependent.


Assuntos
Articulação do Tornozelo/fisiologia , Pé/fisiologia , Músculo Esquelético/fisiologia , Tendões/fisiologia , Tendão do Calcâneo/fisiologia , Adulto , Feminino , Humanos , Contração Isométrica/fisiologia , Masculino , Pessoa de Meia-Idade , Torque
10.
Front Neurol ; 10: 1216, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31803134

RESUMO

Background: The inclusion of resistance training in the treatment and management of muscular dystrophy has previously been discouraged, based on mainly anecdotal evidence. There remains a lack of experimental investigation into resistance training in individuals with muscular dystrophy. The aim of the current study was therefore, to determine the effect of a 12-week resistance training programme on muscle strength and functional tasks in ambulatory adults with muscular dystrophy. Methods: Seventeen ambulatory adults with muscular dystrophy (Facioscapulohumeral muscular dystrophy: n = 6, Limb-Girdle muscular dystrophy: n = 6, Becker muscular dystrophy: n = 5) were recruited for this study. Participants attended three testing sessions: one session at baseline, one session after a 12-week control period and one session after a 12-week resistance training period. Each testing session consisted of measurements of isometric knee extensor and knee flexor maximum voluntary contraction (MVC) torque (Cybex dynamometer). Participants also completed a timed sit-to-stand, a four steps-stair ascent, and a four steps-stair decent. The 12-week resistance training period consisted of two supervised sessions a week. Each training session included a 5-min warm-up, a step-up exercise, free-standing or assisted squats, knee flexion and knee extension exercises, and an additional 6 single-joint exercises specific to each individual's needs. Results: Knee flexor MVC torque increased by 13% after the 12-week resistance training programme (p < 0.05), with no change over the control period. Knee extensor MVC torque did not significantly change after the training programme or the control period. Time taken to complete sit-to-stand, stair ascent and stair descent all decreased (improved) following the 12-week training programme (p < 0.05). Conclusions: A twice-a-week, 12-week, resistance training programme resulted in increased knee flexion strength and improvements in functional tasks in ambulatory adults with muscular dystrophy. This provides support for the inclusion of resistance training in the treatment programmes for these forms of muscular dystrophy.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31679701

RESUMO

OBJECTIVES: The study objectives were to evaluate the immediate, short-, and medium-term efficacy and safety of pulmonary artery branch sealing using an ultrasonic vessel-sealing device in minimally invasive anatomic lung resection. METHODS: This study consists of a prospective, phase 2, multicenter, international clinical trial (clinicaltrials.gov: NCT02719717) that enrolled patients planned for video-assisted thoracoscopic surgery/robotic anatomic lung resection in 7 centers (United States, Canada, United Kingdom). Pulmonary artery branches of 7 mm or less were sealed and divided with an ultrasonic energy vessel-sealing device. The remainder of the lobectomy was performed according to surgeon preference. Intraoperative, in-hospital, and 30-day postoperative bleeding and complications were prospectively recorded. RESULTS: A total of 150 patients with a minimum of 1 pulmonary artery branch sealed with an ultrasonic vessel-sealing device were prospectively enrolled in the trial. Resections included 139 lobectomies and 11 segmentectomies. A total of 424 pulmonary artery branches were divided: 239 with the ultrasonic vessel-sealing device, 181 with endostaplers, and 4 with endoscopic clips. The mean and median pulmonary artery diameters were 4.7 mm/5.0 mm, 10.3 mm/10.0 mm, and 6.5 mm/6.5 mm for each method, respectively. Three of the pulmonary artery branches divided with the ultrasonic vessel-sealing device (1.3%) and 4 pulmonary artery branches divided with endostaplers (2.2%) bled intraoperatively. Among the patients with seal failures, 1 patient required conversion to thoracotomy. There was no postoperative bleeding from divided pulmonary artery branches with either sealing method. There was no mortality at 30 days. CONCLUSIONS: Pulmonary artery branch sealing with ultrasonic energy during video-assisted thoracoscopic surgery lobectomy is safe for vessels 7 mm or less. The use of an ultrasonic device is a reasonable sealing method for pulmonary artery branches 7 mm or less.

12.
PLoS One ; 14(10): e0224223, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31644560

RESUMO

BACKGROUND: It has been advocated that older adults should concomitantly spend less time in sedentary behaviour (SB), and engage in sufficient physical activity (PA), to reduce their risk of cardio-metabolic diseases. However, it is not clear what intensity of PA must be done to offset SB engagement. AIM: Model how cardio-metabolic profiles could change if older adults replaced an hour per day (hr·day-1) of a physical behaviour intensity with 1 hr·day-1 of another physical behaviour of a different intensity. METHODS: Older adults (n = 93, 60-89 years old, 55% female) wore a thigh-mounted triaxial accelerometer for seven consecutive free-living days to estimate mean daily hourly engagement in SB, Standing, Light Intensity PA (LIPA), sporadic moderate to vigorous physical activity (sMVPA, bouts <10 continuous minutes), and 10-minute MVPA (10MVPA, bouts ≥10 continuous minutes. Fasting whole blood concentration of plasma glucose, triglyceride, total cholesterol, and glycated haemoglobin (%), along with serum concentration of lipoprotein lipase (LPL), interleukin-6 (IL-6), and procollagen III N-terminal propeptide (PIIINP) were measured. RESULTS: Isotemporal Substitution, with covariate adjustment, suggested that: total cholesterol concentration could theoretically decrease when 1 hr·day-1 of SB is replaced with Standing, when 1 hr.day-1 of LIPA is replaced with Standing, and when 1 hr·day-1 of sMVPA is replaced with Standing. Triglyceride concentration theoretically decreased when 1 hr·day-1 of SB, Standing, LIPA, or sMVPA is replaced with 10MVPA. Triglyceride concentration theoretically increases when 1 hr·day-1 of 10MVPA is replaced with SB, Standing, or LIPA. No associations with time reallocation appears to exist for LPL, HbA1c, IL-6, and PIIINP. CONCLUSION: The type of physical behaviour being replaced could be crucial for total cholesterol maintenance. Engagement in 10MVPA could be necessary to improve triglyceride concentration.


Assuntos
Doenças Cardiovasculares/diagnóstico , Exercício Físico , Doenças Metabólicas/diagnóstico , Metaboloma , Comportamento Sedentário , Acelerometria , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Doenças Cardiovasculares/psicologia , Feminino , Humanos , Masculino , Doenças Metabólicas/psicologia , Pessoa de Meia-Idade , Prognóstico
13.
J Thorac Dis ; 11(Suppl 15): S1954-S1956, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31632796
14.
Musculoskelet Sci Pract ; 44: 102038, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31536882

RESUMO

BACKGROUND: The dynamic disc model refers to the ability of a spinal disc's position to be manipulated by body postures and movements. Research on lumbar discs has indicated movement of the anterior and posterior disc that correlates with posture of the spine. The aim of this study was to assess whether, despite its structural differences, the cervical disc responds to flexed and extended postures in a similar fashion to the lumbar disc. METHOD: A repeated measures study. Twenty five asymptomatic participants (age: 33.7 ±â€¯9.1 years) volunteered. Scans were performed in supine using an Esaote 0.2T magnetic resonance imaging scanner. Participants lay with their cervical spine initially placed in neutral, followed by flexion and finally extension. The position of the posterior disc nucleus pulposus at C5-6 and C6-7 was measured against a vertical line connecting the posterior vertebral bodies above and below each disc. RESULTS: Changes in cervical spine position were associated with significant changes in posterior disc nucleus pulposus position at both C5-6 and C6-7 (p < 0.01 for both). Post hoc testing showed a significant difference in posterior disc nucleus pulposus position at C5-6 between flexion and extension (p = 0.02). There was similarly a significant change at C6-7 between neutral and flexion (p = 0.001), and between flexion and extension (p = 0.02). CONCLUSIONS: These results indicate that the cervical posterior nucleus pulposus is affected by spinal loading, consistent with the concept of the dynamic disc model.

15.
J Cachexia Sarcopenia Muscle ; 10(6): 1295-1306, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31508907

RESUMO

BACKGROUND: Sarcopenia is characterized by progressive decreases in muscle mass, muscle strength, and muscle function with ageing. Although many studies have investigated the mechanisms of sarcopenia, its connection with epigenetic factors, such as DNA methylation, still remains poorly understood. The aim of this study was to explore sarcopenia-related DNA methylation differences in blood samples between age-matched sarcopenic and non-sarcopenic older women. METHODS: A sarcopenic group (n = 24) was identified and selected from a set of 247 older Caucasian women (aged 65-80 years) based on cut-off points of skeletal muscle index at 6.75 kg/m2 and grip strength at 26 kg (the lower quintile of grip strength in the set). A non-sarcopenic group (n = 24) was created with a similar age distribution as that of the sarcopenic group. DNA methylation patterns of whole blood samples from both groups were analysed using Infinium MethylationEPIC BeadChip arrays. Differentially methylated cytosin-phosphate-guanine sites (dmCpGs) were identified at a P value threshold of 0.01 by comparing methylation levels between the sarcopenic and non-sarcopenic groups at each CpG site. dmCpG-related genes were annotated based on Homo sapiens hg19 genome build. The functions of these genes were further examined by GO and KEGG pathway enrichment analysis. RESULTS: The global methylation level of all analysed CpG sites (n = 788 074) showed no significant difference between the sarcopenic and non-sarcopenic groups (0.812), while the average methylation level of dmCpGs (n = 6258) was significantly lower in the sarcopenic group (0.004). The sarcopenic group had significantly higher methylation levels in TSS200 (the region from transcription start site to 200 nucleotides upstream of the site) and lower methylation levels in gene body and 3'UTR regions. In respect of CpG regions, CpG islands in promoters and some intragenic regions showed greater levels of methylation in the sarcopenic group. dmCpG-related KEGG pathways were mainly associated with muscle function, actin cytoskeleton regulation, and energy metabolism. Seven genes (HSPB1, PBX4, CNKSR3, ORMDL3, MIR10A, ZNF619, and CRADD) were found with the same methylation direction as previous studies of blood sample methylation during ageing. Fifty-four genes were shared with previous studies of resistance training. CONCLUSIONS: Our results improve understanding of epigenetic mechanisms of sarcopenia by identifying sarcopenia-related DNA methylation differences in blood samples of older women. These methylation differences suggest underlying alterations of gene expression and pathway function, which can partially explain sarcopenia-related muscular changes.

16.
Surg Endosc ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31388809

RESUMO

BACKGROUND: Approximately 3-6% of patients undergoing anti-reflux surgery require "redo" surgery for persistent gastroesophageal reflux disease (GERD). Further surgery for patients with two failed prior anti-reflux operations is controversial due to the morbidity of reoperation and poor outcomes. We examined our experience with surgical revision of patients with at least two failed anti-reflux operations. METHODS: Adults undergoing at least a second-time revision anti-reflux surgery between 1999 and 2017 were eligible. The primary outcomes were general and disease-specific quality-of-life (QoL) scores determined by Short-Form-36 (SF36) and GERD-Health-Related QoL (GERD-HRQL) instruments, respectively. Secondary outcomes included perioperative morbidity and mortality. RESULTS: Eighteen patients undergoing redo-redo surgery (13 with 2 prior operations, 5 with 3 prior operations) were followed for a median of 6 years [IQR 3, 12]. Sixteen patients (89%) underwent open revisions (14 thoracoabdominal, 2 laparotomy) and two patients had laparoscopic revisions. Indications for surgery included reflux (10 patients), regurgitation (5 patients), and dysphagia (3 patients). Intraoperative findings were mediastinal wrap herniation (9 patients), misplaced wrap (2 patients), mesh erosion (1 patient), or scarring/stricture (6 patients). Procedures performed included Collis gastroplasty + fundoplication (6 patients), redo fundoplication (5 patients), esophagogastrectomy (4 patients), and primary hiatal closure (3 patients). There were no deaths and 13/18 patients (72%) had no postoperative complications. Ten patients completed QoL surveys; 8 reported resolution of reflux, 6 reported resolution of regurgitation, while 4 remained on proton-pump inhibitors (PPI). Mean SF36 scores (± standard deviation) in the study cohort in the eight QoL domains were as follows: physical functioning (79.5 [± 19.9]), physical role limitations (52.5 [± 46.3]), emotional role limitations (83.3 [± 36.1]), vitality (60.0 [± 22.7]), emotional well-being (88.4 [± 8.7]), social functioning (75.2 [± 31.0]), pain (66.2 [± 30.9]), and general health (55.0 [± 39.0]). CONCLUSION: An open thoracoabdominal approach in appropriately selected patients needing third-time anti-reflux surgery carries low morbidity and provides excellent results as reflected in QoL scores.

17.
Health Qual Life Outcomes ; 17(1): 121, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307472

RESUMO

BACKGROUND: Muscle weakness is a defining characteristic of Muscular Dystrophy (MD); however, yet while speculated, objective measures of muscle weakness has not been reported in relation to quality of life in adults with MD. OBJECTIVES: 1) compare the self-reported QoL of adults with Duchenne MD (DMD), Beckers MD (BMD), Limb-Girdle MD (LGMD) and Fascioscapulohumeral MD (FSHD, and a non-MD (CTRL) group; 2) present and compare between groups measures of Impairment (Muscle Strength and Activities of Daily Living) and Perception (Fatigue, Pain and Self-Efficacy); and 3) identify associations between QoL domains and measures of Impairment and Perception (See above). METHODS: Seventy-Five males, including MD classifications DMD, BMD, LGMD, FSHD and CTRL, completed measures for QoL, Knee-Extension Maximal Voluntary Contraction (KEMVC), Fatigue, Pain, Self-Efficacy and Activities of Daily Living (ADL). RESULTS: QoL was lower across many domains in MD than CTRL. FSHD scored lower than DMD for mental wellbeing domains. KEMVC associated with Physical-Function domain for BMD. Pain, Self-Efficacy and ADLs associated with QoL domains, with Fatigue the most consistently associated. CONCLUSION: The present study identified differences between MD classifications within self-perceptions of mental-health. Muscle weakness is a defining feature of MD; however, it doesn't define QoL in adults with MD. A greater understanding of mental wellbeing, independence, and management of fatigue and pain, are required to improve QoL for adults with MD.


Assuntos
Atividades Cotidianas/psicologia , Força Muscular , Distrofia Muscular de Duchenne/psicologia , Qualidade de Vida , Adulto , Estudos Transversais , Fadiga/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular , Dor/psicologia , Autoeficácia , Autorrelato , Adulto Jovem
18.
Cancer Immunol Res ; 7(9): 1412-1425, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31337659

RESUMO

Adoptive T-cell therapy using high-affinity T-cell receptors (TCR) to target tumor antigens has potential for improving outcomes in high-grade serous ovarian cancer (HGSOC) patients. Ovarian tumors develop a hostile, multicomponent tumor microenvironment containing suppressive cells, inhibitory ligands, and soluble factors that facilitate evasion of antitumor immune responses. Developing and validating an immunocompetent mouse model of metastatic ovarian cancer that shares antigenic and immunosuppressive qualities of human disease would facilitate establishing effective T-cell therapies. We used deep transcriptome profiling and IHC analysis of human HGSOC tumors and disseminated mouse ID8VEGF tumors to compare immunologic features. We then evaluated the ability of CD8 T cells engineered to express a high-affinity TCR specific for mesothelin, an ovarian cancer antigen, to infiltrate advanced ID8VEGF murine ovarian tumors and control tumor growth. Human CD8 T cells engineered to target mesothelin were also evaluated for ability to kill HLA-A2+ HGSOC lines. IHC and gene-expression profiling revealed striking similarities between tumors of both species, including processing/presentation of a leading candidate target antigen, suppressive immune cell infiltration, and expression of molecules that inhibit T-cell function. Engineered T cells targeting mesothelin infiltrated mouse tumors but became progressively dysfunctional and failed to persist. Treatment with repeated doses of T cells maintained functional activity, significantly prolonging survival of mice harboring late-stage disease at treatment onset. Human CD8 T cells engineered to target mesothelin were tumoricidal for three HGSOC lines. Treatment with engineered T cells may have clinical applicability in patients with advanced-stage HGSOC.

19.
Thorac Surg Clin ; 29(3): 269-277, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31235295

RESUMO

Resident education in the operating room and surgical resident autonomy represent two enormous challenges within cardiothoracic (CT) training programs. The goal of surgical educators and CT trainees is to ensure the graduating resident's ability to safely operate independently at the completion of training. The field has come a long way from the notion of see one, do one, teach one, which was once the norm. Cardiothoracic surgery continues to become more specialized and the patients more complex with greater scrutiny of outcomes. There are many challenges that are faced in contemporary CT training to make intraoperative teaching harder than ever.


Assuntos
Internato e Residência , Cirurgia Torácica/educação , Procedimentos Cirúrgicos Torácicos/educação , Competência Clínica , Medicina Defensiva , Humanos , Internato e Residência/organização & administração , Salas Cirúrgicas , Autonomia Profissional , Fatores de Tempo
20.
Clin Diabetes ; 37(2): 131-141, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31057219

RESUMO

IN BRIEF The number of medications used to treat diabetes has increased dramatically in the past 15 years. With so many options that have shown significant A1C improvement, it is important to consider side effects, precautions, and additional benefits these agents may offer. This article is a review of some of the most compelling literature available on the nonglycemic benefits of sulfonylureas, thiazolidinediones, biguanides, glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase 4 inhibitors, and sodium-glucose cotransporter 2 inhibitors. Other classes of antihyperglycemic agents, such as dopamine agonists, meglitinides, and amylin agonists, are not discussed in this article.

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