Abstract2 ) and comparative normal-weight (BMI, 21.9 Ϯ 0.5 kg/m 2 ) adults 18 to 30 years old (total N ϭ 48) were enrolled. Participants received either daily antioxidant (AOX) treatment (800 IU of vitamin E, 500 mg of vitamin C, 10 mg of -carotene) or placebo (PL) for 8 weeks for a total of four groups. All participants completed a standardized 30-minute cycle exercise bout at baseline and 8 weeks. Exercise-induced changes in lipid hydroperoxide (⌬PEROX), C-reactive protein (⌬CRP), interleukin-6 (⌬IL-6), cholesterol subfractions, triglycerides, total AOX status (⌬TAS), and adiponectin were assessed. Results: Exercise-induced ⌬PEROX was lower in the overweight-AOX group (0.09 nM/kg per min) compared with PL-treated overweight and normal-weight groups (0.98, 0.53 nM/kg per min) by 8 weeks (p Ͻ 0.05). Adiponectin was increased in both overweight and normal-weight AOX groups (22.1% vs. 3.1%; p Ͻ 0.05) but reduced in PL groups. ⌬IL-6, ⌬total cholesterol, and ⌬low-density lipoprotein-cholesterol concentrations during exercise were lower in the AOX-treated groups compared with PL groups (all p Ͻ 0.05). After controlling for BMI, the ⌬total cholesterol, ⌬low-density lipoprotein-cholesterol, ⌬adiponec-tin, and ⌬TAS explained 59.1% of the variance of the regression model of the ⌬PEROX by 8 weeks (total model R 2 ϭ 0.600; p ϭ 0.015). Discussion: AOX lowers exercise-induced oxidative stress in overweight adults. Inflammatory and lipid markers may also be attenuated with AOX. Further studies are needed to determine whether AOX may be used in cardiovascular disease prevention in the overweight population.
Mutant yeast actins were used to determine the role of actin's N-terminal negative charges in force generation. The thin filament was selectively removed from bovine cardiac skinned muscle fibres by gelsolin, and the actin filament was reconstituted from purified G-actin. In this reconstitution, yeast wild-type actin (2Ac: two N-terminal negative charges), yeast mutant actins (3Ac and 4Ac), and rabbit skeletal muscle actin (MAc) were used. The effects of phosphate, ATP and ADP on force development were studied at 25 degrees C. With MAc, isometric tension was 77% of the initial tension owing to the lack of a regulatory system. With 2Ac, isometric tension was 10% of the initial tension; with 3Ac, isometric tension was 23%; and with 4Ac, isometric tension was 44%. Stiffness followed a similar pattern (2Ac < 3Ac < 4Ac < MAc). A similar trend was observed during rigor induction and relaxation. Sinusoidal analysis was performed to obtain the kinetic constants of the cross-bridge cycle. The results showed that the variability of the kinetic constants was < or = 2.5-fold among the 2Ac, 4Ac and MAc muscle models. When the cross-bridge distribution was examined, there was no significant reapportionment among these three models examined. These results indicate that force supported by each cross-bridge is modified by the N-terminal negative charges of actin, presumably via the actomyosin interface. We conclude that two N-terminal negative charges are not adequate, three negative charges are intermediate, and four negative charges are necessary to generate force.
Peripherally located smaller HCC tumours are most likely to experience a > 90% or complete tumour necrosis after TACE. Surprisingly, arterial-phase enhancement and portal venous-phase washout were not significantly predictive of TACE-induced tumour necrosis. The TACE response was not statistically associated with improved survival.
The requirement for repeat TACE is associated with older age, increased HCC tumour burden and subtotal TACE-induced HCC necrosis. Importantly, repeat TACE was not associated with reduced survival.
BackgroundMerkel cell carcinoma (MCC) is a rare and aggressive form of skin cancer. It is an immunogenic tumor as evident by its association with Polyomavirus, immunotherapy response, and increased prevalence in the immunosuppressed population.ObjectiveWe sought to evaluate the impact of known clinicopathological determinants and immunosuppression on the risk of recurrence and mortality of MCC patients.MethodsA retrospective, observational cohort study of patients diagnosed and/or treated with MCC at two tertiary academic institutions. We compared clinicopathological determinants, treatment modalities, and immunosuppression status on clinical outcomes of recurrence, disease‐specific survival, and overall survival.ResultsWe evaluated 90 patients within our study and 34% had a cancer recurrence during follow‐up. Patients with recurrence were significantly more likely to be immunosuppressed (32% vs 5%; P = .001). Estimated 5‐year recurrence was 43%, and immunosuppressed patients were significantly more likely to recur (Hazard ratio [HR] 3.67 [1.80‐7.51]; P < .0001). Immunosuppressed patients had significantly elevated cancer‐specific mortality (HR 6.11[1.61‐23.26]; P = .008).LimitationsRetrospective review with a prolonged observation period and changing treatment modalities.ConclusionImmunocompromised patients had a threefold increased incidence of 5‐year mortality and over twofold increased incidence of any recurrence as non–immunocompromised patients. Patients’ immunosuppressive status should be considered when making decisions regarding treatment, surveillance, and prognostication.
TACE appears to be equally efficacious in cirrhotic patients regardless of their Child's classification based upon equivalent mRECIST measures of tumour necrosis. However, inferior survival after TACE was observed in the Child's B/C group.
Maine et al describe the first national look at surgical outcomes in incarcerated patients in this EAST Multi-center Study. How can we improve trauma and surgical care for this population? #EASTMulticenterStudy #Healthdisparities
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