Safety and efficacy of weight training in recent breast cancer survivors to alter body composition, insulin, and insulin-like growth factor axis proteins.

BACKGROUND: This randomized controlled trial assessed the safety and effects of twice-weekly weight training among recent breast cancer survivors. Outcomes included body size and biomarkers hypothesized to link exercise and breast cancer risk. METHODS: A convenience sample of 85 recent survivors was randomized into immediate and delayed treatment groups. The immediate group trained from months 0 to 12; the delayed treatment group served as a no exercise parallel comparison group from months 0 to 6 and trained from months 7 to 12. Measures at baseline, 6 and 12 months included body weight, height, body fat, lean mass, body fat %, and waist circumference, as well as fasting glucose, insulin, insulin resistance, insulin-like growth factor-I (IGF-I), IGF-II, and IGF-binding protein-1, IGFBP-2, and IGFBP-3. Injury reporting was standardized. RESULTS: The intervention resulted in significant increases in lean mass (0.88 versus 0.02 kg, P < 0.01), as well as significant decreases in body fat % (-1.15% versus 0.23%, P = 0.03) and IGF-II (-6.23 versus 28.28 ng/mL, P = 0.02) comparing immediate with delayed treatment from baseline to 6 months. Within-person changes experienced by delayed treatment group participants during training versus no training were similar. Only one participant experienced a study related injury that prevented continued participation. CONCLUSION: Twice-weekly weight training is a safe exercise program for recent breast cancer survivors that may result in increased muscle mass, as well as decreased body fat % and IGF-II. The implications of these results on cancer recurrence or survival may become more evident with longer exercise intervention trials among breast cancer survivors.     

Proteasome inhibition with bortezomib (PS-341): a phase I study with pharmacodynamic end points using a day 1 and day 4 schedule in a 14-day cycle.

PURPOSE: We performed a phase I study of a day (D) 1 and D4 bortezomib administration once every 2 weeks to determine the recommended phase II dose and toxicity profile, and the extent of 20S proteasome inhibition obtained. PATIENTS AND METHODS: Patients with solid tumors or lymphomas were treated with bortezomib at 0.25 to 1.9 mg/m2 on D1 and D4, every 2 weeks. 20S proteasome levels in blood were assayed at baseline and at 1, 4, and 24 hours postdose in cycle 1. RESULTS: On this D1 and D4 every 2 weeks' schedule, dose-limiting toxicity (DLT) was evident at the 1.75 and 1.9 mg/m2 dose levels, most commonly in patients receiving individual total doses > or = 3.0 mg. The main DLT was peripheral neuropathy evident at the higher doses and in patients previously exposed to neurotoxic agents. Other DLTs included diarrhea and fatigue; grade 3 thrombocytopenia was also noted. Reversible inhibition of 20S proteasome activity was dose dependent and best fit a total dose (mg) per fraction rather than mg/m2; 70% of baseline activity was inhibited by a dose of 3.0 to 3.5 mg given on D1 and on D4 every other week. Antitumor effects short of confirmed partial responses were observed in patients with melanoma, non-small-cell lung cancer, and renal cell carcinoma. CONCLUSION: Bortezomib (PS-341) is a novel antineoplastic agent that is well tolerated at doses not exceeding 3.0 mg (equivalent to 1.75 mg/m2), repeated on D1 and D4 every other week. This dose correlates with 70% inhibition of 20S proteasome activity. DLTs include neuropathy, fatigue, and diarrhea.     

Understanding and clinical application of acute dilation of the left ventricle on ventricular arrhythmias

In this issue of the Journal of Geriatric Cardiology,Yin et al discussed the effects of calcium preconditioning (CPC) and streptomycin (S) on acute dilation of the left ventricle.……     

Evaluation of the sub-acute toxicity of the sclerotium of Lignosus rhinocerus (Cooke), the Tiger Milk mushroom

Ethnopharmacological relevance

Lignosus rhinocerus (known locally as ‘Tiger Milk mushroom’) is the most important medicinal mushroom used by the indigenous communities of Malaysia to treat fever, cough, asthma, cancer, food poisoning and as a general tonic. The sclerotium of the mushroom is the part with medicinal value. Lignosus rhinocerus was hitherto unexploited commercially because of limited supply. Recently, the mushroom was successfully cultivated.

Materials and methods

Sprague Dawley rats (5 rats/group/sex) were fed orally with 250, 500 and 1000 mg/kg TM02, 1000 mg/kg TM03 as well as 1000 mg/kg wild type Lignosus rhinocerus sclerotial powder. Sclerotial powder was orally administered once daily and consecutively for 28 days. Body weight of each animal was measured and any gross behavioral change was observed daily. Hematological and clinical biochemical parameters as well as histopathological analysis were carried out on 29th day.

Results

The results showed that oral administration of the sclerotial powder at daily dose of up to 1000 mg/kg had no adverse effect on the growth rate, hematological and clinical biochemical parameters (including renal and liver function parameters). Histological studies showed that the treatments did not induce any pathological changes in the liver, kidney, heart, spleen and lung of the animals.

Conclusion

In conclusion, our results show that there was no treatment-related sub-acute toxicity in rats following 28-days oral administration of 250, 500 and 1000 mg/kg TM02, 1000 mg/kg TM03 as well as 1000 mg/kg wild type Lignosus rhinocerus sclerotial powder. As the highest tested dose of 1000 mg/kg was not associated with any toxicity concern, the NOAEL dose is higher than 1000 mg/kg.     

“It Got Likes,But I Don’t Think People Understood”: A Qualitative Study of Adolescent Experiences Discussing Type 1 Diabetes on Social Media

Background:The majority of adolescents with type 1 diabetes (T1D) integrate social media engagement into their daily lives. The aim of this study was to explore adolescents’ experiences and perspectives discussing their T1D on social media.Methods:Semi-structured interviews with adolescents with T1D were conducted in person and via telephone. Questions focused on the participant’s experiences utilizing social media to discuss T1D and factors that informed the nature of T1D-related social media engagement. Open coding and thematic content analysis were used to identify emergent themes that aligned with accepted domains of social media affordances.Results:Participants included 35 adolescents with T1D. Adolescents’ experiences related to discussing T1D on social media aligned with four affordances of social media: identity, cognitive, emotional, and social. The identity affordances of social media platforms allowed adolescents to curate online personas that selectively included their diagnosis of T1D, while managing the potential negative emotional and social implications linked to the stigma of T1D. Adolescents who decided to discuss T1D on social media leveraged cognitive affordances by providing and receiving diabetes management advice, emotional affordances by obtaining affirmation from peers, and social affordances by extending their network to include other individuals with T1D.Conclusions:Adolescents with T1D flexibly leverage the affordances offered by social media to access emotional support, information, and identity affirmation resources while navigating stigma-based social consequences. Our findings highlight the value of developing tools to support adolescents with T1D in comfortably discussing and receiving appropriate support about T1D on social media.     

Association of social determinants of health with late diagnosis and survival of patients with pancreatic cancer

BackgroundPancreatic cancer disparities have been described. However, it is unknown if they contribute to a late diagnosis and survival of patients with metastatic disease. Identifying their role is important as it will open the door for interventions. We hypothesize that social determinants of health (SDH) such as income, education, race, and insurance status impact (I) stage of diagnosis of PC (Stage IV vs. other stages), and (II) overall survival (OS) in Stage IV patients.MethodsUsing the National Cancer Database, we evaluated a primary outcome of diagnosis of Stage IV PC and a secondary outcome of OS. Primary predictors included race, income, education, and insurance. Covariates included age, sex and Charlson-Deyo comorbidity score. Univariate, multivariable logistic regression models evaluated risk of a late diagnosis. Univariate, multivariable Cox proportional hazards model examined OS. 95% confidence intervals were used.Results230,877 patients were included, median age of 68 years (SD 12.1). In univariate analysis, a better education, higher income, and insurance decreased the odds of Stage IV PC, while Black race increased it. In multivariable analysis, education [>93% high-school completion (HSC) vs. <82.4%, OR 0.96 (0.93–0.99)] and insurance [private vs. no, OR 0.72 (0.67–0.74)] significantly decreased the risk of a late diagnosis, whereas Black race increased the odds [vs. White, OR 1.09 (1.07–1.12)]. In univariate Cox analysis, having a higher income, insurance and better education improved OS, while Black race worsened it. In multivariable Cox, higher income [>$63,333 (vs. <$40,277), HR 0.87 (0.85–0.89)] and insurance [private vs. no, HR 0.77 (0.74–0.79)] improved OS.ConclusionsSDH impacted the continuum of care for patients with advanced pancreatic cancer, including stage at diagnosis and overall survival.