The non-inferiority of combined breast conservation surgery (BCS) and radiotherapy (breast conservation therapy or BCT) compared to mastectomy in sporadic breast cancer cases is well recognised. ...Uncertainty remains regarding optimal surgical practice in BRCA mutation carriers.
To evaluate the oncological safety of combined BCT versus mastectomy in BRCA mutation carriers following breast cancer diagnosis.
A systematic review was performed as per PRISMA and MOOSE guidelines. Observational studies comparing BCS and mastectomy in BRCA carriers were identified. Dichotomous variables were pooled as odds ratios (OR) using the Mantel–Haenszel method. Log hazard ratios (lnHR) for locoregional recurrence (LRR), contralateral breast cancer, disease-free and overall survival and their standard errors were calculated from Kaplan-Meier or cox-regression analyses and pooled using the inverse variance method.
Twenty three studies of 3807 patients met inclusion criteria; 2200 (57.7%) were BRCA1 and 1212 (31.8%) were BRCA2 carriers. Median age at diagnosis was 41 years with 96 months follow up. BCS was performed on 2157 (56.7%) while 1408 (41.5%) underwent mastectomy. An increased risk of LRR was observed in patients treated with BCS (HR:4.54, 95% Confidence Interval: 2.77–7.42, P < 0.001, heterogeneity (I2) = 0%). However, the risks of contralateral breast cancer (HR:1.51, 95%CI: 0.44–5.11, P = 0.510, I2 = 80%), disease recurrence (HR:1.16, 95%CI: 0.78–1.72, P = 0.470, I2 = 44%), disease-specific recurrence (HR:1.58, 95%CI: 0.79–3.15, P = 0.200, I2 = 38%) and death (HR:1.10, 95%CI: 0.72–1.69, P = 0.660, I2 = 38%) were equivalent for combined BCT and mastectomy.
Survival outcomes following combined BCT is comparable to mastectomy in BRCA carriers. However, the risk of LRR is increased. Patient counselling should be tailored to incorporate these findings.
•BRCA carriers see similar survival after breast conservation therapy and mastectomy.•Locoregional recurrence rates are increased following breast conservation.•Surgical counselling may reflect these findings for BRCA mutation carriers.
Introduction
Studies utilizing beta-hydroxy-beta-methylbutyrate (HMB) supplementation in trained populations are limited. No long-term studies utilizing HMB free acid (HMB-FA) have been conducted. ...Therefore, we investigated the effects of 12 weeks of HMB-FA supplementation on skeletal muscle hypertrophy, body composition, strength, and power in trained individuals. We also determined the effects of HMB-FA on muscle damage and performance during an overreaching cycle.
Methods
A three-phase double-blind, placebo- and diet-controlled randomized intervention study was conducted. Phase 1 was an 8-week-periodized resistance-training program; Phase 2 was a 2-week overreaching cycle; and Phase 3 was a 2-week taper. Muscle mass, strength, and power were examined at weeks 0, 4, 8, and 12 to assess the chronic effects of HMB-FA; and assessment of these, as well as cortisol, testosterone, and creatine kinase (CK) was performed at weeks 9 and 10 of the overreaching cycle.
Results
HMB-FA resulted in increased total strength (bench press, squat, and deadlift combined) over the 12-week training (77.1 ± 18.4 vs. 25.3 ± 22.0 kg,
p
< 0.001); a greater increase in vertical jump power (991 ± 168 vs. 630 ± 167 W,
p
< 0.001); and increased lean body mass gain (7.4 ± 4.2 vs. 2.1 ± 6.1 kg,
p
< 0.001) in HMB-FA- and placebo-supplemented groups, respectively. During the overreaching cycle, HMB-FA attenuated increases in CK (−6 ± 91 vs. 277 ± 229 IU/l,
p
< 0.001) and cortisol (−0.2 ± 2.9 vs. 4.5 ± 1.7 μg/dl,
p
< 0.003) in the HMB-FA- and placebo-supplemented groups, respectively.
Conclusions
These results suggest that HMB-FA enhances hypertrophy, strength, and power following chronic resistance training, and prevents decrements in performance following the overreaching.
ABSTRACTWilson, JM, Duncan, NM, Marin, PJ, Brown, LE, Loenneke, JP, Wilson, SMC, Jo, E, Lowery, RP, and Ugrinowitsch, C. Meta-analysis of postactivation potentiation and powerEffects of conditioning ...activity, volume, gender, rest periods, and training status. J Strength Cond Res 27(3)854–859, 2013—There is no clear agreement regarding the ideal combination of factors needed to optimize postactivation potentiation (PAP) after a conditioning activity. Therefore, a meta-analysis was conducted to evaluate the effects of training status, volume, rest period length, conditioning activity, and gender on power augmentation due to PAP. A total of 141 effect sizes (ESs) for muscular power were obtained from a total of 32 primary studies, which met our criteria of investigating the effects of a heavy preconditioning activity on power in randomized human trials. The mean overall ES for muscle power was 0.38 after a conditioning activity (p < 0.05). Significant differences were found between moderate intensity (60–84%) 1.06 and heavy intensity (>85%) 0.31 (p < 0.05). There were overall significant differences found between single sets 0.24 and multiple sets 0.66 (p < 0.05). Rest periods of 7–10 minutes (0.7) after a conditioning activity resulted in greater ES than 3–7 minutes (0.54), which was greater than rest periods of >10 minutes (0.02) (p < 0.05). Significant differences were found between untrained 0.14 and athletes 0.81 and between trained 0.29 and athletes. The primary findings of this study were that a conditioning activity augmented power output, and these effects increased with training experience, but did not differ significantly between genders. Moreover, potentiation was optimal after multiple (vs. single) sets, performed at moderate intensities, and using moderate rest periods lengths (7–10 minutes).
Opioid use disorder (OUD) is associated with the emergence of persistent negative emotional states during drug abstinence that drive compulsive drug taking and seeking. Functional magnetic resonance ...imaging (fMRI) in rats identified neurocircuits that were activated by stimuli that were previously paired with heroin withdrawal. The activation of amygdala and hypothalamic circuits was related to the degree of heroin dependence, supporting the significance of conditioned negative affect in sustaining compulsive-like heroin seeking and taking and providing neurobiological insights into the drivers of the current opioid crisis.
Summary
Objective
The objective of this study is to summarize evidence for strategies designed to reduce sugar‐sweetened beverage (SSB) consumption among children aged 0 to 5 years.
Data sources
...PubMed, Web of Science, EMBASE, CINAHL, ERIC, Cab s and the Cochrane Central Register of Controlled Trials are the electronic databases searched in this systematic review.
Study selection
Each included study evaluated an intervention to reduce SSB consumption in children aged 0 to 5 years, was conducted in a high‐income country and was published between 1 January 2000 and 15 December 2017.
Data synthesis
Twenty‐seven studies met the inclusion criteria. The primary intervention settings were healthcare (n = 11), preschool/daycare (n = 4), home (n = 3), community venues (n = 3) and other settings (n = 6). Overarching strategies which successfully reduced SSB consumption included (i) in‐person individual education, (ii) in‐person group education, (iii) passive education (e.g. pamphlets), (iv) use of technology, (v) training for childcare/healthcare providers and (vi) changes to the physical access of beverages. Studies were of moderate methodological quality (average score of 20.7/29.0 for randomized studies; 3.1/9.0 for non‐randomized studies).
Conclusions
Evidence suggests that interventions successful at reducing SSB consumption among 0‐year to 5‐year olds often focused on vulnerable populations, were conducted in preschool/daycare settings, specifically targeted only SSBs or only oral hygiene, included multiple intervention strategies and had higher intervention intensity/contact time.
Consumption of moderate amounts of animal-derived protein has been shown to differently influence skeletal muscle hypertrophy during resistance training when compared with nitrogenous and ...isoenergetic amounts of plant-based protein administered in small to moderate doses. Therefore, the purpose of the study was to determine if the post-exercise consumption of rice protein isolate could increase recovery and elicit adequate changes in body composition compared to equally dosed whey protein isolate if given in large, isocaloric doses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The molecular era has identified four breast cancer subtypes. Luminal A breast cancer (LABC) is defined by estrogen-receptor positive (ER+), progesterone-receptor positive (PgR+) and human epidermal ...growth factor receptor-2 negative (HER2-) tumours; these cancers are the most common and carry favourable prognoses.
To describe clinicopathologic features, oncological outcome and relapse patterns in LABC.
Consecutive female patients diagnosed with ER/PgR+/HER2-, lymph node negative (LN-) breast cancer between 2005 and 2015 were included. Clinicopathological and recurrence data was recorded using descriptive statistics. Oncological outcome was determined using Kaplan-Meier and Cox-regression analyses.
Analysis was performed for 849 patients with median follow-up of 102.1 months. Mean disease-free (DFS) and overall survival (OS) were 85.8% and 91.8%. Seventy patients died during this study (8.2%), while 58 patients had recurrence; 7 had local recurrence (0.8%) and 51 had distant recurrence (DDR) (6.0%). Patients developing DDR were likely to be postmenopausal (P = 0.028), present symptomatically (P < 0.001) and have larger tumours (P < 0.001). The mean time to DDR was 65.7 months, with fatal recurrence occurring in 66.6% of patients with DDR (34/51). Systemic chemotherapy prescription did not influence DDR (P = 0.053). Age >65 (hazards ratio (HR):1.66, 95% Confidence Interval (CI):1.07–2.55, P = 0.022), presenting symptomatically (HR:2.28, 95%CI:1.21–4.29, P = 0.011) and tumour size >20 mm (HR:1.81, 95%CI:1.25–2.62, P = 0.002) predicted DFS, while age>65 (HR:2.60, 95%CI:1.49–4.53, P = 0.001) and being postmenopausal at diagnosis (HR:3.13, 95%CI:1.19–8.22, P = 0.020) predicted OS.
Our series demonstrated excellent survival outcomes for patients diagnosed with LN- LABC after almost a decade of follow-up. However, following DDR, fatal progression is often imminent.
•Surgical resection is imperative to achieve locoregional control in breast cancer.•Large index tumour burden increases risk of systemic metastatic dissemination.•50% suffer non-cancer related death; the era of onco-cardiology and oncogeriatrics.
ABSTRACTLowery, RP, Joy, JM, Rathmacher, JA, Baier, SM, Fuller, JC Jr, Shelley, MC II, Jäger, R, Purpura, M, Wilson, SMC, and Wilson, JM. Interaction of beta-hydroxy-beta-methylbutyrate free acid and ...adenosine triphosphate on muscle mass, strength, and power in resistance trained individuals. J Strength Cond Res 30(7)1843–1854, 2016—Adenosine-5′-triphosphate (ATP) supplementation helps maintain performance under high fatiguing contractions and with greater fatigue recovery demands also increase. Current evidence suggests that the free acid form of β-hydroxy-β-methylbutyrate (HMB-FA) acts by speeding regenerative capacity of skeletal muscle after high-intensity or prolonged exercise. Therefore, we investigated the effects of 12 weeks of HMB-FA (3 g) and ATP (400 mg) administration on lean body mass (LBM), strength, and power in trained individuals. A 3-phase double-blind, placebo-, and diet-controlled study was conducted. Phases consisted of an 8-week periodized resistance training program (phase 1), followed by a 2-week overreaching cycle (phase 2), and a 2-week taper (phase 3). Lean body mass was increased by a combination of HMB-FA/ATP by 12.7% (p < 0.001). In a similar fashion, strength gains after training were increased in HMB-FA/ATP-supplemented subjects by 23.5% (p < 0.001). Vertical jump and Wingate power were increased in the HMB-FA/ATP-supplemented group compared with the placebo-supplemented group, and the 12-week increases were 21.5 and 23.7%, respectively. During the overreaching cycle, strength and power declined in the placebo group (4.3–5.7%), whereas supplementation with HMB-FA/ATP resulted in continued strength gains (1.3%). In conclusion, HMB-FA and ATP in combination with resistance exercise training enhanced LBM, power, and strength. In addition, HMB-FA plus ATP blunted the typical response to overreaching, resulting in a further increase in strength during that period. It seems that the combination of HMB-FA/ATP could benefit those who continuously train at high levels such as elite athletes or military personnel.
The purpose of the present study was to determine the effects of short-term supplementation with the free acid form of b-hydroxyb-methylbutyrate (HMB-FA) on indices of muscle damage, protein ...breakdown, recovery and hormone status following a high-volume resistance training session in trained athletes. A total of twenty resistance-trained males were recruited to participate in a high-volume resistance training session centred on full squats, bench presses and dead lifts. Subjects were randomly assigned to receive either 3 g/d of HMB-FA or a placebo. Immediately before the exercise session and 48 h post-exercise, serum creatine kinase (CK), urinary 3-methylhistadine (3-MH), testosterone, cortisol and perceived recovery status (PRS) scale measurements were taken. The results showed that CK increased to a greater extent in the placebo (329%) than in the HMB-FA group (104%) (P¼0·004, d ¼ 1·6). There was also a significant change for PRS, which decreased to a greater extent in the placebo (9·1 (SEM 0·4) to 4·6 (SEM 0·5)) than in the HMB-FA group (9·1 (SEM 0·3) to 6·3 (SEM 0·3)) (P¼0·005, d ¼ 20·48). Muscle protein breakdown, measured by 3-MH analysis, numerically decreased with HMB-FA supplementation and approached significance (P¼0·08, d ¼ 0·12). There were no acute changes in plasma total or free testosterone, cortisol or C-reactive protein. In conclusion, these results suggest that an HMB-FA supplement given to trained athletes before exercise can blunt increases in muscle damage and prevent declines in perceived readiness to train following a high-volume, muscle-damaging resistance-training session.
Opioid misuse is at historically high levels in the United States, with inhalation (ie, smoking and vaping) being one of the most common routes of consumption. We developed and validated a novel ...preclinical model of opioid self-administration by inhalation that does not require surgery and reliably produces somatic and motivational signs of dependence. Rats were trained to perform an operant response (nosepoke) to receive 10 s of vaporized sufentanil, a potent opioid, in 2 h daily sessions. Rats readily and concentration-dependently self-administered vaporized sufentanil. Rats exhibited a significant increase in responding for sufentanil when given the preferential μ-opioid receptor inverse agonist naloxone, suggesting the participation of μ-opioid receptors in the reinforcing properties of sufentanil vapor. Serum sufentanil concentrations significantly correlated with the number of sufentanil vapor deliveries. Rats that were given long access (LgA; 12 h/day) but not short access (ShA; 1 h/day) to vaporized sufentanil escalated their drug intake over time and exhibited both naloxone-precipitated somatic signs of opioid withdrawal and spontaneous withdrawal-induced mechanical hypersensitivity. After 6 months of forced drug abstinence, LgA rats returned to pre-escalation baseline levels of responding for sufentanil and mechanical sensitivity. Upon subsequent re-escalation (ie, after the return to extended access to sufentanil vapor), LgA rats again developed naloxone-precipitated somatic signs of withdrawal and spontaneous withdrawal-induced mechanical hypersensitivity. These findings demonstrate that the operant sufentanil vapor self-administration model has both face and construct validity and therefore will be useful for investigating the neurobiological basis of opioid addiction.