Patients requiring surgery for locally advanced rectal cancer often additionally undergo neoadjuvant chemoradiotherapy (NACRT), of which the effects on physical fitness are unknown. The aim of this ...feasibility and pilot study was to investigate the effects of NACRT and a 6 week structured responsive exercise training programme (SRETP) on oxygen uptake (V˙O2) at lactate threshold ( θˆL) in such patients.
We prospectively studied 39 consecutive subjects (27 males) with T3–4/N+ resection margin threatened rectal cancer who completed standardized NACRT. Subjects underwent cardiopulmonary exercise testing at baseline (pre-NACRT), at week 0 (post-NACRT), and week 6 (post-SRETP). Twenty-two subjects undertook a 6 week SRETP on a training bike (three sessions per week) between week 0 and week 6 (exercise group). These were compared with 17 contemporaneous non-randomized subjects (control group). Changes in V˙O2 at θˆL over time and between the groups were compared using a compound symmetry covariance linear mixed model.
Of 39 recruited subjects, 22 out of 22 (exercise) and 13 out of 17 (control) completed the study. There were differences between the exercise and control groups at baseline age, ASA score physical status, World Health Organisation performance status, and Colorectal Physiologic and Operative Severity Score for the Enumeration of Mortality and Morbidity (CR-POSSUM) predicted mortality. In all subjects, V˙O2 at θˆL significantly reduced between baseline and week 0 −1.9 ml kg−1 min−1; 95% confidence interval (CI) −1.3, −2.6; P<0.0001. In the exercise group, V˙O2 at θˆL significantly improved between week 0 and week 6 (+2.1 ml kg−1 min−1; 95% CI +1.3, +2.9; P<0.0001), whereas the control group values were unchanged (−0.7 ml kg−1 min−1; 95% CI −1.66, +0.37; P=0.204).
NACRT before rectal cancer surgery reduces physical fitness. A structured exercise intervention is feasible post-NACRT and returns fitness to baseline levels within 6 weeks.
NCT: 01325909.
Most studies of logistics outsourcing have focused on cost reduction, while few studies have reported on service benefits. This study empirically examines if outsourcing different logistics ...activities results in differences in logistics service performance. We identify and analyze the outsourcing of four levels of logistics activities: transportation (level 1), packaging (level 2), transportation management (level 3), and distribution network management (level 4). A research framework was formulated to discuss the effect of the outsourcing decision of different levels on perceived logistics service performance and includes the moderating role that supply chain complexity may play in the proposed relationships. Our findings show that outsourcing has no direct impact on service performance (delivery reliability, flexibility and lead-time) in any of the four levels. However, the performance when outsourcing level 4 activities increases with an increasing degree of demand complexity. Furthermore, chilled foods have higher service performance than non-chilled foods. These findings show the complex relationships between levels of outsourcing, performance and supply chain characteristics.
Blood calcium concentration is maintained within a narrow range despite large variations in dietary input and body demand. The Transient Receptor Potential ion channel TRPV5 has been implicated in ...this process. We report here that TRPV5 is stimulated by the mammalian hormone klotho. Klotho, a β-glucuronidase, hydrolyzes extracellular sugar residues on TRPV5, entrapping the channel in the plasma membrane. This maintains durable calcium channel activity and membrane calcium permeability in kidney. Thus, klotho activates a cell surface channel by hydrolysis of its extracellular N-linked oligosaccharides.
The use of antenatal steroid therapy is common in pregnancy. In early pregnancy, steroids may be used in women for the treatment of recurrent miscarriage or fetal abnormalities such as congenital ...adrenal hyperplasia. In mid-late pregnancy, the antenatal administration of corticosteroids to expectant mothers in anticipation of preterm birth is one of the most important advances in perinatal medicine; antenatal corticosteroids are now standard care for pregnancies at risk of premature delivery in high- and middle-income countries. The widespread uptake of this therapy is due to a compelling body of evidence demonstrating improved neonatal outcomes following antenatal corticosteroid exposure, stemming most notably from corticosteroid-driven maturation of fetal pulmonary function. As we approach the 50th anniversary of landmark work in this area by Liggins and Howie, it is apparent that much remains to be understood with regards to how we might best apply antenatal corticosteroid therapy to improve pregnancy outcomes at both early and mid to late gestation.
Drawing on advances in laboratory science, pre-clinical and clinical studies, we performed a narrative review of the scientific literature to provide a timely update on the benefits, risks and uncertainties regarding antenatal corticosteroid use in pregnancy. Three, well-established therapeutic uses of antenatal steroids, namely recurrent miscarriage, congenital adrenal hyperplasia and preterm birth, were selected to frame the review.
Even the most well-established antenatal steroid therapies lack the comprehensive pharmacokinetic and dose-response data necessary to optimize dosing regimens. New insights into complex, tissue-specific corticosteroid signalling by genomic-dependent and independent mechanisms have not been used to inform corticosteroid treatment strategies. There is growing evidence that some fetal corticosteroid treatments are either ineffective, or may result in adverse outcomes, in addition to lasting epigenetic changes in a variety of homeostatic mechanisms. Nowhere is the need to better understand the intricacies of corticosteroid therapy better conveyed than in the findings of Althabe and colleagues who recently reported an increase in overall neonatal mortality and maternal morbidity in association with antenatal corticosteroid administration in low-resource settings.
New research to clarify the benefits and potential risks of antenatal corticosteroid therapy is urgently needed, especially with regard to corticosteroid use in low-resource environments. We conclude that there is both significant scope and an urgent need for further research-informed refinement to the use of antenatal corticosteroids in pregnancy.
Context:
Randomized controlled trials in nonalcoholic fatty liver disease (NAFLD) have shown that regular exercise, even without calorie restriction, reduces liver steatosis. A previous study has ...shown that 16 weeks of supervised exercise training in NAFLD did not affect total very low-density lipoprotein (VLDL) kinetics.
Objective:
The objective of the study was to determine the effect of exercise training on intrahepatocellular fat (IHCL) and the kinetics of large triglyceride (TG)-rich VLDL1 and smaller denser VLDL2, which has a lower TG content.
Design:
This was a 16-week randomized controlled trial.
Patients:
A total of 27 sedentary patients with NAFLD participated in the trial.
Intervention:
The intervention was composed of supervised exercise with moderate-intensity aerobic exercise or conventional lifestyle advice (control).
Main Outcome:
VLDL1 and VLDL2-TG and apolipoprotein B (apoB) kinetics were investigated using stable isotopes before and after the intervention.
Results:
In the exercise group, maximal oxygen uptake increased by 31% ± 6% (mean ± SEM) and IHCL decreased from 19.6% (14.8%, 30.0%) to 8.9% (5.4%, 17.3%) (median interquartile range) with no significant change in maximal oxygen uptake or IHCL in the control group (change between groups, P < .001 and P = .02, respectively). Exercise training increased VLDL1-TG and apoB fractional catabolic rates, a measure of clearance, (change between groups, P = .02 and P = .01, respectively), and VLDL1-apoB production rate (change between groups, P = .006), with no change in VLDL1-TG production rate. Plasma TG did not change in either group.
Conclusion:
An increased clearance of VLDL1 may contribute to the significant decrease in liver fat after 16 weeks of exercise in NAFLD. A longer duration or higher-intensity exercise interventions may be needed to lower the plasma TG and VLDL production rate.
A 16-week exercise improved fitness and reduced liver fat by 50% in men with NAFLD and increased clearance of both VLDL1 TG and apoB. However the liver continued to export large amounts of VLDL-TG.
Early-life gut microbial colonisation is known to influence host physiology and development, shaping its phenotype. The developing gastro-intestinal tract of neonatal piglets provides a "window of ...opportunity" for programming their intestinal microbiota composition and corresponding intestinal development. Here, we investigated the impact of early feeding on jejunum and colon microbiota composition, and intestinal maturation in suckling piglets. From two days of age, early-fed (EF; n = 6 litters) piglets had access to solid feed containing a mixture of fibres till weaning (day29) in addition to sow's milk, whereas the control (CON; n = 6 litters) piglets exclusively fed on sow's milk. Early feeding elicited a significant impact on the colon microbiota, whereas no such effect was seen in the jejunal and ileal microbiota. Quantified eating behavioural scores could significantly explain the variation in microbiota composition of EF piglets and support their classification into good, moderate, and bad eaters. Members of the Lachnospiraceae family, and the genera Eubacterium, Prevotella, and Ruminococcus were quantitatively associated with eating scores. EF piglets were found to have a decreased pH in caecum and colon, which coincided with increased short-chain fatty acid (SCFA) concentrations. Moreover, they also had increased weights and lengths of several intestinal tract segments, as well as a decreased villus-crypt ratio in jejunal mucosa and an increased abundance of proliferative cells in colon mucosa. The approaches in this study indicate that early feeding of a mixed-fibre (pre-weaning) diet changes the microbiota composition, pH, and fermentation products in the distal gut of piglets, while it also alters both macroscopic and microscopic intestinal measurements. These results exemplify the potential of early feeding to modulate intestinal development in young piglets.
Because cerebral morphological abnormalities in major depressive disorder (MDD) may be modulated by antidepressant treatment, inclusion of medicated patients may have biased previous meta-analyses of ...voxel-based morphometry (VBM) studies. A meta-analysis of VBM studies on medication-free MDD patients should be able to distinguish the morphological features of the disease itself from those of treatment.
A systematic search was conducted for the relevant studies. Effect-size signed differential mapping was applied to analyse the grey matter differences between all medication-free MDD patients and healthy controls. Meta-regression was used to explore the effects of demographics and clinical characteristics.
A total of 14 datasets comprising 400 medication-free MDD patients and 424 healthy controls met the inclusion criteria. The pooled meta-analysis and subgroup meta-analyses showed robustly reduced grey matter in prefrontal and limbic regions in MDD. Increased right thalamus volume was only seen in first-episode medication-naive patients, and increased grey matter in the bilateral anterior cingulate cortex only in medication wash-out patients. In meta-regression analyses the percentage of female patients in each study was negatively correlated with reduced grey matter in the right hippocampus.
By excluding interference from medication effects, the present study identified grey matter reduction in the prefrontal-limbic network in MDD. The subgroup meta-analysis results suggest that an increased right thalamus volume might be a trait directly related to MDD, while an increased anterior cingulate cortex volume might be an effect of medication. The meta-regression results perhaps reveal the structural underpinning of the sex differences in epidemiological and clinical aspects of MDD.
Resistant starch (RS) is highly fermentable by microbiota in the colon, resulting in the production of SCFAs. RS is thought to mediate a large proportion of its health benefits, including increased ...satiety, through the actions of SCFAs. The aim of this study was to investigate the effects of a diet high in RS on luminal microbiota composition, luminal SCFA concentrations, and the expression of host genes involved in SCFA uptake, SCFA signaling, and satiety regulation in mucosal tissue obtained from small intestine, cecum, and colon. Twenty adult female pigs were either assigned to a digestible starch (DS) diet or a diet high in RS (34%) for a period of 2 wk. After the intervention, luminal content and mucosal scrapings were obtained for detailed molecular analysis. RS was completely degraded in the cecum. In both the cecum and colon, differences in microbiota composition were observed between DS- and RS-fed pigs. In the colon these included the stimulation of the healthy gut-associated butyrate-producing Faecalibacterium prausnitzii, whereas potentially pathogenic members of the Gammaproteobacteria, including Escherichia coli and Pseudomonas spp., were reduced in relative abundance. Cecal and colonic SCFA concentrations were significantly greater in RS-fed pigs, and cecal gene expression of monocarboxylate transporter 1 (SLC16A1) and glucagon (GCG) was induced by RS. In conclusion, our data show that RS modulates microbiota composition, SCFA concentrations, and host gene expression in pig intestine. Combined, our data provide an enhanced understanding of the interaction between diet, microbiota, and host.
Identification of reliable characteristics of follicle quality and developmental competence has been pursued in numerous studies, but with inconsistent outcomes. Here, we aimed to identify these ...characteristics by analysis of the follicular fluid (FF) steroid profile in relation to cumulus-oocyte complex (COC) morphology and follicle size, followed by molecular substantiation. Multiparous sows at weaning were used to facilitate analysis at the start of the follicular phase of the oestrus cycle. Sows with a higher average follicle size (≥5 mm vs. < 5 mm) had a higher follicular fluid β-estradiol concentration, but did not differ in other measured steroids. Sows with high compared to low percentage high-quality COCs (<70% vs. ≥70% high-quality) had follicular fluid with a higher concentration of β-estradiol, 19-norandrostenedione, progesterone, and α-testosterone, while the concentration of cortisol was lower. Transcriptome analysis of granulosa cells of healthy follicles of sows with a high percentage high-quality COCs showed higher abundance of transcripts involved in ovarian steroidogenesis (e.g., CYP19A2 and 3, POR, VEGFA) and growth (IGF1) and differential abundance of transcripts involved in granulosa cell apoptosis (e.g., GADD45A, INHBB). Differences in aromatase transcript abundance (CYP19A1, 2 and 3) were confirmed at the protein level. In addition, sows with a high percentage high-quality COCs lost less weight during lactation and had higher plasma IGF1 concentration at weaning, which may have affected COC quality. To the best of our knowledge, this study is also the first to report the relation between FF steroid profile and COC quality. Summary sentence Sows with a higher percentage high-quality COCs have a distinct follicular fluid steroid profile and concomitant granulosa cell transcriptome.
The term 'metabolically healthy obese (MHO)' is distinguished using body mass index (BMI), yet BMI is a poor index of adiposity. Some epidemiological data suggest that MHO carries a lower risk of ...cardiovascular disease (CVD) or mortality than being normal weight yet metabolically unhealthy.
We aimed to undertake a detailed phenotyping of individuals with MHO by using imaging techniques to examine ectopic fat (visceral and liver fat deposition) and myocardial function. We hypothesised that metabolically unhealthy individuals (irrespective of BMI) would have adverse levels of ectopic fat and myocardial dysfunction compared with MHO individuals.
Individuals were categorised as non-obese or obese (BMI ⩾30 kg m(-2)) and as metabolically healthy or unhealthy according to the presence or absence of metabolic syndrome.
Sixty-seven individuals (mean±s.d.: age 49±11 years) underwent measurement of (i) visceral, subcutaneous and liver fat using magnetic resonance imaging and proton magnetic resonance spectroscopy, (ii) components of metabolic syndrome, (iii) cardiorespiratory fitness and (iv) indices of systolic and diastolic function using tissue Doppler echocardiography.
Cardiorespiratory fitness was similar between all groups; abdominal and visceral fat was highest in the obese groups. Compared with age- and BMI-matched metabolically healthy counterparts, the unhealthy (lean or obese) individuals had higher liver fat and decreased early diastolic strain rate, early diastolic tissue velocity and systolic strain indicative of subclinical systolic and diastolic dysfunction. The magnitude of dysfunction correlated with the number of components of metabolic syndrome but not with BMI or with the degree of ectopic (visceral or liver) fat deposition.
Myocardial dysfunction appears to be related to poor metabolic health rather than simply BMI or fat mass. These data may partly explain the epidemiological evidence on CVD risk relating to the different obesity phenotypes.
PDF
