The Effects of Combined Movement and Storytelling Intervention on Motor Skills in South Asian and White Children Aged 5–6 Years Living in the United Kingdom

Early motor development has an important role in promoting physical activity (PA) during childhood and across the lifespan. Children from South Asian backgrounds are less active and have poorer motor skills, thus identifying the need for early motor skill instruction. This study examines the effect of a movement and storytelling intervention on South Asian children’s motor skills. Following ethics approval and consent, 39 children (46% South Asian) participated in a 12-week movement and storytelling intervention. Pre and post, seven motor skills (run, jump, throw, catch, stationary dribble, roll, and kick) were assessed using Children’s Activity and Movement in Preschool Study protocol. At baseline, South Asian children had poorer performance of motor skills. Following the intervention, all children improved their motor skills, with a bigger improvement observed for South Asian children. Early intervention provided remedial benefits to delays in motor skills and narrowed the motor skills gap in ethnic groups

Post-prandial hyperlipidaemia results in systemic nitrosative stress and impaired cerebrovascular function in the aged

Post-prandial hyperlipidaemia (PPH) acutely impairs systemic vascular endothelial function, potentially attributable to a free radical-mediated reduction in vascular nitric oxide (NO) bioavailability (oxidative-nitrosative stress). However, it remains to be determined whether this extends to the cerebrovasculature. To examine this, 38 (19 young (≤35 years) and 19 aged (≥60 years)) healthy males were recruited. Cerebrovascular function (middle cerebral artery velocity, MCAv) and cerebrovascular reactivity to hypercapnea (CVRCO2Hyper) and hypocapnea (CVRCO2Hypo) were determined via trans-cranial Doppler ultrasound and capnography. Venous blood samples were obtained for the assessment of triglycerides (photometry), glucose (photometry), insulin (radioimmunoassay), ascorbate free radical (A•-, electron paramagnetic resonance spectroscopy) and nitrite (NO2 -, ozone-based chemiluminescence) in the fasted state prior to and 4 h following consumption of a standardized high-fat meal (1362 kcal; 130 g of fat). Circulating triglycerides, glucose and insulin increased in both groups following the high-fat meal (P < 0.05), with triglycerides increasing by 1.37 ± 1.09 mmol/l in the young and 1.54 ± 1.00 mmol/l in the aged (P < 0.05). This resulted in an increased systemic formation of free radicals in the young (P < 0.05) but not the aged (P > 0.05) and corresponding reduction in NO2 - in both groups (P < 0.05). While the meal had no effect on MCAv in either age group, CVRCO2Hyper was selectively impaired in the aged (P < 0.05). These findings indicate that PPH causes acute cerebrovascular dysfunction in the aged subsequent to systemic nitrosative stress

Existence of long-lasting experience-dependent plasticity in endocrine cell networks

Experience-dependent plasticity of cell and tissue function is critical for survival by allowing organisms to dynamically adjust physiological processes in response to changing or harsh environmental conditions. Despite the conferred evolutionary advantage, it remains unknown whether emergent experience-dependent properties are present in cell populations organized as networks within endocrine tissues involved in regulating body-wide homeostasis. Here we show, using lactation to repeatedly activate a specific endocrine cell network in situ in the mammalian pituitary, that templates of prior demand are permanently stored through stimulus-evoked alterations to the extent and strength of cell–cell connectivity. Strikingly, following repeat stimulation, evolved population behaviour leads to improved tissue output. As such, long-lasting experience-dependent plasticity is an important feature of endocrine cell networks and underlies functional adaptation of hormone release

Targeted mitochondrial therapy using MitoQ shows equivalent renoprotection to angiotensin converting enzyme inhibition but no combined synergy in diabetes.

Mitochondrial dysfunction is a pathological mediator of diabetic kidney disease (DKD). Our objective was to test the mitochondrially targeted agent, MitoQ, alone and in combination with first line therapy for DKD. Intervention therapies (i) vehicle (D); (ii) MitoQ (DMitoQ;0.6 mg/kg/day); (iii) Ramipril (DRam;3 mg/kg/day) or (iv) combination (DCoAd) were administered to male diabetic db/db mice for 12 weeks (n = 11-13/group). Non-diabetic (C) db/m mice were followed concurrently. No therapy altered glycaemic control or body weight. By the study end, both monotherapies improved renal function, decreasing glomerular hyperfiltration and albuminuria. All therapies prevented tubulointerstitial collagen deposition, but glomerular mesangial expansion was unaffected. Renal cortical concentrations of ATP, ADP, AMP, cAMP, creatinine phosphate and ATP:AMP ratio were increased by diabetes and mostly decreased with therapy. A higher creatine phosphate:ATP ratio in diabetic kidney cortices, suggested a decrease in ATP consumption. Diabetes elevated glucose 6-phosphate, fructose 6-phosphate and oxidised (NAD+ and NADP+) and reduced (NADH) nicotinamide dinucleotides, which therapy decreased generally. Diabetes increased mitochondrial oxygen consumption (OCR) at complex II-IV. MitoQ further increased OCR but decreased ATP, suggesting mitochondrial uncoupling as its mechanism of action. MitoQ showed renoprotection equivalent to ramipril but no synergistic benefits of combining these agents were shown

CCL2-driven inflammation increases mammary gland stromal density and cancer susceptibility in a transgenic mouse model.

Abstract Background Macrophages play diverse roles in mammary gland development and breast cancer. CC-chemokine ligand 2 (CCL2) is an inflammatory cytokine that recruits macrophages to sites of injury. Although CCL2 has been detected in human and mouse mammary epithelium, its role in regulating mammary gland development and cancer risk has not been explored. Methods Transgenic mice were generated wherein CCL2 is driven by the mammary epithelial cell-specific mouse mammary tumour virus 206 (MMTV) promoter. Estrous cycles were tracked in adult transgenic and non-transgenic FVB mice, and mammary glands collected at the four different stages of the cycle. Dissected mammary glands were assessed for cyclical morphological changes, proliferation and apoptosis of epithelium, macrophage abundance and collagen deposition, and mRNA encoding matrix remodelling enzymes. Another cohort of control and transgenic mice received carcinogen 7,12-Dimethylbenz(a)anthracene (DMBA) and tumour development was monitored weekly. CCL2 protein was also quantified in paired samples of human breast tissue with high and low mammographic density. Results Overexpression of CCL2 in the mammary epithelium resulted in an increased number of macrophages, increased density of stroma and collagen and elevated mRNA encoding matrix remodelling enzymes lysyl oxidase (LOX) and tissue inhibitor of matrix metalloproteinases (TIMP)3 compared to non-transgenic controls. Transgenic mice also exhibited increased susceptibility to development of DMBA-induced mammary tumours. In a paired sample cohort of human breast tissue, abundance of epithelial-cell-associated CCL2 was higher in breast tissue of high mammographic density compared to tissue of low mammographic density. Conclusions Constitutive expression of CCL2 by the mouse mammary epithelium induces a state of low level chronic inflammation that increases stromal density and elevates cancer risk. We propose that CCL2-driven inflammation contributes to the increased risk of breast cancer observed in women with high mammographic density

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Acute mental stress and its impact on systemic vascular endothelial function in obese adults

Background and aims: Everyday life stressors such as acute mental stress can result in transient impairments in vascular endothelial function (2). Similarly, obesity is known to impair arterial smooth muscle function (1). However, their combined effect remains unknown. To investigate this, we determined to what extent a battery of neuropsychometric tests further compounded vascular endothelial dysfunction in obese adults related to non-obese controls. Methods: Eight obese [26 (mean) ± 8 (SD) years old; BMI = 33 ± 4] and 8 non-obese (21 ± 4 years old; BMI = 25 ± 3) male participants were recruited. Brachial artery flow-mediated dilatation (FMD, Acuson P50, Siemens) was measured 1 hour before and immediately following a standardised battery of neuropsychometric tests. Following a 1-min baseline, the occluding cuff (distal) was inflated (>250mmHg) for 5 min and a subsequently released for 5-min into recovery. Brachial artery diameter and flow were recorded continuously throughout the test. Baseline data correspond to the 1-min average pre cuff inflation and peak diameter was measured as the average of the highest 3 values recorded. Data were analysed using automated edge-detection and wall-tracking software (Brachial Tools, Medical Imaging Application). Following confirmation of distribution normality (Shapiro-Wilk W tests), data were analysed using a 2-way (Time x Group) repeated measures ANOVA. Data are expressed as mean ± SD with significance set at P < 0.05. Results: Psychometric stress was shown to impair FMD (Pre: 5.3 ± 1.4% vs. Post: 4.4 ± 1.4%, P < 0.05). The obese group also displayed a lower FMD than their non-obese peers during both FMD tests (P<0.05). The obese further exhibited a decrease in baseline flow from 0.11 ± 0.02 m/sec before to 0.08 ± 0.02 m/sec after acute mental stress (P<0.05). Conclusion: The present results confirmed that acute mental stress impairs systemic vascular endothelial function. Contrary to our original hypothesis, this impairment was not further compounded by obesity