Regulation of Peripheral Molecular Clocks in Mammalian Tissues and In Vitro Skeletal Muscle Activation of AMP-Activated Protein Kinase via AICAR

Most organisms possess a common molecular machinery that governs cellular and tissue circadian rhythmicity through a roughly 24-hour transcription-translation feedback loop. It is estimated that up to 15 percent of human genes are influenced by the core clock machinery. It is likely, however, that the metabolic networks affected by the molecular clock differ according to body tissue. Recent evidence suggests that peripheral molecular clocks are governed to a greater extent by energy availability than by light and dark cycles. AMP-activated protein kinase (AMPK) acts as a cellular fuel gauge within the cell and is activated in response to exercise and fasting. AMPK can also be pharmacologically activated by 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR). AMPK likely serves as an intermediary between metabolism and the molecular clock due to its activation of the rate-limiting enzyme in Nicotinamide adenine dinucleotide (NAD) biosynthesis, Nicotinamide phosphoribosyltransferase (NAMPT), and its role in PER and CRY degradation. The NAD-dependent histone deacetylase SIRT 1 inhibits the BMAL1-CLOCK complex in a NAMPT-dependent manner.The complex interplay between metabolism and peripheral clocks mediated by AMPK is beginning to be unraveled. AMPK’s tissue-specific influence on the molecular clock in skeletal muscles and other mammalian tissues requires further elucidation as it may provide insight into the etiology and treatment of metabolic disease. [excerpt

Effect of the Shoe Sole on the Vibration Transmitted from the Supporting Surface to the Feet

Vibration transmitted through the foot can lead to vibration white feet, resulting in blanching of the toes and the disruption of blood circulation. Controlled studies identifying industrial boot characteristics effective at attenuating vibration exposure are lacking. This work focused on the evaluation of vibration transmissibility of boot midsole materials and insoles across the range 10-200 Hz at different foot locations. Questionnaires were used to evaluate the comfort of each material. The materials were less effective at attenuating vibration transmitted to the toe region of the foot than the heel. Between 10 and 20 Hz, all midsole materials reduced the average vibration transmitted to the foot. The average transmissibility at the toes above 100 Hz was larger than 1, evidencing that none of the tested material protects the worker from vibration-related risks. There was a poor correlation between the vibration transmissibility and the subjective evaluation of comfort. Future research is needed to identify materials effective for protecting both the toe and the heel regions of the foot. Specific standards for shoe testing are required as well

Pravastatin for early-onset pre-eclampsia:a randomised, blinded, placebo-controlled trial

Objective: Women with pre-eclampsia have elevated circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1). Statins can reduce sFlt-1 from cultured cells and improve pregnancy outcome in animals with a pre-eclampsia-like syndrome. We investigated the effect of pravastatin on plasma sFlt-1 levels during pre-eclampsia. Design: Blinded (clinician and participant), proof of principle, placebo-controlled trial. Setting: Fifteen UK maternity units. Population: We used a minimisation algorithm to assign 62 women with early-onset pre-eclampsia (24 +0–31 +6 weeks of gestation) to receive pravastatin 40 mg daily (n = 30) or matched placebo (n = 32), from randomisation to childbirth. Primary outcome: Difference in mean plasma sFlt-1 levels over the first 3 days following randomisation. Results: The difference in the mean maternal plasma sFlt-1 levels over the first 3 days after randomisation between the pravastatin (n = 27) and placebo (n = 29) groups was 292 pg/ml (95% CI −1175 to 592; P = 0.5), and over days 1–14 was 48 pg/ml (95% CI −1009 to 913; P = 0.9). Women who received pravastatin had a similar length of pregnancy following randomisation compared with those who received placebo (hazard ratio 0.84; 95% CI 0.50–1.40; P = 0.6). The median time from randomisation to childbirth was 9 days [interquartile range (IQR) 5–14 days] for the pravastatin group and 7 days (IQR 4–11 days) for the placebo group. There were three perinatal deaths in the placebo-treated group and no deaths or serious adverse events attributable to pravastatin. Conclusions: We found no evidence that pravastatin lowered maternal plasma sFlt-1 levels once early-onset pre-eclampsia had developed. Pravastatin appears to have no adverse perinatal effects. Tweetable abstract: Pravastatin does not improve maternal plasma sFlt-1 or placental growth factor levels following a diagnosis of early preterm pre-eclampsia #clinicaltrial finds

Validation of smart insoles for the measurement of vibration exposure of workers and athletes

Wearable sensors are becoming increasingly common in daily life for medical care, athletic training, or even daily activity monitoring [1]-[3]. As these systems advance, so do their potential application, but their use for monitoring vibration exposure is limited or absent, despite the adverse effects of vibration on health being well known among the scientific community. To address this deficit, we propose a system of sensorized smart insoles capable of measuring triaxial vibration exposure according to ISO 2631-1. Each insole allows measurement of the vibration exposure and contact pressure at the forefoot and rearfoot, as well as the temperature inside the shoe. We used the insoles to measure the vibration exposure of five male subjects in three different testing conditions: 1) indoor condition (Politecnico di Milano laboratory, atop a triaxial shaker; 2) outdoor condition riding a mountain bike; and 3) skiing. The vibration exposure along the three mutually perpendicular axes was compared with that measured using instrumentation compliant with the current standards (ISO 8041). Results show that the proposed system allows direct monitoring of vibration exposure at the feet, also accounting for the vibration reduction provided by the shoe sole

Spatiotemporal gait parameter changes due to exposure to vertical whole-body vibration

Background: Vertical whole-body vibration (vWBV) during work, recreation, and transportation can have detrimental effects on physical and mental health. Studies have shown that lateral vibration at low frequencies ( 3 Hz). This study seeks to assess the effect of vWBV on spatiotemporal gait parameters at a greater range of frequencies (≤ 30 Hz). Methods: Stride Frequency (SF), Stride Length (SL), and Center of Pressure velocity (CoPv) was measured in seven male subjects (23 ± 4 years, 1.79 ± 0.05 m, 73.9 ± 9.7 kg) during In-Place Walking and nine male subjects (29 ± 7 years, 1.78 ± 0.07 m, 77.8 ± 9.9 kg; mean ± SD) during Treadmill Walking while exposed to vWBV. Load cells measured ground reaction forces during In-Place Walking and sensorized insoles acquired under-foot pressure during Treadmill Walking. Statistical tests included a one-way repeated-measures ANOVA, post-hoc two way paired T-tests, statistical power (1-β), correlation (R 2 ), and effect size (Cohen’s d). Results: While statistical significance was not found for changes in SF, SL, or Mean CoPv, small to large effects were found in all measured spatiotemporal parameters of both setups. During Treadmill Walking, vWBV was correlated with a decrease in SF (R 2 = 0.925), an increase in SL (R 2 = 0.908), and an increase in Mean CoPv (R 2 = 0.921) and Max CoPv (R 2 = 0.952) with a significant increase (p < 0.0083) in Max CoPv at frequencies of 8 Hz and higher. Significance: Study results demonstrated that vWBV influences spatiotemporal gait parameters at frequencies greater than previously studied.Istituto Nazionale per l’As­sicurazione contro gli Infortuni sul Lavoro (INAIL

Vibration transmissibility and apparent mass changes from vertical whole-body vibration exposure during stationary and propelled walking

International audienceWhole-Body Vibration (WBV) is an occupational hazard affecting employees working with transportation,construction or heavy machinery. To minimize vibration-induced pathologies, ISO identified WBV exposurelimits based on vibration transmissibility and apparent mass studies. The ISO guidelines do not account forvariations in posture or movement. In our study, we measured the transmissibility and apparent mass at themouth, lower back, and leg of participants during stationary and propelled walking. Stationary walking trans­missibility was significantly higher at the lumbar spine and bite bar at 5 and 10 Hz compared to all higherfrequencies while the distal tibia was lower at 5 Hz compared to 10 and 15 Hz. Propelled walking transmissibilitywas significantly higher at the bite bar and knee at 2 Hz than all higher frequencies. These results vary frompreviously published transmissibility values for static participants, showing that ISO standards should beadjusted for active workers