Modifiable traits, healthy behaviours, and leucocyte telomere length

Background: Telomere length is associated with risk of several age-related diseases and cancers. The extent to which telomere length may be modifiable through lifestyle and behaviour and whether this has any clinical consequences is unknown. Methods: In up to 422,797 participants in UK Biobank, we investigated associations of leucocyte telomere length (LTL) with 117 potentially modifiable traits, as well as two indices of healthy behaviours incorporating smoking, physical activity, diet, maintenance of a healthy body weight and alcohol intake. Associations were interpreted as age-related change in LTL by dividing the trait beta coefficients with the age-coefficient. We used Mendelian Randomisation (MR) to test causality of the observed associations of educational attainment and smoking behaviour with LTL. We investigated whether the associations of LTL with 22 diseases were modified by the number of healthy behaviours and the extent to which the associations of more healthy behaviours with greater life expectancy and lower risk of coronary artery disease (CAD) may be mediated through LTL. Results: 71 traits showed significant associations with LTL but most were modest, equivalent to <1 year of age-related change in LTL. In multivariable analyses of 17 traits with stronger associations (equivalent to ≥2 years of age-related change in LTL), five traits (oily fish intake, educational attainment, general health status, walking pace and current smoking) remained significant. MR analysis suggested that educational attainment and smoking behaviour causally affect LTL. Both indices of healthy behaviour were positively and linearly associated with LTL, with those with the healthiest behaviour having longer LTL equivalent to approx. 3.5 years of age-related change in LTL when compared with those with the least heathy behaviours (P<0.001). However, healthy behaviours only explained <0.2% of the total variation in LTL and did not significantly modify the association of LTL with risk of any of the diseases studied. Neither the association of more healthy behaviours on greater life expectancy or lower risk of CAD were substantially mediated through LTL. Conclusions: Several potentially modifiable traits and healthy behaviours have a quantifiable association with LTL, at least some of which are likely to be causal. However, these effects are not of a sufficient magnitude to substantially alter the association between LTL and various diseases or life expectancy.

Fitness benefits of dietary restriction

Dietary restriction (DR) improves survival across a wide range of taxa yet remains poorly understood. The key unresolved question is whether this evolutionarily conserved response to temporary lack of food is adaptive. Recent work suggests that early-life DR reduces survival and reproduction when nutrients subsequently become plentiful, thereby challenging adaptive explanations. A new hypothesis maintains that increased survival under DR results from reduced costs of overfeeding. We tested the adaptive value of DR response in an outbred population of Drosophila melanogaster fruit flies. We found that DR females did not suffer from reduced survival upon subsequent re-feeding and had increased reproduction and mating success compared to their continuously fully fed (FF) counterparts. The increase in post-DR reproductive performance was of sufficient magnitude that females experiencing early-life DR had the same total fecundity as continuously FF individuals. Our results suggest that the DR response is adaptive and increases fitness when temporary food shortages cease.

Assessment of a Rock Pillar Failure by Using Change Detection Analysis and FEM Modelling

In this paper, various methods have been used to control and evaluate engineering difficulties in mining accurately. Different unstable scenarios occurring at the surfaces of underground mine walls, have been identified by comparing 3D terrestrial laser scanning surveys and subsequent point cloud 3D analysis. These techniques, combined with a change detection analysis approach and the integration of rock mechanics’ modelling, represent an asset for the assessment and management of the risk in mining. The change detection analysis can be used as control of mining and industrial processes as well as to identify valid model scenarios for establishing possible failure causes. A pillar spalling failure has been identified in an Italian underground marble quarry and this topic represents the basis of the present paper. A Finite-Element Method was used to verify the occurrence of relatively high-stress concentrations in the pillar. The FEM modelling revealed that stresses in the proximity of the pillar may have sufficient magnitude to induce cracks growth and spalling failure.

Intracycle power and ventilation mode as potential contributors to ventilator-induced lung injury

Background High rates of inflation energy delivery coupled with transpulmonary tidal pressures of sufficient magnitude may augment the risk of damage to vulnerable, stress-focused units within a mechanically heterogeneous lung. Apart from flow amplitude, the clinician-selected flow waveform, a relatively neglected dimension of inflation power, may distribute inflation energy of each inflation cycle non-uniformly among alveoli with different mechanical properties over the domains of time and space. In this initial step in modeling intracycle power distribution, our primary objective was to develop a mathematical model of global intracycle inflation power that uses clinician-measurable inputs to allow comparisons of instantaneous ICP profiles among the flow modes commonly encountered in clinical practice: constant, linearly decelerating, exponentially decelerating (pressure control), and spontaneous (sinusoidal). Methods We first tested the predictions of our mathematical model of passive inflation with the actual physical performance of a mechanical ventilator–lung system that simulated ventilation to three types of patients: normal, severe ARDS, and severe airflow obstruction. After verification, model predictions were then generated for 5000 ‘virtual ARDS patients’. Holding constant the tidal volume and inflation time between modes, the validated model then varied the flow profile and quantitated the resulting intensity and timing of potentially damaging ‘elastic’ energy and intracycle power (pressure–flow product) developed in response to random combinations of machine settings and severity levels for ARDS. Results Our modeling indicates that while the varied flow patterns ultimately deliver similar total amounts of alveolar energy during each breath, they differ profoundly regarding the potentially damaging pattern with which that energy distributes over time during inflation. Pressure control imposed relatively high maximal intracycle power. Conclusions Flow amplitude and waveform may be relatively neglected and modifiable determinants of VILI risk when ventilating ARDS.

Variation in Neonatal Nutrition Practice and Implications: A Survey of Australia and New Zealand Neonatal Units

Background: Significant global variation exists in neonatal nutrition practice, including in assigned milk composition values, donor milk usage, fortification regimens, probiotic choice and in methods used to calculate and report nutrition and growth outcomes, making it difficult to synthesize data to inform evidence-based, standardized nutritional care that has potential to improve neonatal outcomes. The Australasian Neonatal Dietitians' Network (ANDiN) conducted a survey to determine the degree to which neonatal nutritional care varies across Australia and New Zealand (A&amp;NZ) and to highlight potential implications.Materials and Methods: A two-part electronic neonatal nutritional survey was emailed to each ANDiN member (n = 50). Part-One was designed to examine individual dietetic practice; Part-Two examined site-specific nutrition policies and practices. Descriptive statistics were used to examine the distribution of responses.Results: Survey response rate: 88%. Across 24 NICU sites, maximum fluid targets varied (150–180 mL.kg.d−1); macronutrient composition estimates for mothers' own(MOM) and donor (DM) milk varied (Energy (kcal.dL−1) MOM: 65–72; DM 69–72: Protein (g.dL−1): MOM: 1.0–1.5; DM: 0.8–1.3); pasteurized DM or unpasteurized peer-to-peer DM was not available in all units; milk fortification commenced at different rates and volumes; a range of energy values (kcal.g−1) for protein (3.8–4.0), fat (9.0–10.0), and carbohydrate (3.8–4.0) were used to calculate parenteral and enteral intakes; probiotic choice differed; and at least seven different preterm growth charts were employed to monitor growth.Discussion: Our survey identifies variation in preterm nutrition practice across A&amp;NZ of sufficient magnitude to impact nutrition interventions and neonatal outcomes. This presents an opportunity to use the unique skillset of neonatal dietitians to standardize practice, reduce uncertainty of neonatal care and improve the quality of neonatal research.

Дифференциальный фон электрического сигнала, снимаемого с индукционной магнитной головки

Experimental dependences U(t) of the electric voltage taken from an induction magnetic head (MH) moving relative to a magnetic carrier (MH) are presented. The backgrounds of the edges of the MN, local defects of the MN, the background of the inhomogeneous magnetic field of the local source, the backgrounds of defects and structural inhomogeneities of the object, the etheric electromagnetic background, the background of the quality of the surface of the object and surface microscopic inhomogeneities of the material have been identified and investigated. The resonant backgrounds of self-excitation of the measuring system on the signals of the edges of the MN, defects of the MN, instrument and network pickups and interference, object defects, and etheric electromagnetic fields are revealed and investigated. Resonance peaks are the result of self-excitation of the measuring system, which includes the MG, and arise on the trailing edges of any signals of sufficient magnitude, the duration of the trailing edge of which is about a quarter of the period of natural oscillations of the measuring system. The amplitude and frequency spectra of the background signals of object defects, MI and noise and the analytical expressions describing them are determined. The results of the extraction of the useful signal from the complete signal recorded on the MN are shown. Investigations of the differential background of an electric signal allow, together with the previously developed methods of hysteresis interference, to control the properties of objects in an automatic mode with program control, which significantly increases the sensitivity and accuracy of control. To achieve this goal, it is recommended to set the parameters of the measurement system at the threshold of the onset of natural free oscillations in it.

Pathophysiology

Compression neuropathy is the commonest form of peripheral nerve injury and refers to the symptoms and clinicopathological findings that arise when a peripheral nerve is subjected to acute or chronic external compression or impingement of sufficient magnitude to impair its microcirculation. As aerobic glycolysis fails, membrane potential regulation is impaired, and action potential transmission fails. The differential susceptibility of the various fibre types, which subserve different functions, results in a typical progression of symptoms from impaired fine touch and proprioception, through paraesthesia, to poorly localized pain. If compression persists, then secondary intraneural and vascular anatomical changes establish a downward spiral of worsening intraneural oedema and fibrosis, axonotmesis, and denervation atrophy of target muscles. The condition becomes refractory to decompression. The impact on the patient depends upon the severity of neuropathy, and the nerve affected. A small number of anatomical sites particularly predispose to compression (e.g. the carpal tunnel), resulting in the common clinical syndromes.

Intracycle Power and Ventilation Mode as Potential Contributors to Ventilator-Induced Lung Injury

Background: High rates of inflation energy delivery coupled with transpulmonary tidal pressures of sufficient magnitude may augment the risk of damage to vulnerable, stress-focused units within a mechanically heterogeneous lung. Apart from flow amplitude, the clinician-selected flow waveform, a relatively neglected dimension of inflation power, may distribute inflation energy non-uniformly among alveoli with different mechanical properties. Our primary objectives were to develop a mathematical model of intracycle inflation power that allows comparisons among the flow modes commonly encountered in clinical practice: constant, linearly decelerating, exponentially decelerating (pressure control), and spontaneous (sinusoidal).Methods: We first tested the predictions of our mathematical model of passive inflation with the physical performance of a mechanical ventilator-lung system that simulated ventilation to three types of patients: normal, severe ARDS, and severe airflow obstruction. After verification, model predictions were then generated for 5000 ‘virtual ARDS patients’. Holding constant the tidal volume and inflation time between modes, the validated model varied the flow profile and quantitated intensity and timing of potentially damaging ‘elastic’ energy and intracycle power (pressure-flow product) developed in response to random combinations of machine settings and severity levels for ARDS.Results: Our modeling indicates that while the varied flow patterns ultimately deliver similar total amounts of alveolar energy during each breath, they differ profoundly regarding the potentially damaging pattern with which that energy distributes over time during inflation. Pressure control imposed relatively high maximal intracycle power.Conclusions: Flow amplitude and waveform may be relatively neglected and modifiable determinants of VILI risk when ventilating ARDS.

Osteoporosis: A Long-Term and Late-Effect of Breast Cancer Treatments

Osteoporosis is both a long-term effect (occurs during treatment and extends after treatment) and a late-effect (occurs after treatment ends) of breast cancer treatments. The worldwide prevalence of osteoporosis is estimated to be some 200 million patients. About one in three postmenopausal women will experience an osteoporotic (or fragility) fracture of the hip, spine, or wrist. breast cancer treatments, including gonadotropin-releasing hormone (GnRH) agonists, chemotherapy-induced ovarian failure (CIOF), and aromatase inhibitors (AIs), cause bone loss and increase the risks of osteoporosis. Also, breast cancer is a disease of aging, and most of the “one in eight” lifetime risks of breast cancer are in women in their sixth, seventh, and eighth decades. The majority of women diagnosed with breast cancers today will be long-term survivors and experience personal cures. It is the coalescence of osteoporosis with breast cancer, two common and age-related conditions that make osteoporosis relevant in women with breast cancer throughout the continuum from diagnosis, treatment, and survivorship. It is critical to remember that women (and men) will lose bone after age thirty years. However, only certain women will lose bone of sufficient magnitude to merit treatment with anti-osteoporosis drugs. The narrative review is intended for medical, surgical, radiation oncologists, and other mid-level providers, and provides an overview of bone loss and the prevention and treatment of osteoporosis.

A gut-secreted peptide controls arousability through modulation of dopaminergic neurons in the brain

Since sensory information is always present in the environment, animals need to internally regulate their responsiveness to fit the context. During sleep, the threshold for sensory arousal is increased so that only stimuli of sufficient magnitude can cross it. The mechanisms that make arousability flexible are largely mysterious, but they must integrate sensory information with information about physiology. We discovered a gut-to-brain signaling pathway that uses information about ingested nutrients to control arousability from sleep, without affecting sleep duration. Protein ingestion causes endocrine cells in the Drosophila gut to increase production of CCHa1, a peptide that decreases sensory responsiveness. CCHa1 is received by a small group of brain dopaminergic neurons whose activity gates behavioral responsiveness to mechanical stimulation. These dopaminergic neurons innervate the mushroom body, a brain structure involved in determining sleep duration. This work describes how the gut tunes arousability according to nutrient availability, allowing deeper sleep when dietary proteins are abundant. It also suggests that behavioral flexibility is increased through independent tuning of sleep depth and duration.