35%Co-20%Cr-35%Ni-10%Mo alloy (MP35N) with a low titanium (LT) content is commonly used as the material for the manufacture of leads in medical applications such as Cardiac Rhythmic Management (CRM), neurostimulation and Deep Brain Stimulation (DBS). The material is drawn to thin wires, and this involves subjecting the material to extensive plastic deformation to obtain the desired mechanical and fatigue properties. The critical part in the medical device design requires understanding the relationship between the processing method, microstructure and their impact on the cyclic performance. In this study, the influence of drawing practices namely Full Die Drawing (FDD) and Half Die Drawing (HDD) on the cyclic performance of MP35NLT wires have been investigated, by differing the amount of plastic strain applied on the material. The as-drawn wires were subjected to rotary beam fatigue tests (R = -1) with varying stress amplitudes, and the microstructural factors controlling the Low Cycle Fatigue (LCF) and High Cycle Fatigue (HCF) performance were determined through post fatigued TEM investigations. The results conclude that there is a significant impact on the drawing techniques on the fatigue performance of MP35NLT wires, with the FDD wires having a higher endurance limit than the HDD drawn wire until 75% CW, but there was a slight drop in the fatigue performance when the CW was increased to 95%. This was attributed to the difference in grain sizes, dislocation structures, twin density, twin spacing, and grain boundary orientations observed between the two wires which contributed to contrasting cyclic behavior. The drop-in fatigue performance of the FDD wire upon an increased strain to 95% has been attributed to the shear band formations in the material, which increased the stress localization in the material bestowing to drop-in fatigue performance.

Turbine blisk low cycle fatigue (LCF) is affected by various factors such as heat load, structural load, operation parameters and material parameters; it seriously influences the reliability and performance of the blisk and aeroengine. To study the influence of thermal-structural coupling on the reliability of blisk LCF life, the generalized regression extreme neural network (GRENN) method was proposed by integrating the basic thoughts of generalized regression neural network (GRNN) and the extreme response surface method (ERSM). The mathematical model of the developed GRENN method was first established in respect of the LCF life model and the ERSM model. The method and procedure for reliability and sensitivity analysis based on the GRENN model were discussed. Next, the reliability and sensitivity analyses of blisk LCF life were performed utilizing the GRENN method under a thermal-structural interaction by regarding the randomness of gas temperature, rotation speed, material parameters, LCF performance parameters and the minimum fatigue life point of the objective of study. The analytical results reveal that the reliability degree was 0.99848 and the fatigue life is 9419 cycles for blisk LCF life when the allowable value is 6000 cycles so that the blisk has some life margin relative to 4500 cycles in the deterministic analysis. In comparison with ERSM, the computing time and precision of the proposed GRENN under 10,000 simulations is 1.311 s and 99.95%. This is improved by 15.18% in computational efficiency and 1.39% in accuracy, respectively. Moreover, high efficiency and high precision of the developed GRENN become more obvious with the increasing number of simulations. In light of the sensitivity analysis, the fatigue ductility index and temperature are the key factors of determining blisk LCF life because their effect probabilities reach 41% and 26%, respectively. Material density, rotor speed, the fatigue ductility coefficient, the fatigue strength coefficient and the fatigue ductility index are also significant parameters for LCF life. Poisson's ratio and elastic modulus of materials have little effect. The efforts of this paper validate the feasibility and validity of GRENN in the reliability analysis of blisk LCF life and give the influence degrees of various random parameters on blisk LCF life, which are promising to provide useful insights for the probabilistic optimization of turbine blisk LCF life.

In this study, 16Mo3 steel was analysed for fatigue tests under tension-compression and oscillatory bending conditions. The analysis involved a comparison of fatigue test results obtained using the Manson-Coffin-Basquin, Langer and Kandil models and the models proposed by Kurek-Łagoda. It was observed that it is possible to substitute the basic tension-compression test performed in large testing machines with oscillatory bending tests carried out on a simple, modern test stand. The tests were performed under oscillatory bending on a prototype machine. The testing of 16Mo3 steel proved that the best-known Mason-Coffin-Basquin fatigue characteristic describes the results of all of the experimental tests very well, but the model can only be used when it is possible to divide strains into elastic and plastic components. It should be emphasised here that there is no such possibility in the case of tests performed under oscillatory bending conditions. It was proven that the proposed test method can substitute the tension-compression test very well and be a much more cost efficient way to obtain LCF material fatigue properties.

Forming technology and in particular cold forward rod extrusion is one of the key manufacturing technologies with regard to the production of shafts. The selection of process parameters determines the global and local material properties. This particularly implies forming-induced initial damage in representation of pores. On this background, this study aims on describing the influence of these pores in the performance of the material 16MnCrS5 (DIN 1.7139, AISI/SAE 5115) under a torsional load path in the low cycle fatigue regime, which is highly relevant for shafts under operation conditions. For this purpose, the method of cyclic forward-reverse torsional testing was applied. Additionally, intermittent testing method and the characterization of the state of crack growth using selective electron microscopy analysis of the surface were combined. A first attempt was made to describe the influence of forming-induced initial damage on the fatigue performance and the crack growth mechanisms. The correlation of fatigue performance and initial damage was contiguous in the sense that the initial damage corresponds with a decrease of material performance. It was concluded that the focus of further investigations must be on small crack growth and the related material changes to identify the role of initial damage under cyclic loads.

Keywords: AISI/SAE 5115); case hardening steel 16MnCrS5 (DIN 1.7139; forming-induced initial damage; low cycle fatigue performance; torsional load paths.

The effect of low cycle fatigue (LCF) predamage on the subsequent very high cycle fatigue (VHCF) behavior is investigated in TC21 titanium alloy. LCF predamage is applied under 1.8% strain amplitude up to various fractions of the expected life and subsequent VHCF properties are determined using ultrasonic fatigue tests. Results show that 5% of predamage insignificantly affects the VHCF limit due to the absence of precrack, but decreases the subsequent fatigue crack initiation life estimated by the Pairs law. Precracks introduced by 10% and 20% of predamage significantly reduce the subsequent VHCF limits. The crack initiation site shifts from subsurface-induced fracture for undamaged and 5% predamaged specimens to surface precrack for 10% and 20% predamaged specimens in very high cycle region. Furthermore, the predicted fatigue limits based on the El Haddad modified model for the predamaged specimens agree with the experimental results.

La(1-x)Ca(x)FeO3 (X = 0.0, 0.2, 0.4, abbreviated as LCF) as cathode material for intermediate temperature solid oxide fuel cells (IT-SOFC) was synthesized by new route of glycine nitrate method. LCF materials were characterized by X-ray diffraction (XRD), scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDX), transmission electron microscopy (TEM), electrical and electrochemical impedance spectroscopy (EIS). The powder LCFs exhibited single phase with orthorhombic structure, highly porous and small nanoparticles with average size of 200-300 nm. The electrical conductivities of LCFs increased as increasing the Ca content and achieved the maximum electrical conductivity of 148 Scm(-1) for La0.6Ca0.4FeO3 (X = 0.4) at 550 degrees C. The improved conductivity of LCFs could be a promising cathode material for IT-SOFCs. In the impedance analysis of fabricated symmetry cell with the optimized La0.6Ca0.4FeO3 cathode and Ce0.8Sm0.2O3 (SDC) electrolyte, the minimum area specific resistance (ASR) of 0.15 omegacm2 was observed at 850 degrees C, which may due to the lowest activation energy (1.55 eV), resulting from the reduction of oxygen molecules into oxygen ions. It was found that calcium doping was essential to increase the charge carrier concentration of lanthanum iron oxide materials, resulting in the high conductivity at intermediate temperature.

OBJECTIVE

To understand the extent of the alcohol industry's financial dependence on drinking above government low-risk guidelines in England.

METHODS

Scenario modelling using descriptive analyses of pooled data from the 2013 and 2014 waves of two nationally representative surveys: the Health Survey for England (HSE) and the Living Costs and Food Survey (LCF). We estimated the proportion of alcohol sales revenue accounted for by drinkers above guideline levels, and how this varies between different beverage and retailer types. We then estimated the impact on sales revenue if the entire population reduced their drinking to within guideline levels, as well as the average price increases necessary to compensate for such a loss of revenue.

METHODS

England.

METHODS

A total of 16 872 individual (HSE) and 9975 household (LCF) survey respondents.

METHODS

Transaction-level estimates of volume of alcohol purchased and price paid by beverage type and trade sector.

RESULTS

Those drinking above guideline levels are estimated to account for 68% of total alcohol sales revenue in 2013/14: 81% of off-trade revenue and 60% of on-trade revenue. This represents 77% of beer, 70% of cider, 66% of wine and 50% of spirits sales value. The heaviest drinking 4% of the population account for 30% of all consumption and 23% of all industry revenue. If all consumers reduced their drinking to within guideline levels, alcohol sales revenue could decline by 38% (£13 billion). To mitigate this loss, average prices paid would have to rise substantially-for example, by £2.64 for a pint of on-trade beer or £12.25 for a 70 cl bottle of off-trade spirits.

CONCLUSIONS

In England, the alcohol industry appears to be highly financially dependent upon heavy drinking, and might face significant financial losses were consumers to drink within guideline levels.

Presently, the discovery of effective drugs and pesticides from eco-friendly biological sources is an important challenge in the field of life sciences. The present research was aimed for standardizing an innovative approach in the evaluation of the biological potentiality of the metabolites of fish-associated bacteria. We have identified 17 skin-associated bacteria from the freshwater fish, giant danio, Devario aquipinnatus. They were screened through biofilm forming and extracellular enzyme producing ability. The results of preliminary antibacterial evaluation of the bacterial supernatants underlined the importance of three potential strains (BH8, BH10 and BH11) for further applied research. Hence, such strains were subsequently subjected to a novel extraction procedure to overcome the difficulties found in polar solvents mixed with the supernatant. The lyophilized cell-free supernatant (LCFS) of 3 isolates were individually extracted by using methanol. During the testing of LCFS's methanolic extract (LCFS-ME) of 3 isolates, only the extract of BH11-strain exhibited potent inhibitory activity against the pathogenic bacteria and fungi. Furthermore, the larvicidal and mosquitocidal assays on the filariasis vector, Culex quinquefasciatus also showed its potent toxicity on both the adults and developmental instars of mosquito. Through molecular and phylogenetic analyses, the BH11 strain was identified as Salmonella bongori (KR350635). The present finding emphasized that the S. bongori could be an important novel source of effective antimicrobials and mosquitocidal agents.

The objectives of this study were to determine if there was variation in atrazine tolerance, measured by intensity of leaf-disc chlorophyll fluorescence, in triazine-resistant and -susceptible Brassica napus in terms of age of leaf on the plant, time of day, and time of assay after leaf disc removal and immersion in atrazine. In a growth room and field experiment, triazine-susceptible B. napus cv. "Tower" and triazine-resistant B. napus cv. "OAC Triton" were used. Chlorophyll fluorescence intensity measurements were made 15-30 min after disc removal. In both environments, two periods of reduced photosynthetic efficiency occurred in the circadian phase. The times that these periods occurred during the diurnal phase differed between biotypes. A phase shift in leaf chlorophyll fluorescence (LCF) maxima between resistant and susceptible biotypes resulted in two periods, early and late in the light phase, of increased LCF in resistant tissue. This differential pattern in LCF is support for the hypothesis that triazine-resistance chloroplast alterations imply an alteration in the temporal organization of chloroplast physiological function. Atrazine reduced the photosynthetic efficiency of resistant tissue in some instances. This could indicate that triazine resistance is not complete and that some metabolic role may be involved. The results reported here indicate that the most accurate estimation of the physiological state will be obtained from LCF measurements taken soon after leaf disc removal from the plant.

The purpose of this study was to determine how tibiofemoral joint compressive forces and knee joint-spanning muscle forces during uphill walking change compared to level walking in patients with total knee arthroplasty (TKA). A musculoskeletal model capable of resolving total (TCF), medial (MCF), and lateral (LCF) tibiofemoral compressive forces was used to determine compressive forces and muscle forces during level and uphill walking on a 10° incline for twenty-five post TKA patients. A 2?2 (slope: level and 10° ? limb: replaced and non-replaced) repeated measures ANOVA was used to detect differences in knee contact forces between slope and limb conditions and their interaction. Peak loading-response TCF, MCF, and LCF were greater during uphill walking than level walking for non-replaced limbs. During uphill walking, peak loading-response TCF was smaller in the replaced limb compared to non-replaced limbs with no change in MCF or LCF. Peak knee extension moment and knee extensor muscle force were smaller in replaced limbs compared to non-replaced limbs during uphill walking. During level walking, replaced and non-replaced limbs experienced rather equal joint loading, however replaced limb experienced reduced joint loading during uphill walking. Differences in joint loading between replaced and non-replaced limbs were not present during level walking, suggesting compensation from the replaced limb during the more difficult task. Uphill walking following TKA promotes more balanced loading of replaced limbs during stance, however these benefits may come at the expense of increased loading on non-replaced limbs.

Background: Long Chai Fang (LCF) is a traditional Chinese medicine (TCM) formula for treating chronic hepatitis B (CHB) in clinical settings; however, its related mechanism remains unclear.

Methods: To address this issue, network pharmacology and an integrative method that combines dot-blot hybridization and metabolomics analysis were employed. Network pharmacology was performed to investigate the material basis and potential mechanisms of LCF against CHB. The effect of LCF on Duck hepatitis B virus (DHBV) replication was evaluated. The metabolomics analysis was conducted to identify potential biomarkers in duck serum.

Results: The network pharmacology approach revealed 133 potential active components, 897 drug targets, 979 disease targets, and 185 drug-disease targets, while the Kyoto Encyclopedia of Genes and Genomes enrichment analysis identified 165 pathways. LCF significantly inhibited DHBV-deoxyribonucleic acid replication on day 10 and day 3 after the cessation of treatment. Notably, the low-dose LCF group showed the best inhibitory effect. The obviously sustained anti-DHBV activity of LCF inhibited viral replication, and a rebound reaction was found. Phosphatidylcholine and phosphatidylethanolamine classes, which are mainly involved in liver cell repair and energy metabolism through phospholipid metabolic pathways, were identified by metabolomics analysis.

Conclusions: our results showed that the main active ingredients of LCF appear to be metacarpi, isorhamnetin, glypallichalcone, and phaseolinisoflavan. This study provides novel strategies for using a LCF formula against CHB in future research.

Keywords: Duck hepatitis B virus (DHBV); Long Chai Fang (LCF); chronic hepatitis B (CHB); metabolomics analysis; network pharmacology.

Aims: Gender disparities exist in smoking-related lung cancer epidemiology, but the molecular basis has not been explored so far. We aimed at identifying genes with gender-bias expression pattern in smoking lung cancer patients for understanding the molecular basis of gender bias in smokers using meta-analysis of microarray gene expression data.

Materials and methods: Transcriptome of around 1100 samples from 13 studies were used in the meta-analysis to identify 'Lung Cancer genes specific to Female-Smokers' (LCFS) and 'Lung Cancer genes specific to Male-Smokers' (LCMS). The expression profiles of these genes were validated with an independent microarray report and TCGA-RNA-sequencing data. The molecular interactions, pathway, and other functional annotations were portrayed for the key genes identified.

Key findings: We identified 1159 gender-biased genes in smoking lung cancer patients. Of these, 400 and 474 genes showed differential expression in cancerous compared to normal lung of women (LCFS) and men (LCMS), respectively. While many up-regulated LCFS were involved in 'immune responses' including T-cell activation, leukocyte cell-cell adhesion, the LCMS were mainly involved in 'positive regulation of gene expression', signaling pathways including RAS, VEGF, insulin-receptor signaling, and 'cell cycle'.

Significance: The strategic-method identified genes, particularly, SNX20, GIMAP6, MTMR2, FAM171B, IDH1, MOBP, FBXO17, LPXN and WIPF1, which were consistently differentially expressed in at least 4 studies, and in agreement with RNA-Seq data. Exploring their functions could be beneficial to the gender-based diagnosis, prognosis, and treatment of lung cancer in smokers. The current meta-analysis supports existing knowledge of sexual-dimorphism of immune responses in cancer.

Keywords: Gender-bias; Gene expression meta-analysis; Lung cancer; NSCLC; Precision medicine; Smokers.

The results of comprehensive studies on accelerated (artificial) ageing and biodegradation of polymer biocomposites on PBS matrix filled with raw wheat bran (WB) are presented in this paper. These polymer biocomposites are intended for the manufacture of goods, in particular disposable packaging and disposable utensils, which decompose naturally under the influence of biological agents. The effects of wheat bran content within the range of 10-50 wt.% and extruder screw speed of 50-200 min^-1 during the production of biocomposite pellets on the resistance of the products to physical, chemical, and biological factors were evaluated. The research included the determination of the effect of artificial ageing on the changes of structural and thermal properties by infrared spectra (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TG). They showed structural changes-disruption of chains within the ester bond, which occurred in the composition with 50% bran content as early as after 250 h of accelerated ageing. An increase in the degree of crystallinity with ageing was also found to be as high as 48% in the composition with 10% bran content. The temperature taken at the beginning of weight loss of the compositions studied was also lowered, even by 30 °C at the highest bran content. The changes of mechanical properties of biocomposite samples were also investigated. These include: hardness, surface roughness, transverse shrinkage, weight loss, and optical properties: colour and gloss. The ageing hardness of the biocomposite increased by up to 12%, and the surface roughness (R_a) increased by as much as 2.4 µm at the highest bran content. It was also found that ageing causes significant colour changes of the biocomposition (ΔE = 7.8 already at 10% bran content), and that the ageing-induced weight loss of the biocomposition of 0.31-0.59% is lower than that of the samples produced from PBS alone (1.06%). On the other hand, the transverse shrinkage of moldings as a result of ageing turned out to be relatively small, at 0.05%-0.35%. The chemical resistance of biocomposites to NaOH and HCl as well as absorption of polar and non-polar liquids (oil and water) were also determined. Biodegradation studies were carried out under controlled conditions in compost and weight loss of the tested compositions was determined. The weight of samples made from PBS alone after 70 days of composting decreased only by 4.5%, while the biocomposition with 10% bran content decreased by 15.1%, and with 50% bran, by as much as 68.3%. The measurements carried out showed a significant influence of the content of the applied lignocellulosic fillers (LCF) in the form of raw wheat bran (WB) on the examined properties of the biocompositions and the course of their artificial ageing and biodegradation. Within the range under study, the screw speed of the extruder during the production of biocomposite pellets did not show any significant influence on most of the studied properties of the injection mouldings produced from it.

Keywords: accelerated ageing; agro-flour filler; agro-waste materials; biofiller; biopolymer; composites; discolouration; lignocellulosic materials; natural filler; thermal properties; thermal resistance.

Background: Segmental cervical instability is a risk factor for the progression of osteophytic bone spurs and development of myelopathy, and is treated as a relative contraindication of cervical laminoplasty. The aim of this study was to compare laminoplasty with selective fixation (LPSF) versus laminectomy with fusion (LCF) in patients with multilevel cervical myelopathy accompanied by segmental instability.

Methods: A case-control study was conducted by reviewing data from 63 patients who underwent LPSF (n = 30) or LCF (n = 33). Cervical alignment, range of motion (ROM), neurologic status and axial symptom severity pre-operation, 3-days after operation, and at the final follow-up (minimum 24 months) were measured and compared between groups.

Results: Postoperation, patients in the LPSF group lost 31.1 ± 17.3 % of cervical lordosis and 43.2 ± 10.9 % cervical ROM while patients in the LCF group lost 5.7 ± 8.2 % and 67.9 ± 15.5 %, respectively. Both LPSF and LCF groups significantly improved neurologic status and axial symptom severity at the final follow-up with similar between-group results(P > 0.05). Blood loss, operation time, hospital stay, and medical cost in the LPSF group were significantly less than in the LCF group(P < 0.05).

Conclusions: In 2 years of clinical observation, LPSF was effective in maintaining the stability of the cervical spine with less sacrifice of mobility and surgical trauma for multilevel myelopathy with segmental instability compared to LCF.

Keywords: Laminectomy and fusion; Laminoplasty; Myelopathy; Segmental instability; Selective fusion.

Background: The study performed to compare the efficacy and safety during radiofrequency ablation (RFA) using ThermoCool SmartTouch and ThermoCool SmartTouch-SF catheters in porcine heart.

Methods and results: RFA was performed on porcine myocardium by using two irrigated ablation catheters. 3 groups were divided based on the different contact force (CF): low contact force (LCF) (1-3g), medium contact force (MCF) (5-10g), and high contact force (HCF) (15-20g). In each group, RFA was delivered at 4 power settings of 30, 40, 50, 60W. At each power, RFA was applied to reach target ablation index (AI) of 350, 450 and 500. Altogether, 360 RF lesions were created by using 72 ablation conditions. AI value was positively correlated with lesion size using ST and STSF catheters. At fixed power, lesion dimensions significantly smaller in LCF group, whereas did not differ between MCF and HCF groups. Furthermore, at fixed CF, lesion dimensions increased with power set at 40W compared with 30W but decreased with high-power RF energy (50W and 60W). Although average lesion surface diameter, maximum diameter were increased using STSF catheter, there were no significant differences in lesion volume between two catheters. The steam pop provoked more frequently using ST catheter, and showed negatively correlated with CF and positively correlated with high-power energy.

Conclusion: STSF catheter is safer and equally effective in lesion formation compared with ST catheter. Lesion volume was increased along with the early increase of CF and power, whereas further increase of CF and power significantly reduces the lesion size. This article is protected by copyright. All rights reserved.

Keywords: AI; catheter; lesion formation; porcine heart; radiofrequency ablation.

The aim of this study was to evaluate the effect of lipid digestion on the permeability and absorption of orally administered saquinavir (SQV), a biopharmaceutics classification system (BCS) class IV drug, in different lipid-based formulations. Three LBFs were prepared: a mixed short- and medium-chain lipid-based formulation (SMCF), a medium-chain lipid-based formulation (MCF), and a long-chain lipid-based formulation (LCF). SQV was loaded into these LBFs at 26.7 mg/g. To evaluate the pharmacokinetics of SQV in vivo, drug-loaded formulations were predispersed in purified water at 3% w/w and orally administered to rats. A low dose (0.8 mg/rat) was employed to limit confounding effects on drug solubilization, and consistent with this design, presolubilization of SQV in the LBFs did not increase in vivo exposure compared to a control suspension formulation. The areas under the plasma concentration-time curve were, however, significantly lower after administration of SQV as MCF and LCF compared to SMCF. To evaluate the key mechanisms underpinning absorption, each LBF containing SQV was digested, and the flux of SQV from the digests across a dialysis membrane was evaluated in in vitro permeation experiments. This study revealed that the absorption profiles were driven by the free concentration of SQV and that this varied due to differences in SQV solubilization in the digestion products generated by LBF digestion. The apparent first-order permeation rate constants of SQV (k_app,total) were estimated by dividing the flux of SQV in the dialysis membrane experiments by the concentration of total SQV on the donor side. k_app,total values strongly correlated with in vivo AUC. The data provide one of the first studies of the effect of digestion products on the free concentration of a drug in the GI fluid and oral absorption. This simple permeation model may be a useful tool for the evaluation of the impact of lipid digestion on apparent drug permeability from lipid-based formulations. These effects should be assessed alongside, and in addition to, the more well-known effects of lipids on enhancing intestinal solubilization of poorly water-soluble drugs.

Keywords: fatty acids; free concentration; in vitro digestion; lipid-based formulation; oral absorption.

Objectives: Deterioration of lip function in the elderly is a form of oral hypofunction. It is important to understand age-related changes in lip function to improve oral health. This study aimed to quantitatively compare the maximum lip-closing force (LCF) and the ability to control LCF during voluntary lip-pursing movements between elderly and young adults and clarify the influence of aging on both measurements.

Methods: Using a multidirectional LCF measurement system, we measured six-directional maximum LCFs (upper, upper right, lower right, lower, lower left, upper right) of 20 healthy elderly men (69.6 ± 4.2 years) and 20 healthy young men (25.1 ± 3.8 years). The ability to control the LCF in each direction was assessed based on the accuracy rate. The directional LCF and the ability to control LCF were compared between the elderly and young adults.

Results: The maximum directional LCF in the elderly adults was significantly smaller than that in the young adults in three directions from the lower lip; moreover, the accuracy rate of the elderly adults was significantly lower than that of young adults in five of the six directions.

Conclusions: Our findings suggest that the influence of aging on the accuracy of LCF may be different from that on muscle strength. Hypofunction of the lips due to aging may result not only from decreased muscle strength but also from reduced LCF accuracy.

Keywords: aging; controlled movement; lip purse; lip-closing force; men; visual feedback.

Standards for the fatigue testing of wearable sensing technologies are lacking. The majority of published fatigue tests for wearable sensors are performed on proof-of-concept stretch sensors fabricated from a variety of materials. Due to their flexibility and stretchability, polymers are often used in the fabrication of wearable sensors. Other materials, including textiles, carbon nanotubes, graphene, and conductive metals or inks, may be used in conjunction with polymers to fabricate wearable sensors. Depending on the combination of the materials used, the fatigue behaviors of wearable sensors can vary. Additionally, fatigue testing methodologies for the sensors also vary, with most tests focusing only on the low-cycle fatigue (LCF) regime, and few sensors are cycled until failure or runout are achieved. Fatigue life predictions of wearable sensors are also lacking. These issues make direct comparisons of wearable sensors difficult. To facilitate direct comparisons of wearable sensors and to move proof-of-concept sensors from "bench to bedside", fatigue testing standards should be established. Further, both high-cycle fatigue (HCF) and failure data are needed to determine the appropriateness in the use, modification, development, and validation of fatigue life prediction models and to further the understanding of how cracks initiate and propagate in wearable sensing technologies.

Keywords: cyclic softening; cyclic testing; fatigue testing; fatigue testing standards; high-cycle fatigue; hysteresis; lead failure; low-cycle fatigue; stretch sensor; wearables.

Study question: Do fetuses from frozen embryo transfer (FET) present signs of cardiac remodeling and suboptimal function similar to those observed in fetuses from fresh embryo transfer (ET)?

Summary answer: Fetuses from both fresh ET and FET present signs of fetal cardiac remodeling and suboptimal function, with more pronounced changes after fresh ET as compared to FET.

What is known already: Our group and others have previously demonstrated that fetuses and children conceived by ARTs present cardiac remodeling and suboptimal function. These fetuses show dilated atria, more globular and thicker ventricles, reduced longitudinal motion, and impaired relaxation. Cardiac changes were already present in utero and persisted after birth. Most of the ART fetuses included in previous publications were from fresh ET. However, singletons from FET have different perinatal outcomes compared to those from fresh ET. There are no previous studies comparing cardiac morphology and function between fetuses following fresh and FET.

Study design, size, duration: This is a prospective cohort study of 300 singleton pregnancies recruited from 2017 to 2020, including 100 spontaneously conceived (SC) pregnancies, 100 fetuses conceived by IVF with FET, and 100 fetuses conceived by IVF with fresh ET. Fetal structural and functional echocardiography was performed in all pregnancies.

Participants/materials, setting, methods: Pregnancies conceived by IVF were recruited from a single assisted reproduction center, ensuring homogeneity in IVF stimulation protocols, endometrial preparation for FET, laboratory procedures, and embryo culture conditions. SC pregnancies from fertile couples were selected from the general population and matched to IVF pregnancies by maternal age. Epidemiological and perinatal outcomes were collected in all cases. Fetal echocardiography was performed at 28-33 weeks of pregnancy to assess cardiac structure and function in all pregnancies. All echocardiographic comparisons were adjusted by maternal age, nulliparity, birthweight centile, preeclampsia, and prematurity.

Main results and the role of chance: Parental age, ethnicity, body mass index and smoking were similar among the study groups. Median gestational age at echocardiography and estimated fetal weight were similar in all study groups. Both fresh ET and FET groups showed similar fetal echocardiographic changes, with more pronounced features in the fresh ET as compared to FET pregnancies. Fetuses conceived by IVF showed larger atria (right atria-to-heart ratio: fresh ET mean 18.1% (SD 3.2) vs FET 18.0% (3.9) vs SC 17.3% (3.2); linear tendency P-value <0.001), more globular ventricles (right ventricular sphericity index: fresh ET 1.62 (0.29) vs FET 1.61 (0.25) vs SC 1.68 (0.26); <0.001) and thicker myocardial walls (relative wall thickness: fresh ET 0.79 (0.21) vs FET 0.74 (0.22) vs SC 0.65 (0.25); <0.001) as compared to SC pregnancies. Both fresh ET and FET groups also had signs of suboptimal systolic and diastolic function, with reduced tricuspid annular systolic peak velocity (fresh ET 7.17 cm/s (1.22) vs FET 7.41 cm/s (1.19) vs SC 7.58 cm/s (1.32); <0.001) and increased left myocardial performance index (fresh ET 0.53 (0.08) vs FET 0.53 (0.08) vs SC 0.50 (0.09); <0.001) as compared to SC pregnancies.

Limitations, reasons for caution: The cardiac changes reported here are subclinical, with most cardiovascular indexes lying within normal ranges. Although echocardiographic changes are recognized as potential cardiovascular risk factors, their association with the long-term cardiovascular disease remains to be proven. The observed milder fetal cardiac features in FET fetuses cannot condition the choice of this technique and must be considered together with the global perinatal results related to these gestations.

Wider implications of the findings: The identification of cardiac remodeling in fetuses conceived by IVF with fresh ET and FET represents an opportunity for early detection. Future studies are warranted to study the potential long-term consequences of these findings.

Study funding/competing interest(s): This project has been partially funded with support from the Erasmus + Programme of the European Union (Framework Agreement number: 2013-0040). This publication reflects the views only of the author, and the Commission cannot be held responsible for any use, which may be made of the information contained therein. Additionally, the research leading to these results has received funding from 'la Caixa' Foundation under grant agreement LCF/PR/GN18/10310003, the Instituto de Salud Carlos III (PI15/00130, PI17/00675, PI18/00073) integrated into the Plan Nacional de I + D+I and cofinanced by ISCIII-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER) 'Una manera de hacer Europa', Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK) and AGAUR 2017 SGR grant n° 1531. The authors declare no conflicts of interest.

Trial registration number: N/A.

Keywords: IVF; cardiac remodeling; fetal heart; frozen embryo transfer; pregnancy.

Background: Muscle weakness negatively affects perioral muscles and quality of life. The button-pull exercise is used to teach lip closure (LC) and to strengthen muscles. However, how the muscles accomplish LC during button-pull and its training effect on each muscle are unknown.

Objectives: This study aimed to investigate the LC mechanism and the efficacy of perioral muscle training.

Methods: Electromyographic (EMG) activities were obtained from perioral muscles along with the lip closing force (LCF) and were normalised to the maximum LC activities. Correlations between muscle activities and LCF were assessed during LCF increment/decrement task. The effectiveness of training methods was evaluated during functional face tasks (FFT). The effects of button-pull on muscles were evaluated during static loadings with two sized buttons.

Results: The muscles were active during LC, and the amplitudes changed with the LCF. In FFT, the muscles were simultaneously active and the total activity was highest during the blowing task. In button-pull, maximum button-pulling forces (BPFs) were significantly larger with the large button (p = .0001). In the static loading task, muscle activities increased with increasing button load. However, the small button produced significantly greater EMG activity than the large button in most of the load (p < .005).

Conclusion: LC is accomplished by the cooperation of perioral muscles. In button-pull, a larger button requires a larger BPF, but a smaller button shows higher muscle activities. Face expression exercises compare favourably with button-pull. Forceful LC and blowing tasks may be effective and balanced training of the perioral muscles.

Keywords: button-pull exercise; electromyography; facial expression; lip closure; perioral muscles.

The aim of this study was to investigate the effect of two dietary treatments (liquid creep feed (LCF) and dry creep feed (DCF)) offered during the suckling period on feed disappearance, number of eaters, and intestinal enzymatic development at weaning in an on-farm study with 347 piglets. Piglets were allocated to either the DCF or LCF treatment from day 10 to day 24 postpartum for 9 h a day. Red ferric oxide (1%) was added to the diet to categorize piglets into eating categories (good eaters, moderate eaters, or non-eaters) via faecal swabs. At weaning, 40 piglets were sampled for intestinal enzymatic development. The LCF treatment increased the dry matter disappearance from day 10-18 (p < 0.001). The percentage of good eaters, moderate eaters and non-eaters did not differ between treatments (p > 0.05). The DCF pigs displayed greater average daily gain (ADG) pre-weaning (p = 0.024), and a greater body weight (BW) at day 61 (p < 0.001). The activity of lactase, maltase and sucrase in the proximal part of the small intestine were greatest (p < 0.001) in the DCF pigs.

Keywords: dry creep feed; eaters and non-eaters; enzyme activity; feed intake; liquid creep feed.

The aim of the study was to test whether logistic curve fitting (LCF) of Turns = f(Amplitude) plots of single muscle contractions can provide a reliable alternative method for peak-ratio calculation. EMG signals from 74 biceps and 62 triceps contractions were analyzed by applying LCF to Turns = f(Amplitude) plots. Peak-ratio (peak-ratio2) could then be calculated as the point of the fitted line with the highest Turn/Amplitude value. LCF yielded R² values > 0.95 in the vast majority of contractions studied (68/74 biceps and 53/62 triceps). Peak-ratio2 values had a very strong linear relationship with the corresponding values calculated by the traditional method (peak-ratio1) in both normal and neurogenic conditions. Furthermore, ROC curve analysis showed that peak-ratio1 and peak-ratio2 had similar AUC values. Based on the LCF equation, peak-ratio = T2*(p - 1)/A0*p*(p - 1)^1/p. Therefore, peak-ratio is proportional to the maximum number of turns (T2), positively correlated to the rate of turns' increment at the midpoint of the curve (p) and negatively correlated to the mean amplitude at the midpoint of the curve (A0). A0 is the variable that best discriminates between normal and neurogenic conditions. We provide an alternative method for peak-ratio calculation and show the variables that influence this sensitive marker of neurogenic disease.

Keywords: Electromyography; Interference; Peak ratio; Turn Amplitude analysis.

Background: Activation of the endocannabinoid system (ECS) is associated with the development of obesity and insulin resistance, and with perturbed skeletal muscle development. Age-related sarcopenia is a progressive and generalized skeletal muscle disorder involving an accelerated loss of muscle mass and function, with changes in skeletal muscle protein homeostasis due to lipid accumulation and anabolic resistance. Hence, both obesity and sarcopenia share a common set of pathophysiological alterations leading to skeletal muscle impairment. The aim of this study was to characterize how sarcopenia impacts the ECS and if these modifications were related to the loss of muscle mass and function associated with aging in rats.

Methods: Six-month-old and 24-month-old male rats were used to measure the contractile properties of the plantarflexors (isometric torque-frequency relationship & concentric power-velocity relationship) and to evaluate locomotor activity, motor coordination, and voluntary gait by open field, rotarod, and catwalk tests, respectively. Levels of endocannabinoids (AEA & 2-AG) and endocannabinoid-like molecules (OEA & PEA) were measured by LCF-MS/MS in plasma, skeletal muscle, and adipose tissue, while the expression of genes coding for the ECS were investigated by quantitative reverse transcription PCR (RT-qPCR).

Results: Sarcopenia in old rats was exemplified by a 49% decrease in hindlimb muscle mass (P < 0.01), which was associated with severe impairment of isometric torque, power, voluntary locomotor activity, motor coordination, and gait quality. Sarcopenia was associated with (1) increased 2-AG (+32%, P = 0.07) and reduced PEA and OEA levels in the plasma (-25% and -40%, respectively, P < 0.01); (2) an increased content of AEA, PEA, and OEA in subcutaneous adipose tissue (P < 0.01); and (3) a four-fold increase of 2-AG content in the soleus (P < 0.01) and a reduced OEA content in EDL (-80%, P < 0.01). These alterations were associated with profound modifications in the expression of the ECS genes in the adipose tissue and skeletal muscle.

Conclusions: Taken together, these findings demonstrate that circulating and peripheral tissue endocannabinoid tone are altered in sarcopenia. They also demonstrate that OEA plasma levels are associated with skeletal muscle function and loss of locomotor activity in rats, suggesting OEA could be used as a circulating biomarker for sarcopenia.

Keywords: Endocannabinoids; Muscle function; Sarcopenia; Skeletal muscle.

Background: Probiotics can release bioactive substances known as postbiotics, which can inhibit pathogenic microorganisms, improve immunomodulation, reduce antioxidant production, and modulate the gut microbiota.

Methods: In this study, we evaluated the in vitro antimicrobial effects, antioxidant activity, and anti-inflammatory potential of 10 lyophilized cell-free supernatants (LCFS) of Lactobacillus isolates. LCFS was obtained via centrifugation and subsequent lyophilization of the supernatant collected from the culture medium ofeach isolate. The antibacterial and antibiofilm activities of the LCFS were determined using broth microdilution. The antioxidant potential was evaluated by measuring the total phenolic and flavonoid contents and 2,2-Diphennyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS⁺) radical scavenging activities.

Results: All the isolates were able to inhibit the four tested pathogens. The isolates exhibited strong antibiofilm activity and eradicated the biofilms formed by Acinetobacter buamannii and Escherichia coli. All the prepared Lactobacillus LCFS contained phenols and flavonoids and exhibited antioxidant activities in the DPPH and ABTS⁺ radical scavenging assays. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay revealed that LCFS was not cytotoxic to RAW 264.7 cells. In addition, the ten Lactobacillus LCFS decreased the production of nitric oxide.

Conclusions: All the isolates have beneficial properties. This research sheds light on the role of postbiotics in functional fermented foods and pharmaceutical products. Further research to elucidate the precise molecular mechanisms of action of probiotics is warranted.

Keywords: Anti-inflammatory; Antibiofilm; Antioxidant; Cell-free supernatants; Lactobacillus; Postbiotics.