Elimination of virus-like particles reduces protein aggregation and extends replicative lifespan in Saccharomyces cerevisiae.

A major consequence of aging and stress, in yeast to humans, is an increased accumulation of protein aggregates at distinct sites within the cells. Using genetic screens, immunoelectron microscopy, and three-dimensional modeling in our efforts to elucidate the importance of aggregate annexation, we found that most aggregates in yeast accumulate near the surface of mitochondria. Further, we show that virus-like particles (VLPs), which are part of the retrotransposition cycle of Ty elements, are markedly enriched in these sites of protein aggregation. RNA interference-mediated silencing of Ty expression perturbed aggregate sequestration to mitochondria, reduced overall protein aggregation, mitigated toxicity of a Huntington's disease model, and expanded the replicative lifespan of yeast in a partially Hsp104-dependent manner. The results are in line with recent data demonstrating that VLPs might act as aging factors in mammals, including humans, and extend these findings by linking VLPs to a toxic accumulation of protein aggregates and raising the possibility that they might negatively influence neurological disease progression.

Mechanical and strain behaviour of human Achilles tendon during in vitro testing to failure.

The Achilles tendon is the strongest tendon in the human body but its mechanical behaviour during failure has been little studied and the basis of its high tensile strength has not been elucidated in detail. In the present study, healthy, human, Achilles tendons were loaded to failure in an anatomically authentic fashion while the local deformation and strains were studied in real time, with very high precision, using digital image correlation (DIC). The values determined for the strength of the Achilles tendon were at the high end of those reported in the literature, consistent with the absence of a pre-existing tendinopathy in the samples, as determined by careful gross inspection and histology. Early in the loading cycle, the proximal region of the tendon accumulated high lateral strains while longitudinal strains remained low. However, immediately before rupture, the mid-substance of the Achilles tendon, its weakest part, started to show high longitudinal strains. These new insights advance the understanding of the mechanical behaviour of tendons as they are stretched to failure.

The role of the posterior bundle of the medial collateral ligament in posteromedial rotatory instability of the elbow.

Aims: The aim of this study was to evaluate two hypotheses. First, that disruption of posterior bundle of the medial collateral ligament (PMCL) has to occur for the elbow to subluxate in cases of posteromedial rotatory instability (PMRI) and second, that ulnohumeral contact pressures increase after disruption of the PMCL. Materials and Methods: Six human cadaveric elbows were prepared on a custom-designed apparatus which allowed muscle loading and passive elbow motion under gravitational varus. Joint contact pressures were measured sequentially in the intact elbow (INTACT), followed by an anteromedial subtype two coronoid fracture (COR), a lateral collateral ligament (LCL) tear (COR + LCL), and a PMCL tear (COR + LCL + PMCL). Results: There was no subluxation or joint incongruity in the INTACT, COR, and COR + LCL specimens. All specimens in the COR + LCL + PMCL group subluxated under gravity-varus loads. The mean articular contact pressure of the COR + LCL group was significantly higher than those in the INTACT and the COR groups. The mean articular contact pressure of the COR + LCL + PMCL group was significantly higher than that of the INTACT group, but not higher than that of the COR + LCL group. Conclusion: In the presence of an anteromedial fracture and disruption of the LCL, the posterior bundle of the MCL has to be disrupted for gross subluxation of the elbow to occur. However, elevated joint contact pressures are seen after an anteromedial fracture and LCL disruption even in the absence of such subluxation. Cite this article: Bone Joint J 2018;100-B:1060-5.

Nematic structuring of transparent and multifunctional nanocellulose papers.

The nematic structuring of cellulose nanofibers (CNFs) is proposed as a nanostructural engineering tool for exploiting the potential of CNFs in conceptually new "transparent papers". The nematic-structured CNF papers exhibit superior mechanical properties, optical transparency, gas-barrier properties, heat transfer properties and electrical resistivity, compared with conventional randomly-structured CNF papers.

Overall and peripheral lung function assessment by spirometry and forced oscillation technique in relation to asthma diagnosis and control.

BACKGROUND: Classic spirometry is effort dependent and of limited value in assessing small airways. Peripheral airway involvement, and relation to poor control, in asthma, has been highlighted recently. Forced oscillation technique (FOT) offers an effort-independent assessment of overall and peripheral lung mechanics. We studied the association between lung function variables, obtained either by spirometry or multifrequency (5, 11 and 19 Hz) FOT, and asthma diagnosis and control. METHODS: Spirometry measures, resistance at 5 (R5) and 19 Hz (R19), reactance at 5 Hz (X5), resonant frequency (fres ), resistance difference between 5-19 Hz (R5-R19) and Asthma Control Test scores were determined in 234 asthmatic and 60 healthy subjects (aged 13-39 years). We used standardized lung function variables in logistic regression analyses, unadjusted and adjusted for age, height, gender and weight. RESULTS: Lower FEV1 /FVC (OR [95% CI] 0.47 [0.32, 0.69]) and FEF50 (0.62 [0.46, 0.85]) per standard deviation increase, and higher R5 (3.31 [1.95, 5.62]) and R19 (2.54 [1.65, 3.91]) were associated with asthma diagnosis. Independent predictive effects of FEV1 /FVC and R5 or R19, respectively, were found for asthma diagnosis. Lower FEV1 /FVC and altered peripheral FOT measures (X5, fres and R5-R19) were associated with uncontrolled asthma (P-values < .05). CONCLUSIONS: Resistance FOT measures were equally informative as spirometry, related to asthma diagnosis, and, furthermore, offered additive information to FEV1 /FVC, supporting a complementary role for FOT. Asthma control was related to FOT measures of peripheral airways, suggesting a potential use in identifying such involvement. Further studies are needed to determine a clinical value and relevant reference values in children, for the multifrequency FOT measurements.

Oriented clay nanopaper from biobased components--mechanisms for superior fire protection properties.

The toxicity of the most efficient fire retardant additives is a major problem for polymeric materials. Cellulose nanofiber (CNF)/clay nanocomposites, with unique brick-and-mortar structure and prepared by simple filtration, are characterized from the morphological point of view by scanning electron microscopy and X-ray diffraction. These nanocomposites have superior fire protection properties to other clay nanocomposites and fiber composites. The corresponding mechanisms are evaluated in terms of flammability (reaction to a flame) and cone calorimetry (exposure to heat flux). These two tests provide a wide spectrum characterization of fire protection properties in CNF/montmorrilonite (MTM) materials. The morphology of the collected residues after flammability testing is investigated. In addition, thermal and thermo-oxidative stability are evaluated by thermogravimetric analyses performed in inert (nitrogen) and oxidative (air) atmospheres. Physical and chemical mechanisms are identified and related to the unique nanostructure and its low thermal conductivity, high gas barrier properties and CNF/MTM interactions for char formation.

Which set of embryo variables is most predictive for live birth? A prospective study in 6252 single embryo transfers to construct an embryo score for the ranking and selection of embryos.

STUDY QUESTION: Which embryo score variables are most powerful for predicting live birth after single embryo transfer (SET) at the early cleavage stage? SUMMARY ANSWER: This large prospective study of visual embryo scoring variables shows that blastomere number (BL), the proportion of mononucleated blastomeres (NU) and the degree of fragmentation (FR) have independent prognostic power to predict live birth. WHAT IS KNOWN ALREADY: Other studies suggest prognostic power, at least univariately and for implantation potential, for all five variables. A previous study from the same centre on double embryo transfers with implantation as the end-point resulted in the integrated morphology cleavage (IMC) score, which incorporates BL, NU and EQ. STUDY DESIGN, SIZE AND DURATION: A prospective cohort study of IVF/ICSI SET on Day 2 (n = 6252) during a 6-year period (2006-2012). The five variables (BL NU, FR, EQ and symmetry of cleavage (SY)) were scored in 3- to 5-step scales and subsequently related to clinical pregnancy and LBR. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 4304 women undergoing IVF/ICSI in a university-affiliated private fertility clinic were included. Generalized estimating equation models evaluated live birth (yes/no) as primary outcome using the embryo variables as predictors. Odds ratios with 95% confidence intervals and P-values were presented for each predictor. The C statistic (i.e. area under receiver operating characteristic curve) was calculated for each model. Model calibration was assessed with the Hosmer-Lemeshow test. A shrinkage method was applied to remove bias in c statistics due to over-fitting. MAIN RESULTS AND THE ROLE OF CHANCE: LBR was 27.1% (1693/6252). BL, NU, FR and EQ were univariately highly significantly associated with LBR. In a multivariate model, BL, NU and FR were independently significant, with c statistic 0.579 (age-adjusted c statistic 0.637). EQ did not retain significance in the multivariate model. Prediction model calibration was good for both pregnancy and live birth. We present a ranking tree with combinations of values of the BL, NU and FR embryo variables for optimal selection of the embryo/s to transfer, providing a revised IMC score. The five embryo variables had similar effects over all age groups. LIMITATIONS, REASONS FOR CAUTION: Limitations of the present study are those inherent for real-time visual scoring, including risks of inter-observer variation and the hazards of fixed time-point scoring procedures in a dynamic process. The study is restricted to Day-2 transfers. WIDER IMPLICATIONS OF THE FINDINGS: To our knowledge this is the largest prospective, SET study performed with the explicit aim of constructing an evidence-based embryo score for the ranking and selection of early cleavage stage embryos. In line with previous research, our data suggest that the symmetry of cleavage variable may be omitted when scoring embryos in the early cleavage stage. We suggest that, following validation in other populations, the revised IMC score may be used when international standards for embryo scoring are discussed. STUDY FUNDING/COMPETING INTEREST: Carl von Linné Clinic, Uppsala and the Department of Women's and Children's Health and the Family Planning Fund in Uppsala, Uppsala University, Uppsala, Sweden financed this study. There are no competing interests to declare.

Analysis of intraosseous samples in endotoxemic shock--an experimental study in the anaesthetised pig.

BACKGROUND: Intraosseous (IO) access is used in emergency situations to allow rapid initiation of treatment. IO access is also sometimes used for blood sampling, although data on accuracy of such sampling in critical illness are limited. There is also a potential risk that bone marrow fragments in IO samples may damage laboratory equipment. It is ethically questionable to perform a simultaneous comparison between IO and arterial/venous sampling in critically ill humans. We have, thus, studied the analytical performance of IO sampling in a porcine septic shock model using a cartridge-based analyser. METHODS: Eight pigs with endotoxin-induced septic shock were sampled hourly for 6 h, and analysed for blood gases, acid base status, haemoglobin, glucose and lactate using point of care instruments. Samples were taken from three IO cannulae (tibia bilaterally, one with infusion, and humerus), one arterial and one venous. An interaction test was used to assess changes in agreement between methods over time. Bland­Altman plots were constructed to study bias between methods. RESULTS: There were, to a varying extent, differences between IO and arterial/venous levels for all studied variables, but agreement did not change significantly during the experiment. A general finding was a large dispersion of differences between methods. CONCLUSIONS: IO sample values should be treated with caution in this setting but may add useful information to the clinical picture. The tibia or humerus may be used for sampling. IO infusion decreases agreement, thus sampling during infusion should be avoided.

Expected and experienced pain during epidural catheter insertion.

BACKGROUND: Insertion of an epidural catheter for pain relief is frequently used in anaesthetic practice. Little is known regarding patients' expected vs. experienced pain and discomfort due to the epidural block procedure. The purpose of this study was to investigate the expected and experienced pain, respectively, associated with the epidural procedure in patients undergoing major abdominal surgery. METHODS: Thirty adult, unselected patients scheduled for elective major abdominal surgery were included in this study, which was approved by the ethics committee. Pre-operative insertion of an epidural catheter had to be a part of the anaesthetic routine procedure. Immediately before the epidural procedure, the patients were asked to grade the pain they expected from the procedure on an 11-point numeric rating system scale, ranging from 0 to 10, where '0' is no pain and '10' is worst imaginable pain. When the procedure had been carried out, the patients were once again asked to grade how much pain they had experienced. RESULTS: The median expected pain as a result of the epidural procedure was 5.0. Median experienced pain was 2.0. The median difference between the expected and experienced pain was -3.0 (P < 0.0001). The only patient who expected less pain than she subsequently experienced had a paraesthetic sensation. Gender, age, or previous experience from central neuraxial block did not significantly affect neither expected nor experienced pain. CONCLUSIONS: Patients expect significantly more pain than they experience from receiving an epidural block.

Cellulose nanocrystals/polyurethane nanocomposites. Study from the viewpoint of microphase separated structure.

Cellulose nanocrystals (CNC) successfully obtained from microcrystalline cellulose (MCC) were dispersed in a thermoplastic polyurethane as matrix. Nanocomposites containing 1.5, 5, 10 and 30 wt% CNC were prepared by solvent casting procedure and properties of the resulting films were evaluated from the viewpoint of polyurethane microphase separated structure, soft and hard domains. CNC were effectively dispersed in the segmented thermoplastic elastomeric polyurethane (STPUE) matrix due to the favorable matrix-nanocrystals interactions through hydrogen bonding. Cellulose nanocrystals interacted with both soft and hard segments, enhancing stiffness and stability versus temperature of the nanocomposites. Thermal and mechanical properties of STPUE/CNC nanocomposites have been associated to the generated morphologies investigated by AFM images.

Consumption of fructose-sweetened beverages for 10 weeks reduces net fat oxidation and energy expenditure in overweight/obese men and women.

BACKGROUND/OBJECTIVES: The results of short-term studies in humans suggest that, compared with glucose, acute consumption of fructose leads to increased postprandial energy expenditure and carbohydrate oxidation and decreased postprandial fat oxidation. The objective of this study was to determine the potential effects of increased fructose consumption compared with isocaloric glucose consumption on substrate utilization and energy expenditure following sustained consumption and under energy-balanced conditions. SUBJECTS/METHODS: As part of a parallel arm study, overweight/obese male and female subjects, 40-72 years, consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Energy expenditure and substrate utilization were assessed using indirect calorimetry at baseline and during the 10th week of intervention. RESULTS: Consumption of fructose, but not glucose, led to significant decreases of net postprandial fat oxidation and significant increases of net postprandial carbohydrate oxidation (P<0.0001 for both). Resting energy expenditure (REE) decreased significantly from baseline values in subjects consuming fructose (P=0.031) but not in those consuming glucose. CONCLUSIONS: Increased consumption of fructose for 10 weeks leads to marked changes of postprandial substrate utilization including a significant reduction of net fat oxidation. In addition, we report that REE is reduced compared with baseline values in subjects consuming fructose-sweetened beverages for 10 weeks.

Biomechanical comparison of three fixation techniques used for four-corner arthrodesis.

Clinical results following four-corner arthrodesis vary and suggest that nonunion may be related to certain fixation techniques. The purpose of our study was to examine the displacement between the lunate and capitate following a simulated four-corner arthrodesis with the hypothesis that three types of fixation (Kirschner wires, dorsal circular plate, and a locked dorsal circular plate) would allow different amounts of displacement during simulated wrist flexion and extension. Cadaver wrists with simulated four-corner arthrodeses were loaded cyclically either to implant failure or until the lunocapitate displacement exceeded 1 mm. The locked dorsal circular plate group was significantly more stable than the dorsal circular plate and K-wire groups (p = 0.018 and p = 0.006). While these locked dorsal circular plates appear to be very stable our results are limited only to the biomechanical behavior of these fixation techniques within a cadaver model.

Adipositas athletica: a group of neglected conditions associated with medical risks.

At the 2008 Olympics, the body weight of the athletes varied from 28 to 181 kg and many Olympic athletes therefore today have a stature far from the ancient Greek athletic ideals. Athletes and sports associated with leanness and their medical problems have been researched extensively. However, there has been less focus on those athletes, who may gain a competitive advantage by having excess body fat, being large or oversized. The present review introduces for the first time the concept of Adipositas athletica and gives a description and classification of these athletes. Adipositas athletica is defined as having a higher than "athletic normal" (Greek Olympic ideals) fat mass and being an elite athlete. The condition is divided into subgroups based on the intent or non-intent to increase body fat per se. Another factor is the intent to increase body mass as well as increasing physiological factors such as strength or endurance. It is concluded that most of the sports-medicine community-physicians, researchers and nutritionists - has neglected these oversized and obese athletes, their long- and short-term morbidity and mortality, their eating problems and the use of performance-enhancing drugs. Although some data on overweight and obese athletes exist, the most remarkable finding when reviewing the literature is the paucity of data. Many unanswered questions remain and great strides remain to be made.

Replacing dairy fat with rapeseed oil causes rapid improvement of hyperlipidaemia: a randomized controlled study.

BACKGROUND: Rapeseed oil (RO), also known as canola oil, principally contains the unsaturated fatty acids 18:1n-9, 18:2n-6 and 18:3n-3 and may promote cardiometabolic health. OBJECTIVE: To investigate the effects on lipoprotein profile, factors of coagulation and insulin sensitivity of replacing a diet rich in saturated fat from dairy foods (DF diet) with a diet including RO-based fat (RO diet). DESIGN: During a 2×3-week randomized, controlled, cross-over trial, 20 free-living hyperlipidaemic subjects were provided with isocaloric test diets that differed in fat composition alone. Blood lipoprotein profile, coagulation and fibrinolytic factors and insulin sensitivity (euglycaemic clamp) were determined before and after the dietary intervention. RESULTS: All subjects completed the study, and compliance was high according to changes in serum fatty acids. The RO diet, but not the DF diet, reduced the levels of serum cholesterol (-17%), triglycerides (-20%) and low-density lipoprotein cholesterol (-17%), cholesterol/high-density lipoprotein (HDL) cholesterol ratio (-21%), apolipoprotein (apo) B/apo A-I ratio (-4%) and factor VII coagulant activity (FVIIc) (-5%) from baseline. These changes were significantly different between the diets (P=0.05 to P<0.0001), except for FVIIc (P=0.1). The RO diet, but not the DF diet, modestly increased serum lipoprotein(a) (+6%) and tended to increase the glucose disappearance rate (K-value, +33%). HDL cholesterol, insulin sensitivity, fibrinogen and tissue plasminogen activator inhibitor-1 levels did not change from baseline or differ between the two diets. CONCLUSIONS: In a diet moderately high in total fat, replacing dairy fat with RO causes a rapid and clinically relevant improvement in serum lipoprotein profile including lowering of triglycerides in hyperlipidaemic individuals.

Sagittal abdominal diameter as a screening tool in clinical research: cutoffs for cardiometabolic risk.

Background. Waist girth and BMI are commonly used as markers of cardiometabolic risk. Accumulating data however suggest that sagittal abdominal diameter (SAD) or "abdominal height" may be a better marker of intra-abdominal adiposity and cardiometabolic risk. We aimed to identify cutoffs for SAD using a cardiometabolic risk score. Design. A population-based cross-sectional study. Methods. In 4032 subjects (1936 men and 2096 women) at age 60, different anthropometric variables (SAD, BMI, waist girth, and waist-to-hip ratio) were measured and cardiometabolic risk score calculated. ROC curves were used to assess cutoffs. Results. Among men SAD showed the strongest correlations to the majority of the individual risk factors; whereas in women SAD was equal to that of waist girth. In the whole sample, the area under the ROC curve was highest for SAD. The optimal SAD cutoff for an elevated cardiometabolic risk score in men was approximately 22 cm (95%CI; 21.6 to 22.8) and in women approximately 20 cm (95%CI; 19.4 to 20.8). These cutoffs were similar if the Framingham risk score was used. Conclusions. These cutoffs may be used in research and screening to identify "metabolically obese" men who would benefit from lifestyle and pharmacological interventions. These results need to be verified in younger age groups.

Making flexible magnetic aerogels and stiff magnetic nanopaper using cellulose nanofibrils as templates.

Nanostructured biological materials inspire the creation of materials with tunable mechanical properties. Strong cellulose nanofibrils derived from bacteria or wood can form ductile or tough networks that are suitable as functional materials. Here, we show that freeze-dried bacterial cellulose nanofibril aerogels can be used as templates for making lightweight porous magnetic aerogels, which can be compacted into a stiff magnetic nanopaper. The 20-70-nm-thick cellulose nanofibrils act as templates for the non-agglomerated growth of ferromagnetic cobalt ferrite nanoparticles (diameter, 40-120 nm). Unlike solvent-swollen gels and ferrogels, our magnetic aerogel is dry, lightweight, porous (98%), flexible, and can be actuated by a small household magnet. Moreover, it can absorb water and release it upon compression. Owing to their flexibility, high porosity and surface area, these aerogels are expected to be useful in microfluidics devices and as electronic actuators.

A dynamic method for in vitro multisegment spine testing.

Robotics recently spread to spine biomechanical research. The aim of the present work is to describe and validate a new method for in vitro studying of a multisegmental spinal specimen under dynamic conditions. This method relies on the use of a simulator with six degrees of freedom (to impose movements in all directions), an optoelectric apparatus (for collecting kinematics data) and an original system for attaching kinematic markers, allowing their precise removal and replacement under different examination conditions. The accuracy of measurements as well as their reproducibility under static and dynamic conditions is reported here in the study of a human lumbar spinal specimen (L1-sacrum). The method appears to be reliable and reproducible, and should therefore enable future studies of variations in mobility between healthy and pathological spines, to better understand the influence of different implants on spinal kinematics.

The effect of radioscapholunate fusion on wrist movement and the subsequent effects of distal scaphoidectomy and triquetrectomy.

Radioscapholunate arthrodesis is a salvage procedure indicated for osteoarthritis of the radiocarpal joint involving the lunate facet of the radius. This cadaver study examines changes in wrist motion resulting from radioscapholunate arthrodesis, and the effects of surgical techniques to improve the range of motion. Simulated radioscapholunate arthrodesis, distal scaphoidectomy and triquetrectomy were carried out sequentially on six cadaver forearms and measurements (maximum flexion/extension and radial/ulnar deviation) were taken in the intact situation and after each surgical step using a magnetic tracking device. Radioscapholunate arthrodesis diminishes the amplitudes of movements of the wrist in all directions, but range of motion in the radioscapholunate fused wrist improves after scaphoidectomy and improves further after triquetrectomy (88% of original flexion/extension and 98% of original radial/ulnar deviation). Radioscapholunate arthrodesis causes a significant change in kinematics between the hamate and the triquetrum in flexion/extension.

Invariant natural killer (iNK) T cell deficiency in patients with common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a B cell immunodeficiency disorder characterized frequently by failure of memory B cell development and antibody secretion. A unifying cellular pathogenesis for CVID has not been forthcoming, but given the immunoregulatory role of invariant NK (iNK) T cells and their absence in several other immunodeficiencies, we quantified these cells in the blood of 58 CVID patients. There was a marked decrease in the proportion of iNK T cells in CVID patients compared with controls. This was particularly notable in those with low isotype-switched memory B cells, but subset analysis demonstrated no difference when stratified by specific clinical features. We propose that the decreased proportion of iNK T cells in CVID might be linked to the failure of memory B cell generation, which may contribute to reduced antibody production in these patients.