Tuning the critical gelation temperature of thermo-responsive diblock copolymer worm gels

Amphiphilic diblock copolymer nano-objects can be readily prepared using reversible addition–fragmentation chain transfer (RAFT) polymerization. For example, poly(glycerol monomethacrylate) (PGMA) chain transfer agents (CTA) can be chain-extended using 2-hydroxypropyl methacrylate (HPMA) via RAFT aqueous dispersion polymerization to form well-defined spheres, worms or vesicles at up to 25% solids. The worm morphology is of particular interest, since multiple inter-worm contacts lead to the formation of soft free-standing gels, which undergo reversible degelation on cooling to sub-ambient temperatures. However, the critical gelation temperature (CGT) for such thermo-responsive gels is ≤20 °C, which is relatively low for certain biomedical applications. In this work, a series of new amphiphilic diblock copolymers are prepared in which the core-forming block comprises a statistical mixture of HPMA and di(ethylene glycol) methyl ether methacrylate (DEGMA), which is a more hydrophilic monomer than HPMA. Statistical copolymerizations proceeded to high conversion and low polydispersities were achieved in all cases (Mw/Mn < 1.20). The resulting PGMA-P(HPMA-stat-DEGMA) diblock copolymers undergo polymerization-induced self-assembly at 10% w/w solids to form free-standing worm gels. SAXS studies indicate that reversible (de)gelation occurs below the CGT as a result of a worm-to-sphere transition, with further cooling to 5 °C affording weakly interacting copolymer chains with a mean aggregation number of approximately four. This corresponds to almost molecular dissolution of the copolymer spheres. The CGT can be readily tuned by varying the mean degree of polymerization and the DEGMA content of the core-forming statistical block. For example, a CGT of 31 °C was obtained for PGMA59-P(HPMA91-stat-DEGMA39). This is sufficiently close to physiological temperature (37 °C) to suggest that these new copolymer gels may offer biomedical applications as readily-sterilizable scaffolds for mammalian cells, since facile cell harvesting can be achieved after a single thermal cycle

SLC37A1 and SLC37A2 Are Phosphate-Linked, Glucose-6-Phosphate Antiporters

Blood glucose homeostasis between meals depends upon production of glucose within the endoplasmic reticulum (ER) of the liver and kidney by hydrolysis of glucose-6-phosphate (G6P) into glucose and phosphate (Pi). This reaction depends on coupling the G6P transporter (G6PT) with glucose-6-phosphatase-α (G6Pase-α). Only one G6PT, also known as SLC37A4, has been characterized, and it acts as a Pi-linked G6P antiporter. The other three SLC37 family members, predicted to be sugar-phosphate:Pi exchangers, have not been characterized functionally. Using reconstituted proteoliposomes, we examine the antiporter activity of the other SLC37 members along with their ability to couple with G6Pase-α. G6PT- and mock-proteoliposomes are used as positive and negative controls, respectively. We show that SLC37A1 and SLC37A2 are ER-associated, Pi-linked antiporters, that can transport G6P. Unlike G6PT, neither is sensitive to chlorogenic acid, a competitive inhibitor of physiological ER G6P transport, and neither couples to G6Pase-α. We conclude that three of the four SLC37 family members are functional sugar-phosphate antiporters. However, only G6PT/SLC37A4 matches the characteristics of the physiological ER G6P transporter, suggesting the other SLC37 proteins have roles independent of blood glucose homeostasis

A proposal for the evaluation of the bioeconomic efficiency of beef cattle production systems

ABSTRACT The objective of this study was to identify types of production system and their main indicators on bioeconomic efficiency, using qualitative and quantitative methods to evaluate beef cattle farms in the western region of the state of Rio Grande do Sul. A survey was carried out with 43 farmers operating in the western region of that state. All farms operated with complete cycle production systems in areas larger or equal to 900 ha. A qualitative questionnaire with binary answers and a quantitative questionnaire with numerical answers were applied. Technology and Management drivers were used for the calculation of the efficiency index of farmers obtained by both questionnaires. Farmers were divided into three clusters: low-efficiency level (LEL), intermediate-efficiency level (IEM), or high-efficiency level (HEL), as a result of the comparison of the scores obtained for the analyzed parameters. Subfactors resulting from each comparison (LEL × IEL; LEL × HEL, and IEL × HEL) were different as a function of the comparison and of the methods applied. Low-efficiency level farmers need to improve essential production processes, such as technology and management, as well as health management practices together with the financial management of the production system. Intermediate-efficiency level farmers need to improve their routine animal management, pasture management, and calculation of financial indicators to become highly efficient. The quantitative method allowed to identify underestimation (39.3%) or overestimation (24.2%) when farmers were are classified in clusters. Different methods may be used, but those based on quantitative information have stronger discrimination power to identify different types of farmers

Ventilation and outcomes following robotic-assisted abdominal surgery: an international, multicentre observational study

Background: International data on the epidemiology, ventilation practice, and outcomes in patients undergoing abdominal robotic-assisted surgery (RAS) are lacking. The aim of the study was to assess the incidence of postoperative pulmonary complications (PPCs), and to describe ventilator management after abdominal RAS. Methods: This was an international, multicentre, prospective study in 34 centres in nine countries. Patients ≥18 yr of age undergoing abdominal RAS were enrolled between April 2017 and March 2019. The Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score was used to stratify for higher risk of PPCs (≥26). The primary outcome was the incidence of PPCs. Secondary endpoints included the preoperative risk for PPCs and ventilator management. Results: Of 1167 subjects screened, 905 abdominal RAS patients were included. Overall, 590 (65.2%) patients were at increased risk for PPCs. Meanwhile, 172 (19%) patients sustained PPCs, which occurred more frequently in 132 (22.4%) patients at increased risk, compared with 40 (12.7%) patients at lower risk of PPCs (absolute risk difference: 12.2% [95% confidence intervals (CI), 6.8–17.6%]; P&lt;0.001). Plateau and driving pressures were higher in patients at increased risk, compared with patients at low risk of PPCs, but no ventilatory variables were independently associated with increased occurrence of PPCs. Development of PPCs was associated with a longer hospital stay. Conclusions: One in five patients developed one or more PPCs (chiefly unplanned oxygen requirement), which was associated with a longer hospital stay. No ventilatory variables were independently associated with PPCs. Clinical trial registration: NCT02989415

Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: A review

The leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) has been extensively used as an ergogenic aid; particularly among bodybuilders and strength/power athletes, who use it to promote exercise performance and skeletal muscle hypertrophy. While numerous studies have supported the efficacy of HMB in exercise and clinical conditions, there have been a number of conflicting results. Therefore, the first purpose of this paper will be to provide an in depth and objective analysis of HMB research. Special care is taken to present critical details of each study in an attempt to both examine the effectiveness of HMB as well as explain possible reasons for conflicting results seen in the literature. Within this analysis, moderator variables such as age, training experience, various states of muscle catabolism, and optimal dosages of HMB are discussed. The validity of dependent measurements, clustering of data, and a conflict of interest bias will also be analyzed. A second purpose of this paper is to provide a comprehensive discussion on possible mechanisms, which HMB may operate through. Currently, the most readily discussed mechanism has been attributed to HMB as a precursor to the rate limiting enzyme to cholesterol synthesis HMG-coenzyme A reductase. However, an increase in research has been directed towards possible proteolytic pathways HMB may operate through. Evidence from cachectic cancer studies suggests that HMB may inhibit the ubiquitin-proteasome proteolytic pathway responsible for the specific degradation of intracellular proteins. HMB may also directly stimulate protein synthesis, through an mTOR dependent mechanism. Finally, special care has been taken to provide future research implications

Cross Adaptation - Heat and Cold Adaptation to Improve Physiological and Cellular Responses to Hypoxia

To prepare for extremes of heat, cold or low partial pressures of O2, humans can undertake a period of acclimation or acclimatization to induce environment specific adaptations e.g. heat acclimation (HA), cold acclimation (CA), or altitude training. Whilst these strategies are effective, they are not always feasible, due to logistical impracticalities. Cross adaptation is a term used to describe the phenomenon whereby alternative environmental interventions e.g. HA, or CA, may be a beneficial alternative to altitude interventions, providing physiological stress and inducing adaptations observable at altitude. HA can attenuate physiological strain at rest and during moderate intensity exercise at altitude via adaptations allied to improved oxygen delivery to metabolically active tissue, likely following increases in plasma volume and reductions in body temperature. CA appears to improve physiological responses to altitude by attenuating the autonomic response to altitude. While no cross acclimation-derived exercise performance/capacity data have been measured following CA, post-HA improvements in performance underpinned by aerobic metabolism, and therefore dependent on oxygen delivery at altitude, are likely. At a cellular level, heat shock protein responses to altitude are attenuated by prior HA suggesting that an attenuation of the cellular stress response and therefore a reduced disruption to homeostasis at altitude has occurred. This process is known as cross tolerance. The effects of CA on markers of cross tolerance is an area requiring further investigation. Because much of the evidence relating to cross adaptation to altitude has examined the benefits at moderate to high altitudes, future research examining responses at lower altitudes should be conducted given that these environments are more frequently visited by athletes and workers. Mechanistic work to identify the specific physiological and cellular pathways responsible for cross adaptation between heat and altitude, and between cold and altitude, is warranted, as is exploration of benefits across different populations and physical activity profiles