Effects of Low Dose Caffeine on Post-Exercise Heart Rate Variability: A Double-Blind Placebo-Controlled Trial.

Caffeine may impact post-exercise heart rate variability (HRV); although, studies have yielded inconsistent findings. We examined the effects of low dose caffeine on post-exercise HRV. Healthy, college-aged adults [n = 18; age: 22.1 ± 2.6 years; BMI: 26.9 ± 4.3 kg/m2; estimated maximal oxygen consumption (VO2max): 45.1 ± 8.3 ml·kg-1·min-1] participated in a repeated-measures, double-blind, placebo-controlled trial. During the experimental trials, participants were fitted with a heart rate monitor and a mouthpiece with a one-way nonrebreathing valve and then rested for 10 min during baseline HRV and expired gas assessments. Participants chewed either caffeine (~170mg) or placebo gum for 5 min. Following expectoration and a 5 min warmup, participants walked on a treadmill for 20 min at 60% of estimated VO2max and then rested for 30 min. HRV indices were calculated from 10 min measurements during baseline and post-exercise (post 1, 2, and 3). A main effect of treatment was found for standard deviation of RR intervals (SDNN), absolute power of low frequency band (LF), absolute power of high frequency band (HF), and the standard deviation perpendicular to the line-of-identity in Poincaré plot (SD1) (p < 0.05). Further, a trend for higher root mean square of successive RR interval differences (RMSSD) with caffeine was observed (p = 0.066). Post hoc t-tests revealed that post-exercise SDNN, LF, HF, and SD1 were higher with caffeine compared to placebo (p ≤ 0.012). Results demonstrated that low dose caffeine did not delay the recovery of HRV indices reflective of parasympathetic nervous system activity following an acute bout of moderate exercise.

Antimicrobial and degradable triazolinedione (TAD) crosslinked polypeptide hydrogels.

Hydrogels are perfectly suited to support cell and tissue growth in advanced tissue engineering applications as well as classical wound treatment scenarios. Ideal hydrogel materials for these applications should be easy to produce, biocompatible, resorbable and antimicrobial. Here we report the fabrication of degradable covalent antimicrobial lysine and tryptophan containing copolypeptide hydrogels, whereby the hydrogel properties can be independently modulated by the copolypeptide monomer ratio and chiral composition. Well-defined statistical copolypeptides comprising different overall molecular weights as well as ratios of l- and d-lysine and tryptophan at ratios of 35 : 15, 70 : 30 and 80 : 20 were obtained by N-carboxyanhydride (NCA) polymerisation and subsequently crosslinked by the selective reaction of bifunctional triazolinedione (TAD) with tryptophan. Real-time rheology was used to monitor the crosslinking reaction recording the fastest increase and overall modulus for copolypeptides with the higher tryptophan ratio. Water uptake of cylindrical hydrogel samples was dependent on crosslinking ratio but found independent of chiral composition, while enzymatic degradation proceeded significantly faster for samples containing more l-amino acids. Antimicrobial activity on a range of hydrogels containing different polypeptide chain lengths, lysine/tryptophan composition and l/d enantiomers was tested against reference laboratory strains of Gram-negative Escherichia coli (E. coli; ATCC25922) and Gram-positive, Staphylococcus aureus (S. aureus; ATCC25923). log reductions of 2.8-3.4 were recorded for the most potent hydrogels. In vitro leachable cytotoxicity tests confirmed non-cytotoxicity as per ISO guidelines.

Hierarchical biofabrication of biomimetic collagen-elastin vascular grafts with controllable properties via lyophilisation.

This article describes the development of a hierarchical biofabrication technique suitable to create large but complex structures, such as vascular mimicking grafts, using facile lyophilisation technology amenable to multiple other biomaterial classes. The combination of three fabrication techniques together, namely solvent evaporation, lyophilisation, and crosslinking together allows highly tailorable structures from the microstructure up to the macrostructure, and with the ability to independently crosslink each layer it allows great flexibility to match desired native mechanical properties independently of the micro/macrostructure. We have demonstrated the flexibility of this biofabrication technique by independently optimising each of the layers to create a multi-layered arterial structure with tailored architectural and biophysical/biochemical properties using a collagen-elastin composite. Taken together, the facile biofabrication methodology developed has led to the development of a biomimetic bilayered scaffold suitable for use as a tissue engineered vascular graft (for haemodialysis access or peripheral/coronary bypass), or as an in vitro test platform to examine disease progression, pharmacological toxicity, or cardiovascular medical device testing. STATEMENT OF SIGNIFICANCE: The ability to grow large complex tissues such as blood vessels for transplantation is often hampered by the limitations of the selected biofabrication technique. Here, we sought to overcome some of the fabrication limitations for naturally occurring cardiovascular polymers (collagen/elastin) via a hierarchical approach to fabrication where each layer is built upon the previous. This approach enabled the flexibility to modify and tailor each layer's properties independently via control over polymer concentration, microstructure, and crosslinking. This simple approach facilitated us to fabricate multi-layered vascular grafts which were remodelled into high-density vascular tissue after 21-days. The fabrication approach could be translated to a myriad of other tissues while the engineered vascular graft could also be used as a test platform for drugs/medical devices or as a tissue engineering scaffold for vascular grafting for different indications.

Collagen scaffolds functionalised with copper-eluting bioactive glass reduce infection and enhance osteogenesis and angiogenesis both in vitro and in vivo.

The bone infection osteomyelitis (typically by Staphylococcus aureus) usually requires a multistep procedure of surgical debridement, long-term systemic high-dose antibiotics, and - for larger defects - bone grafting. This, combined with the alarming rise in antibiotic resistance, necessitates development of alternative approaches. Herein, we describe a one-step treatment for osteomyelitis that combines local, controlled release of non-antibiotic antibacterials with a regenerative collagen-based scaffold. To maximise efficacy, we utilised bioactive glass, an established osteoconductive material with immense capacity for bone repair, as a delivery platform for copper ions (proven antibacterial, angiogenic, and osteogenic properties). Multifunctional collagen-copper-doped bioactive glass scaffolds (CuBG-CS) were fabricated with favourable microarchitectural and mechanical properties (up to 1.9-fold increase in compressive modulus over CS) within the ideal range for bone tissue engineering. Scaffolds demonstrated antibacterial activity against Staphylococcus aureus (up to 66% inhibition) whilst also enhancing osteogenesis (up to 3.6-fold increase in calcium deposition) and angiogenesis in vitro. Most significantly, when assessed in a chick embryo in vivo model, CuBG-CS not only demonstrated biocompatibility, but also a significant angiogenic and osteogenic response, consistent with in vitro studies. Collectively, these results indicate that the CuBG-CS developed here show potential as a one-step osteomyelitis treatment: reducing infection, whilst enhancing bone healing.

Macrophage Polarization in Response to Collagen Scaffold Stiffness Is Dependent on Cross-Linking Agent Used To Modulate the Stiffness.

Macrophages are the first responders to biomaterial implantation and determine the success or failure of an implant through their polarization into proinflammatory (M1) and anti-inflammatory (M2) states. It is known that material properties such as stiffness can influence this response, with these properties typically modulated using a cross-linking agent. However, the cellular response comparing different cross-linking agents is often not analyzed. In this study, collagen scaffolds were cross-linked with one physical (DHT) and two chemical cross-linking methods (EDAC and genipin) in order to independently modulate the stiffness of scaffolds. The physical and structural properties of the scaffolds were thoroughly characterized to ensure that macrophage behaviors toward scaffold stiffness and cross-linking agent employed could be evaluated independent of each other. Through gene expression and protein secretion analysis of THP1 cultures, we demonstrate that the macrophage response to collagen scaffold stiffness is dependent on the cross-linking agent used. Macrophages respond similarly to scaffolds of increasing stiffness generated using the same cross-linking agent. However, when exposed to scaffolds of similar bulk modulus and degradation characteristics cross-linked using different cross-linkers, the cells responded to the cross-linking agent used rather than to the bulk modulus of the scaffolds. Moreover, while genipin cross-linking suppressed both proinflammatory and anti-inflammatory responses from macrophages, EDAC cross-linking promoted a robust proinflammatory and anti-inflammatory response to M1 and M2 factors, respectively. The results demonstrate the potential of using tailored individual cross-linking treatments depending on the clinical indication. Taken together, the results from this study highlight the importance of understanding the macrophage response to both chemical and physical properties of scaffolds in order to promote positive remodeling outcomes after biomaterial implantation.

Impact of Genetic Variability on Physiological Responses to Caffeine in Humans: A Systematic Review.

Emerging research has demonstrated that genetic variation may impact physiological responses to caffeine consumption. The purpose of the present review was to systematically recognize how select single nucleotide polymorphisms (SNPs) impact habitual use of caffeine as well as the ergogenic and anxiogenic consequences of caffeine. Two databases (PubMed and EBSCO) were independently searched using the same algorithm. Selected studies involved human participants and met at least one of the following inclusion criteria: (a) genetic analysis of individuals who habitually consume caffeine; (b) genetic analysis of individuals who underwent measurements of physical performance with the consumption of caffeine; (c) genetic analysis of individuals who underwent measurements of mood with the consumption of caffeine. We included 26 studies (10 randomized controlled trials, five controlled trials, seven cross-sectional studies, three single-group interventional studies and one case-control study). Single nucleotide polymorphisms in or near the cytochrome P450 (CYP1A2) and aryl hydrocarbon receptor (AHR) genes were consistently associated with caffeine consumption. Several studies demonstrated that the anxiogenic consequences of caffeine differed across adenosine 2a receptor (ADORA2A) genotypes, and the studies that investigated the effects of genetic variation on the ergogenic benefit of caffeine reported equivocal findings (CYP1A2) or warrant replication (ADORA2A).

Staphylococcal Osteomyelitis: Disease Progression, Treatment Challenges, and Future Directions.

Osteomyelitis is an inflammatory bone disease that is caused by an infecting microorganism and leads to progressive bone destruction and loss. The most common causative species are the usually commensal staphylococci, with Staphylococcus aureus and Staphylococcus epidermidis responsible for the majority of cases. Staphylococcal infections are becoming an increasing global concern, partially due to the resistance mechanisms developed by staphylococci to evade the host immune system and antibiotic treatment. In addition to the ability of staphylococci to withstand treatment, surgical intervention in an effort to remove necrotic and infected bone further exacerbates patient impairment. Despite the advances in current health care, osteomyelitis is now a major clinical challenge, with recurrent and persistent infections occurring in approximately 40% of patients. This review aims to provide information about staphylococcus-induced bone infection, covering the clinical presentation and diagnosis of osteomyelitis, pathophysiology and complications of osteomyelitis, and future avenues that are being explored to treat osteomyelitis.

Introducing a multifaceted exercise intervention particular to older adults diagnosed with Parkinson's disease: a preliminary study.

BACKGROUND AND AIM: With a substantial increase in diagnosed Parkinson's disease, it is of great importance to examine tolerance and physical measures of evolving exercise interventions. Of particular importance, a multifaceted exercise intervention combining active-assisted cycling and resistance training to older adults diagnosed with Parkinson's disease is being assessed. METHODS: Fourteen older adults diagnosed with Parkinson's disease and ten healthy older adults (67.5 ± 7.9 years of age) engaged in an 8-week, 24-session, multifaceted exercise protocol. The protocol consisted of both active-assisted cycling and resistance training. Tolerance was measured, as well as multiple indicators of health-related physical fitness. These indicators examined improvements in cardiovascular performance, muscular strength, muscular endurance, and flexibility. RESULTS: Twenty-two older adults and older adults diagnosed with Parkinson's disease tolerated the intervention by completing all 24 sessions. Repeated-measures analysis of variance demonstrated significant (P ≤ 0.003) improvements in cardiovascular performance, muscular strength, muscular endurance, and flexibility for both groups of individuals. DISCUSSION AND CONCLUSION: The multifaceted intervention is the first to combine both active-assisted cycling and resistance training. The older adult and the older adult diagnosed with Parkinson's disease exhibited both tolerance and health-related improvements in physical fitness following the intervention.