Effects of Coffee and Caffeine Anhydrous Intake During Creatine Loading

The purpose of this study was to determine the effect of 5 d of creatine (CRE) loading alone or in combination with caffeine anhydrous (CAF) or coffee (COF) on upper and lower body strength and sprint performance. Physically active males (n=54; Mean ± SD; Age = 20.1 ± 2.1 yrs; Weight = 78.8 ± 8.8 kg) completed baseline testing, consisting of one-repetition maximum (1RM) and repetitions to fatigue (RTF) with 80% 1RM for bench press (BP) and leg press (LP), followed by a repeated sprint test of five, 10 s sprints separated by 60 s rest on a cycle ergometer to determine peak power (PP) and total power (TP). At least 72 hr later, subjects were randomly assigned to supplement with CRE (5 g creatine monohydrate, 4 times*d−1; n=14), CRE+CAF (CRE + 300 mg*d−1 of CAF; n=13), CRE+COF (CRE + 8.9 g COF, yielding 303 mg caffeine; n=13), or placebo (PLA; n=14) for 5 d. Serum creatinine (CRN) was measured prior to and following supplementation and on day six, participants repeated pre-testing procedures. Strength measures were improved in all groups (p<0.05), with no significant time × treatment interactions. No significant interaction or main effects were observed for PP. For TP, a time × sprint interaction was observed (p<0.05), with no significant interactions between treatment groups. A time × treatment interaction was observed for serum CRN values (p<0.05) that showed increases in all groups except PLA. Four subjects reported mild gastrointestinal discomfort with CRE+CAF, with no side effects reported in other groups. These findings suggest that neither CRE alone, nor in combination with CAF or COF, significantly affected performance compared to PLA

Rationale for the Diabetic Retinopathy Clinical Research Network Treatment Protocol for Center-Involved Diabetic Macular Edema

Objective: Describe the underlying principles used to develop a web-based algorithm that incorporated intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) in a Diabetic Retinopathy Clinical Research Network (DRCR.net) randomized clinical trial. Design: Discussion of treatment protocol for DME. Participants: Subjects with vision loss from DME involving the center of the macula. Methods: The DRCR.net created an algorithm incorporating anti-VEGF injections in a comparative effectiveness randomized clinical trial evaluating intravitreal ranibizumab with prompt or deferred (≥24 weeks) focal/grid laser in eyes with vision loss from center-involved DME. Results confirmed that intravitreal ranibizumab with prompt or deferred laser provides superior visual acuity outcomes, compared with prompt laser alone through at least 2 years. Duplication of this algorithm may not be practical for clinical practice. In order to share their opinion on how ophthalmologists might emulate the study protocol, participating DRCR.net investigators developed guidelines based on the algorithm's underlying rationale. Main Outcome Measures: Clinical guidelines based on a DRCR.net protocol. Results: The treatment protocol required real time feedback from a web-based data entry system for intravitreal injections, focal/grid laser, and follow-up intervals. Guidance from this system indicated whether treatment was required or given at investigator discretion and when follow-up should be scheduled. Clinical treatment guidelines, based on the underlying clinical rationale of the DRCR.net protocol, include repeating treatment monthly as long as there is improvement in edema compared with the previous month, or until the retina is no longer thickened. If thickening recurs or worsens after discontinuing treatment, treatment is resumed. Conclusions: Duplication of the approach used in the DRCR.net randomized clinical trial to treat DME involving the center of the macula with intravitreal ranibizumab may not be practical in clinical practice, but likely can be emulated based on an understanding of the underlying rationale for the study protocol. Inherent differences between a web-based treatment algorithm and a clinical approach may lead to differences in outcomes that are impossible to predict. The closer the clinical approach is to the algorithm used in the study, the more likely the outcomes will be similar to those published

Metamodernism, the Anthropocene, and the Resurgence of Historicity: Ben Lerner’s 10:04 and “the utopian glimmer of fiction”

Postmodernism has been characterized by a reductive presentism that suppresses historicity and neglects the possibility of the future. If we have seen a shift from postmodernism to a different cultural logic and structure of feeling—as, indeed, many critics argue—it therefore follows that this may also entail a new dominant in temporal dynamics. In this article, I take Ben Lerner’s 2014 novel 10:04 as a case study in literary metamodernism, though I also make reference to Adam Thirlwell’s 2011 novella Kapow! and Ruth Ozeki’s 2013 novel A Tale for the Time Being. Across these texts, and primarily in 10:04 as a quintessentially metamodernist fiction, I observe and explicate a metamodern temporality characterized, interconnectedly, by the aesthetics of heterochrony, sideshadowing, and the anticipation of retrospection. Whilst this temporal dynamic emerges from the precarity and volatility of experience in the twenty-first century, anthropocenic climate change has been and remains—I suggest—the greatest catalyst in producing this new temporal experience which resurrects historicity and resuscitates the future as a field of possibilities

Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo

Meeting Abstracts: Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo Clearwater Beach, FL, USA. 9-11 June 201

Precise quantification of cellular uptake of cell-penetrating peptides using fluorescence-activated cell sorting and fluorescence correlation spectroscopy

AbstractCell-penetrating peptides (CPPs) have emerged as a potentially powerful tool for drug delivery due to their ability to efficiently transport a whole host of biologically active cargoes into cells. Although concerted efforts have shed some light on the cellular internalization pathways of CPPs, quantification of CPP uptake has proved problematic. Here we describe an experimental approach that combines two powerful biophysical techniques, fluorescence-activated cell sorting (FACS) and fluorescence correlation spectroscopy (FCS), to directly, accurately and precisely measure the cellular uptake of fluorescently-labeled molecules. This rapid and technically simple approach is highly versatile and can readily be applied to characterize all major CPP properties that normally require multiple assays, including amount taken up by cells (in moles/cell), uptake efficiency, internalization pathways, intracellular distribution, intracellular degradation and toxicity threshold. The FACS–FCS approach provides a means for quantifying any intracellular biochemical entity, whether expressed in the cell or introduced exogenously and transported across the plasma membrane

The Conformational Ensembles of a-Synuclein and Tau: Combining Single-Molecule FRET and Simulations

Peer reviewe

Single Molecule Characterization of α-Synuclein in Aggregation-Prone States

α-Synuclein (αS) is an intrinsically disordered protein whose aggregation into ordered, fibrillar structures underlies the pathogenesis of Parkinson's disease. A full understanding of the factors that cause its conversion from soluble protein to insoluble aggregate requires characterization of the conformations of the monomer protein under conditions that favor aggregation. Here we use single molecule Förster resonance energy transfer to probe the structure of several aggregation-prone states of αS. Both low pH and charged molecules have been shown to accelerate the aggregation of αS and induce conformational changes in the protein. We find that at low pH, the C-terminus of αS undergoes substantial collapse, with minimal effect on the N-terminus and central region. The proximity of the N- and C-termini and the global dimensions of the protein are relatively unaffected by the C-terminal collapse. Moreover, although compact at low pH, with restricted chain motion, the structure of the C-terminus appears to be random. Low pH has a dramatically different effect on αS structure than the molecular aggregation inducers spermine and heparin. Binding of these molecules gives rise to only minor conformational changes in αS, suggesting that their mechanism of aggregation enhancement is fundamentally different from that of low pH

Studies in green: teaching ecological crime fiction

Crime and detective fictions are inherently concerned with the ways in which ambiance, cultural geographies and place attachments may be factors in the instigation and detection of crime. Through readings of classic detective stories by Arthur Conan Doyle and recent Niger Delta petrofictions, this chapter explores ways of teaching those crime narratives which have pushed further, forcing detectives and readers to think beyond human dramas and to explore the roles that environmental factors, agencies and crises play in human transgression. Bringing ecocritical perspectives into the teaching of crime fiction may be challenging, but can engage students in some of the most demanding ethical, aesthetic and political questions of our time