Fuel for the Work Required: A Theoretical Framework for Carbohydrate Periodization and the Glycogen Threshold Hypothesis.

Deliberately training with reduced carbohydrate (CHO) availability to enhance endurance-training-induced metabolic adaptations of skeletal muscle (i.e. the 'train low, compete high' paradigm) is a hot topic within sport nutrition. Train-low studies involve periodically training (e.g., 30-50% of training sessions) with reduced CHO availability, where train-low models include twice per day training, fasted training, post-exercise CHO restriction and 'sleep low, train low'. When compared with high CHO availability, data suggest that augmented cell signalling (73% of 11 studies), gene expression (75% of 12 studies) and training-induced increases in oxidative enzyme activity/protein content (78% of 9 studies) associated with 'train low' are especially apparent when training sessions are commenced within a specific range of muscle glycogen concentrations. Nonetheless, such muscle adaptations do not always translate to improved exercise performance (e.g. 37 and 63% of 11 studies show improvements or no change, respectively). Herein, we present our rationale for the glycogen threshold hypothesis, a window of muscle glycogen concentrations that simultaneously permits completion of required training workloads and activation of the molecular machinery regulating training adaptations. We also present the 'fuel for the work required' paradigm (representative of an amalgamation of train-low models) whereby CHO availability is adjusted in accordance with the demands of the upcoming training session(s). In order to strategically implement train-low sessions, our challenge now is to quantify the glycogen cost of habitual training sessions (so as to inform the attainment of any potential threshold) and ensure absolute training intensity is not compromised, while also creating a metabolic milieu conducive to facilitating the endurance phenotype

Restricted Attentional Capacity within but Not between Sensory Modalities: An Individual Differences Approach

Background Most people show a remarkable deficit to report the second of two targets when presented in close temporal succession, reflecting an attentional blink (AB). An aspect of the AB that is often ignored is that there are large individual differences in the magnitude of the effect. Here we exploit these individual differences to address a long-standing question: does attention to a visual target come at a cost for attention to an auditory target (and vice versa)? More specifically, the goal of the current study was to investigate a) whether individuals with a large within-modality AB also show a large cross-modal AB, and b) whether individual differences in AB magnitude within different modalities correlate or are completely separate. Methodology/Principal Findings While minimizing differential task difficulty and chances for a task-switch to occur, a significant AB was observed when targets were both presented within the auditory or visual modality, and a positive correlation was found between individual within-modality AB magnitudes. However, neither a cross-modal AB nor a correlation between cross-modal and within-modality AB magnitudes was found. Conclusion/Significance The results provide strong evidence that a major source of attentional restriction must lie in modality-specific sensory systems rather than a central amodal system, effectively settling a long-standing debate. Individuals with a large within-modality AB may be especially committed or focused in their processing of the first target, and to some extent that tendency to focus could cross modalities, reflected in the within-modality correlation. However, what they are focusing (resource allocation, blocking of processing) is strictly within-modality as it only affects the second target on within-modality trials. The findings show that individual differences in AB magnitude can provide important information about the modular structure of human cognition

Gut microbiota-derived propionate reduces cancer cell proliferation in the liver

Peer reviewedPublisher PD

Telomeric expression sites are highly conserved in trypanosoma brucei

Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology

Management information systems for community based interventions to improve health::Qualitative study of stakeholder perspectives

Abstract Background Community based providers are well place to deliver behavioural interventions to improve health. Good project management and reliable outcome data are needed to efficiently deliver and evaluate such interventions, and Management information systems (MIS) can facilitate these processes. We explored stakeholders perspectives on the use of MIS in community based behavioural interventions. Methods Stakeholders, purposively selected to provide a range of MIS experience in the delivery of community based behavioural interventions to improve health (public health commissioners, intervention service managers, project officers, health researchers and MIS designers), were invited to participate in individual semi-structured interviews. We used a topic guide and encouraged stakeholders to reflect on their experiences.: Interviews were recorded, transcribed and analysed using five steps of Framework analysis. We applied an agreed coding framework and completed the interviews when no new themes emerged. Results We interviewed 15 stakeholders. Key themes identified were: (i) MIS access; (ii) data and its function; (iii) MIS development and updating. Within these themes the different experiences, needs, use, training and expertise of stakeholders and the variation and potential of MIS were evidenced. Interviews advised the need to involve stakeholders in MIS design and development, build-in flexibility to accommodate MIS refinement and build on effective MIS. Conclusions Findings advised involving stakeholders, early in the design process. Designs should build on existing MIS of proven utility and ensure flexibility in the design, to incorporate adaptations and ongoing system development in response to early MIS use and evolving stakeholder needs

Intraventricular glioneuronal tumor with disseminated lesions at diagnosis - a case report -

A 55-year-old man presented with a large tumor in his lateral ventricles. Magnetic resonance imaging revealed disseminated lesions in the third and fourth ventricles at the time of diagnosis. The patient underwent a partial removal of the tumor in the lateral ventricles. Histologically, the surgical specimens showed glioneuronal differentiation with ganglion or ganglioid cells, Rosenthal fibers, oligodendroglia-like honeycomb appearances, a spongy pattern, perivascular pseudorosettes, and many hyalinized blood vessels. Papillary structure was not observed. The neuronal component showed a moderately high labeling index of Ki-67/MIB-1. We diagnosed this tumor as atypical intraventricular glioneuronal tumor. The disseminated lesions disappeared after chemoradiation therapy with temozolomide, and the residual tumors in the lateral ventricles remained stable for 3 years after the surgery. We discuss the pathological diagnosis, therapy and clinical course with review of the literatures

Focal non granulomatous orchitis in a patient with Crohn’s disease

Crohn’s disease is a systemic disease and sometimes involves the testicle, usually leading to granulomatous lesions. We report herein a case of focal non-granulomatous orchitis in a 21-year-old patient with active Crohn’s disease treated by an anti-tumor necrosis factor monoclonal antibody. This circumscribed testicular lesion mimicked a tumor, leading to orchiectomy. Pre-operative blood tests (i.e. alpha-fetoprotein, lactate dehydrogenase and human chorionic gonadotrophin) were strictly normal Pathological examination of the testicle revealed a focal inflammatory infiltrate predominantly composed of lymphocytes accompanied by few plasma cells, lacking giant cells or granulomas. Importantly, intratubular germ cell neoplasia, atrophy or lithiasis were not observed. After discussing and excluding other plausible causes (burnt-out /regressed germ cell tumor, infection, vascular or traumatic lesions, iatrogenic effects), we concluded that this particular case of orchitis was most likely an extra-digestive manifestation of inflammatory bowel disease. To our knowledge, this is the first described case of focal non-granulomatous orchitis associated with Crohn’s disease. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/211774728416011

Graded reductions in pre-exercise muscle glycogen impair exercise capacity but do not augment cell skeletal muscle signalling: implication for CHO periodisation

We examined the effects of graded muscle glycogen on exercise capacity and modulation of skeletal muscle signalling pathways associated with the regulation of mitochondrial biogenesis. In a repeated measures design, eight males completed a sleep-low, train-low model comprising an evening glycogen depleting cycling protocol followed by an exhaustive exercise capacity test (8 x 3 min at 80% PPO, followed by 1 min efforts at 80% PPO until exhaustion) the subsequent morning. Following glycogen depleting exercise, subjects ingested a total of 0 g kg-1 (L-CHO), 3.6 g kg-1 (M-CHO) or 7.6 g kg-1 (H-CHO) of carbohydrate during a 6 h period prior to sleeping, such that exercise was commenced the next morning with graded (P < 0.05) muscle glycogen concentrations (Mean ± SD) (L-CHO: 88 ± 43, M-CHO: 185 ± 62, H-CHO: 278 ± 47 mmol kg-1 dw). Despite differences (P < 0.05) in exercise capacity at 80% PPO between trials (L-CHO: 18 ± 7, M-CHO: 36 ± 3, H-CHO: 44 ± 9 min) exercise induced comparable AMPKThr172 phosphorylation (~4 fold) and PGC-1α mRNA expression (~5 fold) post- and 3 h post-exercise, respectively. In contrast, exercise nor CHO availability affected the phosphorylation of p38MAPKThr180/Tyr182, CaMKIIThr268 or mRNA expression of p53, Tfam, CPT-1, CD36 or PDK4. Data demonstrate that when exercise is commenced with muscle glycogen below 300 mmol kg-1 dw, further graded reductions of 100 mmol kg-1 dw impair exercise capacity but do not augment skeletal muscle cell signaling