Repeated Sprints in Fasted State Impair Reaction Time Performance

Objective: The aim of this study was to assess the effects of 3-day Islamic intermittent fasting (3d-IF) on cognitive performance and serum levels of neurotrophic factors (brain-derived neurotrophic factor [BDNF] and vascular endothelial growth factor [VEGF]) before and after repeated sprints.

Methods: Twenty-one physically active male Muslims (29.8 ± 5.9 years, exercising 4 ± 1.5 times/week) were randomly assigned to one of 2 experimental sessions: the control or nonfasting session (CS) or the fasting session (FS). These 2 sessions occurred 7 days apart in a counterbalanced crossover design. In both conditions, the test was performed at the same time of day, approximately 1 hour before sunset. In the FS, the test occurred on the third day of the 3d-IF and involved the participants' performance of the following: (a) two series of 5 maximal 5-second sprints and (b) 2 cognitive tasks: One Touch Stockings (OTS) and reaction time (simple and complex RTI).

Results: In both conditions, the participants' reaction times during the RTI test were similar at the pre- and mid-exercise points, but postexercise, simple and complex reaction times were higher in FS compared to CS (p = 0.045, effect size [ES] = 0.21 and p = 0.006, ES = 0.41, respectively). However, OTS performance and serum levels of neurotrophic factors were not influenced by the 3d-IF.

Conclusion: Simple and complex reaction times during the RTI test were negatively affected by the 3d-IF after 2 bouts of intensive repeated sprints.     

Prostate Cancer Ambassadors: Enhancing a Theory-Informed Training Program for Informed Decision-Making

Despite the high burden of prostate cancer in African American communities, there is a paucity of knowledge about prostate health. This paper describes the enhancement of a curriculum for training lay health advisors, called prostate cancer ambassadors, on informed decision-making for prostate cancer screening. Adult learning theory informed the structuring of the training sessions to be interactive, self-directed, and engaging. Trainings were developed in a manner that made the material relevant to the learners and encouraged co-learning. The research team developed strategies, such as using discussions and interactive activities, to help community members weigh the pros and cons of prostate-specific antigen (PSA) screening and to make an informed decision about screening. Furthermore, activities were developed to bolster four social cognitive theory constructs: observational learning, self-efficacy for presenting information to the community and for making an informed decision themselves, collective efficacy for presenting information to the community, and outcome expectations from those presentations. Games, discussions, and debates were included to make learning fun and encourage discovery. Practice sessions and team-building activities were designed to build self-efficacy for sharing information about informed decision-making. Topics added to the original curriculum included updates on prostate cancer screening, informed decision-making for screening, skills for being a lay health advisor, and ethics. This dynamic model and approach to lay health advisor (ambassador) training is flexible: while it was tailored for use with prostate cancer education, it can be adjusted for use with other types of cancer and even other diseases.     

A novel mixed living high training low intervention and the hematological module of the athlete biological passport

Exposure to either natural or simulated hypoxia induces hematological adaptations that may affect the parameters of the Athlete Biological Passport (ABP). The aim of the present study was to examine the effect of a novel, mixed hypoxic dose protocol on the likelihood of producing an atypical ABP finding. Ten well‐trained middle‐distance runners participated in a “live high, train low and high” (LHTLH) altitude training camp for 14 days. The participants spent ?6 hr.d‐1 at 3000–5400 m during waking hours and ?10 h.d‐1 overnight at 2400–3000 m simulated altitude. Venous blood samples were collected before (B0), and after 1 (D1), 4 (D4), 7 (D7), and 14 (D14) days of hypoxic exposure, and again 14 days post exposure (P14). Samples were analyzed for key parameters of the ABP including reticulocyte percentage (Ret%), hemoglobin concentration ([Hb]), and the OFF‐score. The ABP adaptive model was administered at a specificity of 99% to test for atypical findings. We found significant changes in [Hb] and Ret% during the hypoxic intervention. Consequently, this led to ABP threshold deviations at 99% specificity in three participants. Only one of these was flagged as an “atypical passport finding” (ATPF) due to deviation of the OFF‐score. When this sample was evaluated by ABP experts it was considered “normal”. In conclusion, it is highly unlikely that the present hypoxic exposure protocol would have led to a citation for a doping violation according to WADA guidelines.     

Characterization of in vivo pharmacokinetic properties of the dopamine D1 receptor agonist DAR-0100A in nonhuman primates using PET with [11C] NNC112 and [11C] raclopride

DAR-0100A, the active enantiomer of dihydrexidine, is a potent dopamine D1 agonist under investigation for treatment of cognitive impairment and negative symptoms of schizophrenia. We measured the dose–occupancy relationship for DAR-0100A at D1 receptors using positron emission tomography (PET) imaging in baboons with [¹¹C] NNC112 and its binding to D2 with [¹¹C] raclopride. Two baboons were scanned with [¹¹C] NNC112 at baseline and after three different doses of DAR-0100A. Two baboons were scanned with [¹¹C] raclopride at baseline and after one dose of DAR-0100A. Occupancy (ΔBP_ND) was computed in the striatum and cortex. A clear relationship was observed between plasma concentration of DAR-0100A and ΔBP_ND. ΔBP_ND was larger in the striatum than in the cortex, consistent with reports showing that 25% of [¹¹C] NNC112 BP_ND in the cortex is attributed to 5-HT_2A. Plasma EC₅₀ estimates ranged from 150 to 550 ng/mL according to the constraints on the model. There was no detectable effect of DAR-0100A on [¹¹C] raclopride BP_ND. These data suggest that at doses likely to be administered to patients, occupancy will not be detectable with [¹¹C] NNC112 PET and binding of DAR-0100A to D2 will be negligible. This is the first demonstration with PET of a significant occupancy by a full D1 agonist in vivo.     

Effects of the D1 Dopamine Receptor Agonist Dihydrexidine (DAR-0100A) on Working Memory in Schizotypal Personality Disorder

Pharmacological enhancement of prefrontal D₁ dopamine receptor function remains a promising therapeutic approach to ameliorate schizophrenia-spectrum working memory deficits, but has yet to be rigorously evaluated clinically. This proof-of-principle study sought to determine whether the active enantiomer of the selective and full D₁ receptor agonist dihydrexidine (DAR-0100A) could attenuate working memory impairments in unmedicated patients with schizotypal personality disorder (SPD). We performed a randomized, double-blind, placebo-controlled trial of DAR-0100A (15 mg/150 ml of normal saline administered intravenously over 30 min) in medication-free patients with SPD (n=16) who met the criteria for cognitive impairment (ie, scoring below the 25th percentile on tests of working memory). We employed two measures of verbal working memory that are salient to schizophrenia-spectrum cognitive deficits, and that clinical data implicate as being associated with prefrontal D₁ availability: (1) the Paced Auditory Serial Addition Test (PASAT); and (2) the N-back test (ratio of 2-back:0-back scores). Study procedures occurred over four consecutive days, with working memory testing on Days 1 and 4, and DAR-0100A/placebo administration on Days 2–4. Treatment with DAR-0100A was associated with significantly improved PASAT performance relative to placebo, with a very large effect size (Cohen''s d=1.14). Performance on the N-back ratio was also significantly improved; however, this effect rested on both a non-significant enhancement and diminution of 2-back and 0-back performance, respectively; therefore interpretation of this finding is more complicated. DAR-0100A was generally well tolerated, with no serious medical or psychiatric adverse events; common side effects were mild to moderate and transient, consisting mainly of sedation, lightheadedness, tachycardia, and hypotension; however, we were able to minimize these effects, without altering the dose, with supportive measures, eg, co-administered normal saline. Although preliminary, these findings lend further clinical support to the potential of D₁ receptor agonists to treat schizophrenia-spectrum working memory impairments. These data suggest a need for further studies with larger group sizes, serum DAR-0100A levels, and a more comprehensive neuropsychological battery.     

Prevention of atrial fibrillation onset by beta-blocker treatment in heart failure: a meta-analysis.

AIMS: Atrial fibrillation (AF) is an important morbidity-mortality risk factor, especially in patients with heart failure (HF). Beta-blockers reduce morbidity and mortality in HF. The study was designed to estimate the preventive efficacy of beta-blocker treatment on AF occurrence in patients with HF. METHODS AND RESULTS: A systematic review of the literature was performed to identify all clinical trials evaluating beta-blockers' efficacy in HF. Eligible studies had to be randomized, placebo-controlled and providing information on the incidence of AF during follow-up among those with sinus rhythm at baseline. A total of seven studies which included 11 952 patients receiving a background treatment with angiotensin-converting enzyme-inhibitors could be found. Overall, beta-blockers significantly reduced incidence of onset of AF from 39 to 28 per 1000 patient-years: relative risk reduction=27% (95% confidence interval 14-38, P<0.001); heterogeneity test: P=0.096. A same trend of efficacy was observed in all trials except the SENIORS study. In this trial which included aged patients (>70 years) with systolic or diastolic HF, a higher prevalence of AF at baseline (35%) was observed compared with the mean baseline prevalence (13%). CONCLUSION: Beta-blockers appear to effectively prevent occurrence of AF in patients with systolic HF.     

A novel mutation in the DLG3 gene encoding the synapse-associated protein 102 (SAP102) causes non-syndromic mental retardation

We have identified a novel splice site mutation (IVS6-1G?>?A) in the disc-large homolog 3 (DLG3) gene, encoding the synapse-associated protein 102 (SAP102) in one out of 300 families with moderate to severe non-syndromic mental retardation. SAP102 is a member of the neuronal membrane-associated guanylate kinase protein subfamily comprising SAP97, postsynaptic density (PSD)95, and PSD93, which interacts with methyl-d-aspartate receptor and associated protein complexes at the postsynaptic density of excitatory synapses. DLG3 is the first mental retardation gene directly linked to glutamate receptor signalling and trafficking, increasingly recognised as a central mechanism in the regulation of synaptic formation and plasticity in brain and cognitive development.     

Fibrolipoma of the median nerve

Neural fibrolipoma or fibrolipomatous hamartoma is an uncommon benign tumor that usually arises in the median nerve. Fibrofatty tissue proliferates around the nerve and infiltrates the epineurium and perineurium. We report a case of fibrolipomatous hamartoma of the left median nerve in an 18-year-old woman. Our objective was to describe the pathognomonic magnetic resonance imaging features, whose presence obviates the need for a diagnostic biopsy.