There is current scientific interest in naturally sourced phenolic compounds and their potential benefits to health, as well as the effective role polyphenols may provide in an exercise setting. This ...study investigated the chronic effects of supplementation with a biodynamic and organic olive fruit water phytocomplex (OliPhenolia® OliP), rich in hydroxytyrosol (HT), on submaximal and exhaustive exercise performance and respiratory markers of recovery. Twenty-nine recreationally active participants (42 ± 2 yrs; 71.1 ± 2.1 kg; 1.76 ± 0.02 m) consumed 2 × 28 mL∙d−1 of OliP or a taste- and appearance-matched placebo (PL) over 16 consecutive days. Participants completed a demanding, aerobic exercise protocol at ~75% maximal oxygen uptake (V˙O2max) for 65 min 24 h before sub- and maximal performance exercise tests prior to and following the 16-day consumption period. OliP reduced the time constant (τ) (p = 0.005) at the onset of exercise, running economy (p = 0.015) at lactate threshold 1 (LT1), as well as the rating of perceived exertion (p = 0.003) at lactate turnpoint (LT2). Additionally, OliP led to modest improvements in acute recovery based upon a shorter time to achieve 50% of the end of exercise V˙O2 value (p = 0.02). Whilst OliP increased time to exhaustion (+4.1 ± 1.8%), this was not significantly different to PL (p > 0.05). Phenolic compounds present in OliP, including HT and related metabolites, may provide benefits for aerobic exercise and acute recovery in recreationally active individuals. Further research is needed to determine whether dose-response or adjunct use of OliP alongside longer-term training programs can further modulate exercise-associated adaptations in recreationally active individuals, or indeed support athletic performance.
Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype for which no effective targeted therapies are available. Growing evidence suggests that chemotherapy-resistant cancer cells ...with stem-like properties (CSC) may repopulate the tumor. The androgen receptor (AR) is expressed in up to 50% of TNBCs, and AR inhibition decreases CSC and tumor initiation. Runt-related transcription factor 1 (RUNX1) correlates with poor prognosis in TNBC and is regulated by the AR in prostate cancer. Our group has shown that RUNX1 promotes TNBC cell migration and regulates tumor gene expression. We hypothesized that RUNX1 is regulated by the AR and that both may work together in TNBC CSC to promote disease recurrence following chemotherapy. Chromatin immunoprecipitation sequencing (ChIP-seq) experiments in MDA-MB-453 revealed AR binding to
regulatory regions. RUNX1 expression is upregulated by dihydrotestosterone (DHT) in MDA-MB-453 and in an AR
-TNBC HCI-009 patient-derived xenograft (PDX) tumors (
< 0.05). RUNX1 is increased in a CSC-like experimental model in MDA-MB-453 and SUM-159PT cells (
< 0.05). Inhibition of RUNX1 transcriptional activity reduced the expression of CSC markers. Interestingly, RUNX1 inhibition reduced cell viability and enhanced paclitaxel and enzalutamide sensitivity. Targeting RUNX1 may be an attractive strategy to potentiate the anti-tumor effects of AR inhibition, specifically in the slow-growing CSC-like populations that resist chemotherapy which lead to metastatic disease.
Peripapillary retinoschisis is associated with primary and secondary glaucoma. It is important that clinicians are familiar with the presentation and management of peripapillary retinoschisis to ...understand its effects on the patient's glaucoma and to avoid unnecessary referral when the macula is not involved.
We present a case of peripapillary retinoschisis found incidentally on routine optical coherence tomographic (OCT) surveillance of primary open-angle glaucoma.
A 70-year-old man presented for his annual diabetic eye examination. Surveillance with OCT revealed a splitting of the inner peripapillary retina corresponding to a previously noted notch in the right optic nerve. Further imaging of the right eye using enhanced depth imaging OCT revealed a defect in the lamina cribrosa that may have contributed to the formation and persistence of peripapillary retinoschisis. Retinal nerve fiber layer analysis showed a 5-year history of progressive temporal and inferotemporal thickening in the right eye. The patient was managed conservatively with instruction on regular Amsler grid testing.
As seen in this case, peripapillary retinoschisis typically alters retinal nerve fiber layer thickness on OCT and can be mistakenly attributed to glaucomatous change. Glaucoma-associated peripapillary retinoschisis is usually not vision threatening and can be managed conservatively; in rare cases of progression to macular involvement, patients should be referred to a retina specialist.
In the last few decades, numerous studies pertaining to research groups worldwide have investigated the effects of oral caffeine intake on fat oxidation at rest, during exercise, and after exercise. ...However, there is no bibliometric analysis to assess the large volume of scientific output associated with this topic. A bibliometric analysis of this topic may be used by researchers to assess the current scientific interest in the application of caffeine as a nutritional strategy to augment fat oxidation, the journals with more interest in this type of publication, and to draw international collaborations between groups working in the same area. For these reasons, the purpose of this study was to assess the research activity regarding oral caffeine intake and fat oxidation rate in the last few decades by conducting a bibliometric and visual analysis. Relevant publications from 1992 to 2022 were retrieved from the Web of Science (WoS) Core Collection database. Quantitative and qualitative variables were collected, including the number of publications and citations, H-indexes, journals of citation reports, co-authorship, co-citation, and the co-occurrence of keywords. There were 182 total publications, while the number of annual publications is saw-shaped with a modest increase of 11.3% from 2000 to 2009 to 2010 to 2019. The United States was the country with the highest number of publications (24.17% of the total number of articles), followed by the Netherlands (17.03%). According to citation analyses, the average number of citations per document is 130, although there are 21 documents that have received more than 100 citations; the most cited document reached 644 citations. These citation data support the overall relevance of this topic in the fields of nutrition and dietetics and sport sciences that when combined harbored 85.71% of all articles published in the WoS. The most productive author was Westerterp-Plantenga with 16 articles (8.79% of the total number of articles). Nutrients was the journal that published the largest number of articles on this topic (6.59% of the total number of articles). Last, there is a tendency to include keywords such as “performance”, “carbohydrate”, and “ergogenic aid” in the newer articles, while “obesity”, “thermogenic”, and “tea” are the keywords more commonly included in older documents. Although research into the role of caffeine on fat oxidation has existed since the 1970s, our analysis suggests that the scientific output associated with this topic has progressively increased since 1992, demonstrating that this is a nutritional research area with a strong foundational base of scientific evidence. Based on the findings of this bibliometric analysis, future investigation may consider focusing on the effects of sex and tolerance to caffeine to widen the assessment of the effectiveness of oral caffeine intake as a nutritional strategy to augment the use of fat as a fuel, as these terms rarely appear in the studies included in this analysis. Additionally, more translational research is necessary as the studies that investigate the effect of oral caffeine intake in ecologically valid contexts (i.e., exercise training programs for individuals with excessive adiposity) are only a minor part of the studies on this topic.
OBJECTIVES/GOALS: The CDC estimates that Influenza infections account for an average of 420,000 hospitalizations and 34,700 deaths in the U.S. each year. This project explores the underlying ...mechanisms of the infectious process of Influenza A in human lung organoids by examining the differential transcriptomic expression compared to uninfected controls. METHODS/STUDY POPULATION: Lung organoids were cultured from differentiated human bronchial epithelial cells from lung transplant donors on an air-liquid interface until they were confirmed to contain both mucous producing and ciliated cells. Lung organoids are ideal models in translational science due to their structural and functional characteristics which closely mimic those of in vivo human epithelial tissue. Half the organoids were exposed to Influenza A pH1N1 for 72h; the other half served as uninfected controls. RNA was isolated from both groups and sequenced using the Oxford Nanopore MinION which generates full length reads. Reads were aligned to the human reference genome (GRCh38.p14) using Minimap2. RESULTS/ANTICIPATED RESULTS: The MinION sequenced an average of 3.24m reads per sample and a total of 13,128 genes were relevantly expressed (defined as greater than 1 read per million in at least half the samples). ANOVA with a 5% false discovery rate (Benjamini and Hochberg correction) revealed 5,417 differentially expressed genes between infected and control groups. Within this subset, we identified downregulation of mucociliary clearance, mitochondrial and ß-oxidation, peroxisome, and glutathione replenishment genes. We further identified upregulation in inflammatory markers, lactate dehydrogenase enzymes, and several s100 proteins. The downregulation of mitochondrial and β-oxidation markers and the upregulation of lactate dehydrogenase enzymes revealed a Warburg-like phenotype which has not previously been reported. DISCUSSION/SIGNIFICANCE: This study reveals a novel Warburg-like phenotype in Influenza A infection alongside downregulated mucociliary clearance and upregulated inflammatory processes. These findings improve our understanding of Influenza A infection and point to potential therapeutic targets to advance precision medicine approaches to treatment.
By using deceptive experiments in which participants are informed that they received caffeine when, in fact, they received an inert substance (i.e., placebo), several investigations have demonstrated ...that exercise performance can be enhanced to a similar degree as a known caffeine dose. This 'placebo effect' phenomenon may be part of the mechanisms explaining caffeine's ergogenicity in exercise. However, there is no study that has established whether the placebo effect of caffeine is also present for other benefits obtained with acute caffeine intake, such as enhanced fat oxidation during exercise. Therefore, the aim of this investigation was to investigate the placebo effect of caffeine on fat oxidation during exercise. Twelve young men participated in a deceptive double-blind cross-over experiment. Each participant completed three identical trials consisting of a step incremental exercise test from 30 to 80% of V.O
. In the two first trials, participants ingested either 3 mg/kg of cellulose (placebo) or 3 mg/kg of caffeine (received caffeine) in a randomized order. In the third trial, participants were informed that they had received 3 mg/kg of caffeine, but a placebo was provided (informed caffeine). Fat oxidation rates were derived from stoichiometric equations. In received caffeine, participants increased their rate of fat oxidation over the values obtained with the placebo at 30%, 40%, 50%, and 60% of V.O
(all
< 0.050). In informed caffeine, participants increased their rate of fat oxidation at 30%, 40%, 50% 60%, and 70% of V.O
(all
< 0.050) over the placebo, while there were no differences between received versus informed caffeine. In comparison to placebo (0.32 ± 0.15 g/min), the rate of maximal fat oxidation was higher in received caffeine (0.44 ± 0.22 g/min,
= 0.045) and in informed caffeine (0.41 ± 0.20 g/min,
= 0.026) with no differences between received versus informed caffeine. However, the intensity at which maximal fat oxidation rate was obtained (i.e., Fat
) was similar in placebo, received caffeine, and informed caffeine trials (42.5 ± 4.5, 44.2 ± 9.0, and 41.7 ± 10.5% of V.O
, respectively,
= 0.539). In conclusion, the expectancy of having received caffeine produced similar effects on fat oxidation rate during exercise than actually receiving caffeine. Therefore, the placebo effect of caffeine is also present for the benefits of acute caffeine intake on substrate oxidation during exercise and it may be used to enhance fat oxidation during exercise in participants while reducing any risks to health that this substance may have.
Objectives
The objective of this study was to assess the impact of an emergency department (ED) deprescribing intervention for geriatric adults. We hypothesized that pharmacist‐led medication ...reconciliation for at‐risk aging patients would increase the 60‐day case rate of primary care provider (PCP) deprescribing of potentially inappropriate medications (PIMs).
Methods
This was a retrospective, before‐and‐after intervention pilot study conducted at an urban Veterans Affairs ED. In November 2020, a protocol utilizing pharmacists to perform medication reconciliations for patients 75 years or older who screened positive using an Identification of Seniors at Risk tool at triage was implemented. Reconciliations focused on identifying PIMs and providing deprescribing recommendations to patients' PCPs. A preintervention group was collected between October 2019 and October 2020, and a postintervention group was collected between February 2021 to February 2022. The primary outcome compared case rates of PIM deprescribing in the preintervention group to the postintervention group. Secondary outcomes include per‐medication PIM deprescribing rate, 30‐day PCP follow‐up visits, 7‐ and 30‐day ED visits, 7‐ and 30‐day hospitalizations, and 60‐day mortality.
Results
A total of 149 patients were analyzed in each group. Both groups were similar in age and sex, with an average age of 82 years and 98% male. The case rate of PIM deprescribing at 60 days was 11.1% preintervention compared to 57.1% postintervention (p < 0.001). Preintervention, 91% of PIMs remained unchanged at 60 days compared to 49% (p < 0.05) postintervention. Regardless of PIM identification, the 30‐day primary care follow‐up rate increased postintervention: 31.5% and 55.7% (p < 0.0001), respectively. There was no improvement in 7‐ or 30‐day subsequent ED visits, hospitalization, or mortality.
Conclusions
Pharmacist‐led medication reconciliation in high‐risk geriatric patients was associated with an increase both in the rate of PIM deprescribing and in post‐ED primary care engagement.
Dietary manipulation with high-protein or high-carbohydrate content are frequently employed during elite athletic training, aiming to enhance athletic performance. Such interventions are likely to ...impact upon gut microbial content. This study explored the impact of acute high-protein or high-carbohydrate diets on measured endurance performance and associated gut microbial community changes. In a cohort of well-matched, highly trained endurance runners, we measured performance outcomes, as well as gut bacterial, viral (FVP), and bacteriophage (IV) communities in a double-blind, repeated-measures design randomized control trial (RCT) to explore the impact of dietary intervention with either high-protein or high-carbohydrate content. High-dietary carbohydrate improved time-trial performance by +6.5% (
< 0.03) and was associated with expansion of
and
bacterial spp. Conversely, high dietary protein led to a reduction in performance by -23.3% (
= 0.001). This impact was accompanied by significantly reduced diversity (IV:
= 0.04) and altered composition (IV and FVP:
= 0.02) of the gut phageome as well as enrichment of both free and inducible
and
bacterial populations. Greatest performance during dietary modification was observed in participants with less substantial shifts in community composition. Gut microbial stability during acute dietary periodization was associated with greater athletic performance in this highly trained, well-matched cohort. Athletes, and those supporting them, should be mindful of the potential consequences of dietary manipulation on gut flora and implications for performance, and periodize appropriately.
Dietary periodization is employed to improve endurance exercise performance but may impact on gut microbial communities. Bacteriophage are implicated in bacterial cell homeostasis and have been identified as biomarkers of disequilibrium in the gut ecosystem possibly brought about through dietary periodization. We find high-carbohydrate and high-protein diets to have opposing impacts on endurance performance in highly trained athlete populations. Reduced performance is linked with disturbance of microbial stasis in the gut. We demonstrate bacteriophage communities are the most sensitive component of the gut microbiota to increased gut stress following dietary manipulation. Athletes undertaking dietary periodization should be aware of potential negative impacts of drastic changes to dietary composition on gut microbial stasis and, in turn, endurance performance.
British Army Phase One training exposes men and women to challenging distances of 13.5 km·d
vs. 11.8 km·d
and energy expenditures of ~ 4000 kcal·d
and ~ 3000 kcal·d
, respectively. As such, it is ...essential that adequate nutrition is provided to support training demands. However, to date, there is a paucity of data on habitual dietary intake of British Army recruits. The aims of this study were to: (i) compare habitual dietary intake in British Army recruits undergoing Phase One training to Military Dietary Reference Values (MDRVs), and (ii) establish if there was a relative sex difference in dietary intake between men and women.
Researcher led weighed food records and food diaries were used to assess dietary intake in twenty-eight women (age 21.4 ± 3.0 yrs., height: 163.7 ± 5.0 cm, body mass 65.0 ± 6.7 kg), and seventeen men (age 20.4 ± 2.3 yrs., height: 178.0 ± 7.9 cm, body mass 74.6 ± 8.1 kg) at the Army Training Centre, Pirbright for 8-days in week ten of training. Macro and micronutrient content were estimated using dietary analysis software (Nutritics, Dublin) and assessed via an independent sample t-test to establish if there was a sex difference in daily energy, macro or micronutrient intakes.
Estimated daily energy intake was less than the MDRV for both men and women, with men consuming a greater amount of energy compared with women (2846 ± 573 vs. 2207 ± 585 kcal·day
, p < 0.001). Both sexes under consumed carbohydrate (CHO) when data was expressed relative to body mass with men consuming a greater amount than women (4.8 ± 1.3 vs. 3.8 ± 1.4 g·kg
·day
, p = 0.025, ES = 0.74). Both sexes also failed to meet MDRVs for protein intake with men consuming more than women (1.5 ± 0.3 vs. 1.3 ± 0.3 g·kg
·day
, p > 0.030, ES = 0.67). There were no differences in dietary fat intake between men and women (1.5 ± 0.2 vs. 1.5 ± 0.5 g·kg
·day
, p = 0.483, ES = 0.00).
Daily EI in men and women in Phase One training does not meet MDRVs. Interventions to increase macronutrient intakes should be considered along with research investigating the potential benefits for increasing different macronutrient intakes on training adaptations.
PDF
