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IntroductionA growing body of evidence suggests that specific, naturally occurring gut bacteria are under-represented in the intestinal tracts of subjects with type 2 diabetes (T2D) and that their functions, like gut barrier stability and butyrate production, are important to glucose and insulin homeostasis. The objective of this study was to test the hypothesis that enteral exposure to microbes with these proposed functions can safely improve clinical measures of glycemic control and thereby play a role in the overall dietary management of diabetes.Research design and methodsWe evaluated whether a probiotic comprised of these anaerobic bacteria would enhance dietary management by (1) manufacturing two novel probiotic formulations containing three (WBF-010) or five (WBF-011) distinct strains in a Current Good Manufacturing Practice (cGMP) facility, (2) establishing consistent live-cell concentrations, (3) confirming safety at target concentrations dispensed in both animal and human studies and (4) conducting a 12-week parallel, double-blind, placebo-controlled, proof-of-concept study in which subjects previously diagnosed with T2D (n=76) were randomly assigned to a two times a day regimen of placebo, WBF-010 or WBF-011.ResultsNo safety or tolerability issues were observed. Compared with the placebo group, subjects administered WBF-011 (which contains inulin, Akkermansia muciniphila, Clostridium beijerinckii, Clostridium butyricum, Bifidobacterium infantis and Anaerobutyricum hallii) significantly improved in the primary outcome, glucose total area under the curve (AUC): −36.1 mg/dL/180 min, p=0.0500 and also improved in secondary outcomes, glycated hemoglobin (A1c): −0.6, glucose incremental-AUC: −28.6 mg/dL/180 min.ConclusionsTo our knowledge, this is the first randomized controlled trial to administer four of the five strains to human subjects with T2D. This proof-of-concept study (clinical trial number NCT03893422) shows that the intervention was safe and well tolerated and that supplementation with WBF-011 improves postprandial glucose control. The limited sample size and intersubject variability justifies future studies designed to confirm and expand on these observations.

Background An increasing body of evidence implicates the resident gut microbiota as playing a critical role in type 2 diabetes (T2D) pathogenesis. We previously reported significant improvement in postprandial glucose control in human participants with T2D following 12-week administration of a 5-strain novel probiotic formulation (‘WBF-011’) in a double-blind, randomized, placebo controlled setting (NCT03893422). While the clinical endpoints were encouraging, additional exploratory measurements were needed in order to link the motivating mechanistic hypothesis - increased short-chain fatty acids - with markers of disease. Results Here we report targeted and untargeted metabolomic measurements on fasting plasma ( n  = 104) collected at baseline and end of intervention. Butyrate and ursodeoxycholate increased among participants randomized to WBF-011, along with compelling trends between butyrate and glycated haemoglobin (HbA1c). In vitro monoculture experiments demonstrated that the formulation’s C. butyricum strain efficiently synthesizes ursodeoxycholate from the primary bile acid chenodeoxycholate during butyrogenic growth. Untargeted metabolomics also revealed coordinated decreases in intermediates of fatty acid oxidation and bilirubin, potential secondary signatures for metabolic improvement. Finally, improvement in HbA1c was limited almost entirely to participants not using sulfonylurea drugs. We show that these drugs can inhibit growth of formulation strains in vitro. Conclusion To our knowledge, this is the first description of an increase in circulating butyrate or ursodeoxycholate following a probiotic intervention in humans with T2D, adding support for the possibility of a targeted microbiome-based approach to assist in the management of T2D. The efficient synthesis of UDCA by C. butyricum is also likely of interest to investigators of its use as a probiotic in other disease settings. The potential for inhibitory interaction between sulfonylurea drugs and gut microbiota should be considered carefully in the design of future studies.

This tutorial should be utilized for emergency medicine (EM) interns and junior residents. Ophthalmology is characteristically a weak area in both medical school and resident education. Medical students are rarely given formal didactic education on the use of the slit lamp or a systematic approach to examining the eye. For EM residents, this leads to inefficient and uncomfortable encounters with patients with eye complaints. We sought to develop a comprehensive emergency ophthalmology tutorial utilizing asynchronous learning followed by a hands-on skill session that would address this need. By the end of this small group didactic, learners will be able to: 1) demonstrate ability to focus on the various components of the slit lamp exam 2) demonstrate understanding of a systematic approach to the eye exam 3) demonstrate appropriate use of the Diaton, iCare, and Tonopen tonometers. This two-hour small group didactic combines hands-on learning sessions to learn the slit lamp exam and tonometry measurement, with a systematic review of the eye exam to help learners better organize their exams and understand the use of necessary tools. The emergency ophthalmology tutorial was initially designed as an education project in which we collected pre- and post-participation surveys regarding resident comfort with various components of the emergency eye exam. After the course residents received a post-course survey to complete. Given the positive feedback we received from our residents regarding the tutorial, we applied for Institutional Review Board (IRB) approval to publish our retrospective survey data. Our IRB waived the need for participant consent. Twelve emergency medicine residents including 11 interns and one post-graduate year (PGY) 2 resident participated in the emergency ophthalmology tutorial as part of our intern boot camp in July of 2021. Twelve PGY-1 residents initially signed up for the course and filled out the pre-participation survey but one of them was not able to attend their scheduled class, so a PGY-2 resident requested to attend.Prior to the course, we used a Likert scale from 1-7, finding that 61.5% (8/13) of participants felt very uncomfortable with performing slit lamp exams, 84.6% (11/13) felt very uncomfortable with using the Diaton tonometer, 76.9% (10/13) felt very uncomfortable with using the iCare tonometer, and 69.3% (9/13) felt uncomfortable or very uncomfortable with using a systematic approach to examining the eye. After the course, 75% (9/12) of participants felt that the course exceeded expectations in ensuring their ability to perform the subcomponents of the slit lamp exam, 75% (9/12) and 83.3% (10/12) of participants felt that the course exceeded expectations in ensuring their ability to use the Diaton and iCare tonometers, respectively, and 91.7% (11/12) felt that the course exceeded expectations in ensuring their ability to perform a systematic eye exam. Participation in a 2-hour emergency ophthalmology tutorial with assigned asynchronous pre-course work improved emergency medicine resident comfort with various components of the eye exam. Emergency ophthalmology, eye exam, slit lamp, tonometry.

PurposeTo test the effectiveness on recreational female middle-aged runners of a programme of high-intensity interval training (HIIT) for a half-marathon race contrasted to a conventional moderate-intensity continuous training (MICT).MethodsTwenty recreational female runners (40 ± 7 years) followed MICT or HIIT schedules for training a half-marathon. The MICT group trained a mean of 32 km/week at intensities below 80% VO2max. The HIIT group ran 25 km/week at intensities between 80 and 100% VO2max, combined with uphill running and resistance training. Women following HIIT ran 21% less distance and invested 17% less time than those from MICT group. All the women were evaluated at the beginning and end of the training and participated in the same half-marathon run.ResultsWomen following both schedules reduced their previous finishing times by 2–3%, which for HIIT group would have meant rising up to 90 positions out of 1454 participants in the local half-marathon race. The high intensity performed during series of high power output (200 m and 400 m) and resistance sessions in HIIT programme promoted changes that allowed modifying efficiency at high workloads. At the same time, the HIIT training programme elicited changes in oxygen uptake and transport as indicated the cardiorespiratory parameters obtained during recovery in lab tests. Moreover, HIIT registered a 14% baseline decrease in heart rate contrasting to the not significant 6% decrease in MICT.ConclusionsRunners following HIIT training obtained similar registers as with a traditional MICT schedule, expending less time and running shorter distances, yet improving their anaerobic and aerobic power.

(1) Background: half-marathon races are popular among recreational runners, with increases in participation among middle-aged and women. We aimed to determine the effects of two half-marathon training programs on hematological and biochemical markers in middle-aged female recreational runners; (2) Methods: ten women (40 ± 7 years) followed moderate intensity continuous training (MICT), based on running volume below 80% V˙O2max, and another ten women followed high intensity interval training (HIIT) at 80%–100% V˙O2max, with less volume, and combined with eccentric loading exercise. Hematology, plasma osmolality, and plasma markers of metabolic status, muscle damage, inflammatory, and oxidative stress were measured before (S1) and after (S2) training and 24 h after the half-marathon (S3); (3) Results: both training programs had similar moderate effects at S2. However, the acute response at S3 induced different alterations. There was a greater decrease in cholesterol and triglyceride levels in MICT and reductions in markers of damage and inflammation in HIIT. Greater variability in some plasma markers at S3 in MICT suggests that there is inter-individual variability in the response to training; (4) Conclusions: HIIT led to better adaptation to the competition maybe because of the repeated exposure to higher oxygen consumption and eccentric loading exercise.

ObjectiveTo assess the predictive value of four cardiovascular (CV) risk algorithms for identifying high-risk psoriatic arthritis (PsA) patients.MethodsEvaluation of patients with PsA enrolled in the Spanish prospective project CARdiovascular in RheuMAtology. Baseline data of 669 PsA patients with no history of CV events at the baseline visit, who were followed in rheumatology outpatient clinics at tertiary centres for 7.5 years, were retrospectively analysed to test the performance of the Systematic Coronary Risk Assessment (SCORE), the modified version (mSCORE) European Alliance of Rheumatology Associations (EULAR) 2015/2016, the SCORE2 algorithm (the updated and improved version of SCORE) and the QRESEARCH risk estimator version 3 (QRISK3).ResultsOver 4790 years of follow-up, there were 34 CV events, resulting in a linearised rate of 7.10 per 1000 person-years (95% CI 4.92 to 9.92). The four CV risk scales showed strong correlations and all showed significant associations with CV events (p<0.001). SCORE, mSCORE EULAR 2015/2016 and QRISK3 effectively differentiated between low and high CV risk patients, although the cumulative rate of CV events observed over 7.5 years was lower than expected based on the frequency predicted by these risk scales. Additionally, model improvement was observed when combining QRISK3 with any other scale, particularly the combination of QRISK3 and SCORE2, which yielded the lowest Akaike information criterion (411.15) and Bayesian information criterion (420.10), making it the best predictive model.ConclusionsRisk chart algorithms are very useful for discriminating PsA at low and high CV risk. An integrated model featuring QRISK3 and SCORE2 yielded the optimal synergy of QRISK3’s discrimination ability and SCORE2’s calibration accuracy.

Capillarity, fibre types, fibre cross-sectional areas and perimeters were studied along and across the rat tibialis anterior muscle. The muscle was sectioned at three different levels (proximal, equatorial and distal) choosing five sampling fields for measurements at each level (from anterior to posterior and lateral to medial zones). Significant differences were found in the percentage of fibre types and capillarity between different fields of the same muscle section. Slow oxidative fibres were confined to the posterior muscle zone with a maximum of 3.7%. The posterior fields also had a greater percentage of fast oxidative glycolytic fibres at proximal (72.3%) and equatorial (61.3%) levels, but a lower value at the distal level (44.8%) and lower capillary density counts in total cross-section means (758 vs. 1,069 capillaries/mm 2 in equatorial and 1,035 capillaries/mm 2 at proximal levels). The uneven distribution of both fast fibre types and the different degrees of capillarisation along the muscle are statistically significant and may be due to different biomechanical performances along the rat tibialis anterior. Fibre size was significantly larger at the distal level, but no morphometric differences were found across the section of the same level. At the distal level, the mean total fibre area of fast glycolytic fibres (5,130 μm 2 ) and fast oxidative glycolytic fibres (2,493 μm 2 ) contrasted with values at the proximal (fast glycolytic: 4,070 μm 2 , fast oxidative glycolytic: 1,970 μm 2 ) and equatorial (fast glycolytic: 3,535 μm 2 , fast oxidative glycolytic: 1,714 μm 2 ) levels. The differences along and across the muscle show the need to design a standardised procedure for sample location when performing comparative studies of morphofunctional adaptive changes in skeletal muscle. A significant difference between individuals (animals) in all parameters was evident and should be taken into consideration when analysing the variability: the factor ‘animal’ should be considered in multiway ANOVAs, especially when low sample sizes are used.