A yeast fermentate improves gastrointestinal discomfort and constipation by modulation of the gut microbiome: results from a randomized double-blind placebo-controlled pilot trial.

BACKGROUND: Constipation and symptoms of gastrointestinal discomfort such as bloating are common among otherwise healthy individuals, but with significant impact on quality of life. Despite the recognized contribution of the gut microbiome to this pathology, little is known about which group(s) of microorganism(s) are playing a role. A previous study performed in vitro suggests that EpiCor® fermentate has prebiotic-like properties, being able to favorably modulate the composition of the gut microbiome. Therefore, the aim of this study was to investigate the effects of EpiCor fermentate in a population with symptoms of gastrointestinal discomfort and reduced bowel movements and to evaluate its effect at the level of the gut microbiome. METHODS: This pilot study was performed according to a randomized, double-blind, placebo-controlled parallel design. Eighty subjects with symptoms of gastrointestinal discomfort and constipation were allocated to one of two trial arms (placebo or EpiCor fermentate). Randomization was done in a stratified manner according to symptom severity, resulting in two subgroups of patients: severe and moderate. Daily records of gastrointestinal symptoms were assessed on a 5-point scale, and also stool frequency and consistency were documented during a 2-week run-in and a 6-week intervention phases. Averages over two-week intervals were calculated. Constipation-associated quality of life and general perceived stress were assessed at baseline and after 3 and 6 weeks of intervention. Fecal samples were also collected at these same time points. RESULTS: EpiCor fermentate led to a significant improvement of symptoms such as bloating/distension (p = 0.033 and p = 0.024 after 2 and 4 weeks of intervention, respectively), feeling of fullness (p = 0.004 and p = 0.023 after 2 and 4 weeks of intervention, respectively) and general daily scores (p = 0.046 after 2 weeks of intervention) in the moderate subgroup. A significant improvement in stool consistency was observed for the total population (p = 0.023 after 2 weeks of intervention) as well as for the severe subgroup (p = 0.046 after 2 weeks of intervention), and a nearly significant increase in stool frequency was detected for the total cohort (p = 0.083 and p = 0.090 after 2 and 4 weeks of intervention, respectively). These effects were accompanied by an improvement in constipation-associated quality of life and general perceived stress, particularly in the moderate subgroup. Members of the families Bacteroidaceae and Prevotellaceae, two groups of bacteria that have been previously reported to be deficient in constipated patients, were found to increase with EpiCor fermentate in the severe subgroup. In the moderate subgroup, a significant increase in Akkermansia muciniphila was observed. CONCLUSIONS: Despite the relatively low dose administered (500 mg/day), particularly when comparing to the high recommended doses for prebiotic fibers, EpiCor fermentate was able to modulate the composition of the gut microbiome, resulting in improvement of constipation-associated symptoms. Conversely, the reported increase in bowel movements may have altered the gut microbial community by increasing those groups of bacteria that are better adapted to a faster gastrointestinal transit time. TRIAL REGISTRATION: NCT03051399 at ClinicalTrials.gov. Retrospectively registered. Registration date: 13 February 2017.

Mitigation of heat stress-related complications by a yeast fermentate product.

Heat stress results in a multitude of biological and physiological responses which can become lethal if not properly managed. It has been shown that heat stress causes significant adverse effects in both human and animals. Different approaches have been proposed to mitigate the adverse effects caused by heat stress, among which are special diet and probiotics. We characterized the effect of the yeast fermentate EpiCor (EH) on the prevention of heat stress-related complications in rats. We found that increasing the body temperature of animals from 37.1±0.2 to 40.6±0.2°C by exposure to heat (45°C for 25min) resulted in significant morphological changes in the intestine. Villi height and total mucosal thickness decreased in heat-stressed rats pre-treated with PBS in comparison with control animals not exposed to the heat. Oral treatment of rats with EH before heat stress prevented the traumatic effects of heat on the intestine. Changes in intestinal morphology of heat-stressed rats, pre-treated with PBS resulted in significant elevation of lipopolysaccharides (LPS) level in the serum of these animals. Pre-treatment with EH was effective in the prevention of LPS release into the bloodstream of heat-stressed rats. Our study revealed that elevation of body temperature also resulted in a significant increase of the concentration of vesicles released by erythrocytes in rats, pre-treated with PBS. This is an indication of a pathological impact of heat on the erythrocyte structure. Treatment of rats with EH completely protected their erythrocytes from this heat-induced pathology. Finally, exposure to heat stress conditions resulted in a significant increase of white blood cells in rats. In the group of animals pre-treated with EH before heat stress, the white blood cell count remained the same as in non-heated controls. These results showed the protective effect of the EH product in the prevention of complications, caused by heat stress.

Nerve Transfers in the Management of Femoral Nerve Palsy: A Systematic Review.

ABSTRACT: The primary objective of this systematic review is to describe the effectiveness of nerve transfers for restoring quadriceps motor function in patients with femoral nerve palsy. MEDLINE, EMBASE and CENTRAL were searched from their inception to June 2023 for any English language, primary literature investigating nerve transfers for femoral nerve palsy. Data was extracted for study and intervention characteristics, and clinical outcomes, including preoperative and postoperative knee extension strength, electrodiagnostic studies, functional outcomes, adverse events and donor site morbidity. The primary outcome was defined as return of knee extension equivalent to or greater than a grade 4- on the Medical Research Council scale. Eighteen studies with a total of 40 patients were included. The most common nerve donor was the obturator nerve in 17 studies with 37 patients, followed by the nerve to sartorius in two studies (10 patients). Significant variations in procedures and outcomes reported were observed. There were no studies that reported an effect on ambulation due to donor weakness. Based on the available literature, nerve transfer appears to be an effective treatment for restoring quadriceps function in this population, with 79% of patients in our study achieving at minimum 4-/5 MRC grade power.

Utility of routine post-admission testing for SARS-CoV-2 in a rehabilitation facility.

Asymptomatic screening for SARS-CoV-2 is recommended in healthcare settings during periods of increased incidence, yet studies in rehabilitation settings are lacking. Routine weekly post-admission asymptomatic testing in a rehabilitation facility offered marginal gain beyond syndromic and targeted unit testing and was not associated with a reduced risk of healthcare-associated COVID-19.

Conceptualising the episodic nature of disability among adults living with Long COVID: a qualitative study.

INTRODUCTION: Our aim was to describe episodic nature of disability among adults living with Long COVID. METHODS: We conducted a community-engaged qualitative descriptive study involving online semistructured interviews and participant visual illustrations. We recruited participants via collaborator community organisations in Canada, Ireland, UK and USA.We recruited adults who self-identified as living with Long COVID with diversity in age, gender, race/ethnicity, sexual orientation and duration since initial COVID infection between December 2021 and May 2022. We used a semistructured interview guide to explore experiences of disability living with Long COVID, specifically health-related challenges and how they were experienced over time. We asked participants to draw their health trajectory and conducted a group-based content analysis. RESULTS: Among the 40 participants, the median age was 39 years (IQR: 32-49); majority were women (63%), white (73%), heterosexual (75%) and living with Long COVID for ≥1 year (83%). Participants described their disability experiences as episodic in nature, characterised by fluctuations in presence and severity of health-related challenges (disability) that may occur both within a day and over the long-term living with Long COVID. They described living with 'ups and downs', 'flare-ups' and 'peaks' followed by 'crashes', 'troughs' and 'valleys', likened to a 'yo-yo', 'rolling hills' and 'rollercoaster ride' with 'relapsing/remitting', 'waxing/waning', 'fluctuations' in health. Drawn illustrations demonstrated variety of trajectories across health dimensions, some more episodic than others. Uncertainty intersected with the episodic nature of disability, characterised as unpredictability of episodes, their length, severity and triggers, and process of long-term trajectory, which had implications on broader health. CONCLUSION: Among this sample of adults living with Long COVID, experiences of disability were described as episodic, characterised by fluctuating health challenges, which may be unpredictable in nature. Results can help to better understand experiences of disability among adults living with Long COVID to inform healthcare and rehabilitation.

A dried yeast fermentate prevents and reduces inflammation in two separate experimental immune models.

Diverse and significant benefits against cold/flu symptoms and seasonal allergies have been observed with a dried fermentate (DF) derived from Saccharomyces cerevisiae (EpiCor) in multiple published randomized trials. To determine if DF may influence other immune conditions, two separate animal studies were conducted. Study 1 examined the ability of DF to prevent or reduce inflammation when given orally for 14 days to rats prior to receiving 1% carrageenan (localized inflammation model). DF significantly (P < 0.05) reduced swelling at all time points (1, 2, 3, 6, 12, and 24 hours) versus the control. Edema severity and PGE2 levels were reduced by approximately 50% and 25% (P < 0.05), respectively. Study 2 examined the ability of DF to treat established inflammation induced by type-2 collagen in mice over 4 weeks (autoimmune arthritis model). Significantly reduced arthritis scores, antibody response to type-2 collagen, and interferon-gamma levels were observed compared to controls (all parameters P < 0.05). DF favorably impacts multiple acute and potentially chronic immunologic inflammatory control mechanisms and should be further tested in clinical trials.

Evaluation of different antimicrobial stewardship models at a rehabilitation hospital: An interrupted time series (ITS) study.

Objective: To evaluate different prospective audit-and-feedback models on antimicrobial prescribing at a rehabilitation hospital. Design: Retrospective interrupted time series (ITS) and qualitative methods. Setting: A 178-bed rehabilitation hospital within an academic health sciences center. Methods: ITS analysis was used to analyze monthly days of therapy (DOT) per 1,000 patient days (PD) and monthly urine cultures ordered per 1,000 PD. We compared 2 sequential intervention periods to the baseline: (1) a period when a dedicated antimicrobial stewardship (AMS) pharmacist performed prospective audit and feedback and provided urine culture education followed by (2) a period when ward pharmacists performing audit and feedback. We conducted an electronic survey with physicians and semistructured interviews with pharmacists, respectively. Results: Audit and feedback conducted by an AMS pharmacist resulted in a 24.3% relative reduction in total DOT per 1,000 PD (incidence rate ratio [IRR], 0.76; 95% confidence interval [CI], 0.58-0.99; P = .04), whereas we detected no difference between ward pharmacist audit and feedback and the baseline (IRR, 1.20; 95% CI, 0.53-2.70; P = .65). We detected no statistically significant change in monthly urine-culture orders between the AMS pharmacist period and the baseline (level coefficient, 0.81; 95% CI, 0.65-1.01; P = .07). Compared to baseline, the ward pharmacist period showed a statistically significant increase in urine-culture ordering over time (slope coefficient, 1.04; 95% CI, 1.01-1.08; P = .02). The barrier most identified by pharmacists was insufficient time. Conclusions: Audit and feedback conducted by an AMS pharmacist in a rehabilitation hospital was associated with decreased antimicrobial use.

Long COVID and episodic disability: advancing the conceptualisation, measurement and knowledge of episodic disability among people living with Long COVID - protocol for a mixed-methods study.

INTRODUCTION: As the prevalence of Long COVID increases, there is a critical need for a comprehensive assessment of disability. Our aims are to: (1) characterise disability experiences among people living with Long COVID in Canada, UK, USA and Ireland; and (2) develop a patient-reported outcome measure to assess the presence, severity and episodic nature of disability with Long COVID. METHODS AND ANALYSIS: In phase 1, we will conduct semistructured interviews with adults living with Long COVID to explore experiences of disability (dimensions, uncertainty, trajectories, influencing contextual factors) and establish an episodic disability (ED) framework in the context of Long COVID (n~10 each country). Using the conceptual framework, we will establish the Long COVID Episodic Disability Questionnaire (EDQ). In phase 2, we will examine the validity (construct, structural) and reliability (internal consistency, test-retest) of the EDQ for use in Long COVID. We will electronically administer the EDQ and four health status criterion measures with adults living with Long COVID, and readminister the EDQ 1 week later (n~170 each country). We will use Rasch analysis to refine the EDQ, and confirm structural and cross-cultural validity. We will calculate Cronbach's alphas (internal consistency reliability), and intraclass correlation coefficients (test-retest reliability), and examine correlations for hypotheses theorising relationships between EDQ and criterion measure scores (construct validity). Using phase 2 data, we will characterise the profile of disability using structural equation modelling techniques to examine relationships between dimensions of disability and the influence of intrinsic and extrinsic contextual factors. This research involves an academic-clinical-community partnership building on foundational work in ED measurement, Long COVID and rehabilitation. ETHICS AND DISSEMINATION: This study was approved by the University of Toronto Research Ethics Board. Knowledge translation will occur with community collaborators in the form of presentations and publications in open access peer-reviewed journals and presentations.

Rehabilitation After Critical Illness in People With COVID-19 Infection.

The current COVID-19 pandemic will place enormous pressure on healthcare systems around the world. Large numbers of people are predicted to become critically ill with acute respiratory distress syndrome and will require management in intensive care units. High levels of physical, cognitive, and psychosocial impairments can be anticipated. Rehabilitation providers will serve as an important link in the continuum of care, helping move patients on from acute sites to eventual discharge to the community. Likely impairment patterns, considerations for healthcare practitioner resilience, and organization of services to meet demand are discussed. Innovative approaches to care, such as virtual rehabilitation, are likely to become common in this environment.

Web GIS in practice VII: stereoscopic 3-D solutions for online maps and virtual globes.

Because our pupils are about 6.5 cm apart, each eye views a scene from a different angle and sends a unique image to the visual cortex, which then merges the images from both eyes into a single picture. The slight difference between the right and left images allows the brain to properly perceive the 'third dimension' or depth in a scene (stereopsis). However, when a person views a conventional 2-D (two-dimensional) image representation of a 3-D (three-dimensional) scene on a conventional computer screen, each eye receives essentially the same information. Depth in such cases can only be approximately inferred from visual clues in the image, such as perspective, as only one image is offered to both eyes. The goal of stereoscopic 3-D displays is to project a slightly different image into each eye to achieve a much truer and realistic perception of depth, of different scene planes, and of object relief. This paper presents a brief review of a number of stereoscopic 3-D hardware and software solutions for creating and displaying online maps and virtual globes (such as Google Earth) in "true 3D", with costs ranging from almost free to multi-thousand pounds sterling. A practical account is also given of the experience of the USGS BRD UMESC (United States Geological Survey's Biological Resources Division, Upper Midwest Environmental Sciences Center) in setting up a low-cost, full-colour stereoscopic 3-D system.

Correction to: Immunogenic Yeast-Based Fermentation Product Reduces Allergic Rhinitis-Induced Nasal Congestion: A Randomized, Double-Blind, Placebo-Controlled Trial.

The article ''Immunogenic Yeast-Based Fermentation Product Reduces Allergic Rhinitis-Induced Nasal Congestion: A Randomized, Double-Blind, Placebo-Controlled Trial'', written by Mark A. Moyad, Larry E. Robinson, Julie M. Kittelsrud, Stuart G. Reeves, Susan E. Weaver, Aireen I. Guzman, Mark E. Bubak was originally published electronically on the publisher's internet portal (currently Springer-Link) on 12 August, 2009.

Lessons learned from the 2007-2008 cold and flu season: what worked and what was worthless.

The 2007-2008 cold and flu season had a feeble beginning but a dramatic end. Most states in the U.S. were reporting their highest number of flu cases well into February and March. It is concerning that not only the public but health care professionals have not embraced widespread vaccination because approximately 200,000 hospitalizations and 36,000 deaths a year continue to make this condition one of the leading preventable causes of morbidity and mortality. The real question that needs to be asked next year is who should not be vaccinated rather than who needs to be vaccinated. Preventive measures with soap and water and 62% ethyl alcohol hand gels continue to make sense, whereas the antibacterial soaps seem to provide no added protection and theoretically increase the risk of bacterial resistance. A few dietary supplements garnered some attention. Among products with clinical research, an oral 500 mg qd immunogenic fermentate (Epicor) reduced the risk and duration of cold and flu symptoms in subjects vaccinated for seasonal influenza. Two novel prescription medications (zanamivir [Relenza], and oseltamivir [Tamiflu]) are available for the prevention and/or treatment of influenza and also have demonstrated minimal resistance compared to the older medications. These FDA-approved medications should receive more attention because of their overall effectiveness in treating the flu during the first stages of the disease process.

Effects of a modified yeast supplement on cold/flu symptoms.

A yeast-based product (EpiCor, a dried Saccharomyces cerevisiae fermentate) was compared to placebo to determine effects on the incidence and duration of cold and flu-like symptoms in healthy subjects recently vaccinated for seasonal influenza. In a 12-week, randomized, double-blind, placebo-controlled clinical trial, 116 participants received daily supplementation with 500 mg of EpiCor or placebo for 12 weeks. Data collected included periodic in-clinic examinations and serologic evaluations at baseline, 6- and 12-weeks. Subjects also utilized a standardized self-report symptom diary during the study. Participants receiving the yeast-based product had significantly fewer symptoms and significantly shorter duration of symptoms when compared with subjects taking a placebo.

Neurophysiology contributes to outcome prediction after cardiac arrest.

This "Points of View" paper discusses the role of neurophysiology in predicting outcome in patients who have initially survived a cardiac arrest but remain in coma. The authors, from different clinical backgrounds, discuss their individual approaches to neuroprognostication.

Cholesterol, cholesterol-lowering agents/statins, and urologic disease: Part IV--is vitamin E phosphate or another unique type of this vitamin the last chance for these supplements?

Vitamin E, once the highly espoused heart healthy paradigm of the dietary supplement world, has now been touted by many experts to be either heart unhealthy or simply ineffective based on the results of past and recent randomized trials in cardiovascular medicine. Natural and synthetic vitamin E supplements, especially in large dosages, have been the concern. Researchers have embarked on testing a variety of other novel forms of vitamin E, such as vitamin E phosphate and other forms of vitamin E, to determine safety issues as well as the impact on cardiovascular disease (CVD) risk markers and end-points. Until vitamin E demonstrates meaningful changes in some of the accepted markers of CVD prevention, it will be difficult to espouse their use specifically for these and other conditions.

Anti-inflammatory properties of a dried fermentate in vitro and in vivo.

The aim of this study was to document anti-inflammatory properties of a dried fermentate derived from Saccharomyces cerevisiae (EpiCor(®)), hereafter referred to as dried fermentate in vitro using cell-based bioassays, and in vivo using a skin irritation model in healthy humans. In vitro testing involved parallel assessment of primary human polymorphonuclear (PMN) cell formation of reactive oxygen species (ROS) and migration toward the inflammatory mediator Leukotriene B4. In vivo evaluation used a single-blind placebo-controlled design, where dermal histamine-induced inflammation was used as a model for the complex intercellular signals involved in the initiation, escalation, and resolution of the inflammatory response. Microvascular blood perfusion was evaluated using noninvasive laser Doppler probes applied to the inner forearms of 12 healthy human subjects, where parallel sites were treated with either dried fermentate or saline (placebo). Subjective scores of dermal irritation were also collected. Treatment of PMN cells in vitro resulted in reduced ROS formation and migratory activity toward Leukotriene B4. Clinical results demonstrated significantly reduced microvascular inflammatory responses to histamine-induced skin inflammation, and significantly reduced subjective scores of irritation at the inflamed sites treated with dried fermentate compared with the sites treated with placebo (P<.05). Treatment of inflammatory cells in vitro with dried fermentate resulted in reduced inflammatory responses. This was confirmed in vivo, suggesting that the dried fermentate facilitates the resolution of inflammatory responses. The effects using a topical skin model suggest that similar events may happen when the dried fermentate is introduced across mucosal membranes after consumption.

Diagnosis and Treatment of Work-Related Ulnar Neuropathy at the Elbow.

Ulnar neuropathy at the elbow (UNE) is the second most common entrapment neuropathy after carpal tunnel syndrome and occurs most commonly at the elbow due to mechanical forces that produce traction or ischemia to the nerve. The primary symptom associated with UNE is diminished sensation or dysesthesias in the fourth or fifth digits, often coupled with pain in the proximal medial aspect of the elbow. Treatment may be conservative or surgical, but optimal management remains controversial. Surgery should include exploration of the ulnar nerve throughout its course around the elbow and release of all compressive structures.

A new electromyographic definition of laryngeal synkinesis.

Laryngeal synkinesis involves the misdirected reinnervation of an injured recurrent laryngeal nerve to vocal fold abductor and adductor musculature. The resultant laryngeal dyscoordination can cause vocal fold immobility and airway compromise. Although this entity is sometimes considered in the differential diagnosis, it is only demonstrable with laryngeal electromyography (EMG). We propose a new EMG definition of synkinesis to assist in its identification during workup of vocal fold immobility. A retrospective chart review from 1992 to 1997 in the Voice Disorders Clinic identified 10 patients with laryngeal synkinesis. Five patients had bilateral immobility, and 5 had unilateral immobility. Monopolar EMG was performed on all patients. Fine-wire EMG was performed when monopolar EMG did not elucidate the cause of the immobility. The EMG studies revealed synkinetic reinnervation in all subjects. On the basis of the EMG results, 7 of the 10 patients were treated with botulinum toxin to weaken the undesired reinnervation. Three of the 7 patients had benefit from this therapy. Laryngeal synkinesis should be considered as part of the differential diagnosis of vocal fold immobility. Awake laryngeal EMG is the only method to demonstrate synkinesis of the larynx. The diagnosis of synkinesis is clinically significant in cases of immobility to identify patients who might benefit from botulinum toxin therapy. Additionally, the presence of synkinesis in cases of unilateral immobility may be a contraindication to laryngeal reinnervation procedures. The benefit of botulinum toxin therapy is likely greater in the treatment of bilateral as opposed to unilateral immobility.

Alternative sites for intraoperative monitoring of cranial nerves X and XII during intracranial surgeries.

During intracranial surgeries, cranial nerve (CN) X is most commonly monitored with electromyographic endotracheal tubes. Electrodes on these endotracheal tubes may be displaced from the vocal folds during positioning, and there is a learning curve for their correct placement. Cranial nerve XII is most commonly monitored with electrodes in the dorsum of the tongue, which are also prone to displacement because of their proximity to the endotracheal tube. A retrospective review was conducted of a consecutive series of 83 skull base surgeries using alternative sites for monitoring CN X and XII. On-going (spontaneous) and evoked electromyography (EMG) were obtained from the cricothyroid muscle for CN X and submental genioglossus for CN XII. Stimulation of CN X or XII evoked specific compound motor action potentials from these muscles, and well-defined on-going EMG was observed during tumor resection in the vicinity of CN X and XII. Volume-conducted responses from the adjacent platysma muscle during CN VII stimulation were identified by concomitant responses from the orbicularis oris and oculi. In conclusion, during skull base surgeries, CN X may be monitored with electrodes in the cricothyroid muscle and CN XII with electrodes in the submental genioglossus. These alternative sites are less prone to displacement of electrodes compared with the more commonly used EMG endotracheal tube and electrodes in the dorsum of the tongue. The cricothyroid muscle should not be used when the recurrent laryngeal nerve is at risk.